all

1. Overview of the Course & Syllabus2. Studying the Brain and Behavior

• Disciplines & Approaches3. History of Brain Research

• Cardiocentric vs. Encephalocentric– Hippocrates, Aristotle, Galen, Descartes

• Holism vs. Localization4. Development of Brain Research

• Topographical Organization• Lashley’s Law of Mass Action• Brain Mapping• Dualism vs. Monism

5. Physiological Approach to Consciousness• Blindsight• Split Brains• Unilateral Neglect

PHYSIOLOGICAL PSYCHOLOGY (PSY 254)Lecture 01 (September 08, 2010)

Professor: James R. Moyer, Jr., Ph.D. Semester : Fall 2010Office: Garland 208 Meeting Time: MW 9:00 – 9:50 a.m.Office hrs: MW 10:00 – 10:50 a.m. Meeting Place: ENG 105Office ph: x3255 Psych Listing: 254–402 lectureEmail: [email protected]

Course Description

This course is designed to provide each student with comprehensive exposure to the nervous system and how it governs various behaviors. The course will also cover relevant anatomical, behavioral, psychological, cellular, imaging, and neurophysiological approaches used to study animal behavior. Upon completion of the course, the student will have a solid foundation regarding the biological basis of behavior upon which to build in more advanced courses of study.

Reading Materials

The recommended textbook for this course is Carlson, NR (2010). Physiology of Behavior, 10 th Ed. Allyn & Bacon, New York, NY. (Note: there are a variety of texts on reserve in the library as well).

Course Syllabus for Physiological Psychology

Determination of Your Final Grade

Your overall grade will be determined by combining your scores from the following:

1. Discussion Section Attendance (10%). Discussion sessions will begin Monday, September 13. TA will take attendance. If you cannot make your discussion session, you must make arrangements to attend one of the other 9 discussion sections that week. See page 6 of the syllabus for the weekly discussion session schedule.

2. Weekly Online Quizzes (25%). There will be 12 open-book/notes quizzes available for you to take online beginning September 13 (each quiz will be available for one week). See page 7 of the syllabus for the quiz schedule. NO make-ups (if you fail to take a quiz you will receive a grade of zero for that quiz).

3. Regular Exams (40%). There will be 2 exams (multiple-choice, true-false, matching questions) scheduled during the semester (see dates on syllabus). Exams will be cumulative, which means that there will be some material from the previous exam(s) on each successive exam.

4. Final exam (25%). There will be a cumulative final exam on Tuesday, December 21, 2010 from 10:00 a.m. to 12:00 p.m. in ENG 105. Any student who does not take the final exam will fail the course. The final grade for the course will be determined based on your final average according to the following scale: A = 93-100%; A- = 90-92%; B+ = 87-89%; B = 83-86%; B- = 80-82%; C+ = 77-79%; C = 73-76%; C- = 70-72%; D+ = 67-69%; D = 63-66%; D- = 60-62%; F = 0-59%.


Make-up, Curving and Extra Credit

Make-up exam. Should a student fail to take one of the three scheduled exams during the semester, that student will receive a zero “0” as a grade for that exam. However, at the end of the semester a “one size fits all” cumulative make-up will be offered for students who missed one of the exams (no excuse or reason necessary). The make-up will be held on the study day at 9:00 a.m. on Wednesday, December 15 in ENG 105.

Curving of exams. I will not curve any of the exams. However, all exams will contain some extra credit questions. Thus, it is always possible to score greater than 100% on any exam, including the final.

Extra credit. You may receive up to a maximum of 5 extra credit points, which will be added to your final exam score (thus, if you scored an 86% on the final and you did 5 points worth of extra credit, your final exam score would be a 91%). Check bulletin boards in Garland and Pearse for extra credit opportunities. I will also post some extra credit opportunities on the D2L, if an instructor requests an advertisement in class.


Getting Help

If you are having difficulties or have questions, please do not hesitate to come in for a visit to discuss any issues pertinent to your academic success. If you are struggling in the class, don’t wait until you’ve taken numerous quizzes or both exams to come for help. One mistake students often make is waiting too long to come to me to discuss their performance in the class, which limits my ability to help the student.


Studying the Brain and Behavior

• Neuroscience – multidisciplinary approach to studying the brain

• Behavioral Neuroscience – e.g., psychologists using a bottom-up approach• also Physiological Psychology or Biopsychology

• Cognitive Neuroscience – e.g., psychologists using a top-down approach

• Neuropsychology – e.g., psychologists (top-down) studying higher brain functions and their disorders following brain injury or disease

• also Clinical Neuropsychology or Experimental Neuropsychology

• Computational Neuroscience – utilization of mathematical models to explainhow neuronal activity relates to information processing in the brain

History of Brain Research

CARDIOCENTRIC explanations of behavior prevailed in ancient cultures• argued that the heart controlled thoughts, emotions and behavior• e.g., ancient Egyptians removed and discarded the brain before

mummification but preserved the heart for the afterlife

ENCEPHALOCENTRIC explanations of behavior emerged from dissections• argued that the brain controlled thoughts and emotions and behavior• Hippocrates (460-377 B.C.) after witnessing many dissections argued

that the brain controls behavior• Plato (427-327 B.C.) agreed with Hippocrates• Aristotle (384-322 B.C.) disagreed & argued it “cools the heart”• Galen (130-200 A.D.) later concluded that Aristotle’s role for the

brain was “utterly absurd” for two reasons: 1. The brain was too far away to cool the heart and 2. Too many sensory nerveswere attached to the brain

• René Descartes (1596-1650 A.D.) argued that the pineal gland is the seat of the soul and exerts its actions via pressure changes in the fluid-filled ventricles

Holism vs. LocalizationControlled experiments involving the brain were quite rare until the 19th century. • Thus, two schools of thought emerged regarding the extent to which specific brain areas govern behaviors.

Holism – argued that every area of the brain can control all human functions

Localization – argued that human functions are regulated by distinct brain regions

• Franz Gall (1757-1828) popularized localization based on his theories that specific brain protuberances (felt via skull) corresponded to specific personality traits “Phrenology”

• Although not based on experimental evidence, Gall changed how many people thought about the brain and the work of future scientists supported localization of brain function.

1861 – Paul Broca examined patient “Tan” who had a stroke ~20 yrs earlier.

1876 – David Ferrier stimulated the motor cortex of monkeys and demonstrated that the indicated areas controlled movement of specific body parts:

1 and 2 hind limbs3 tail4, 5, 6 arma, b, c, d hands and fingers7-11 face and mouth12, 13 eyes, head14 ear

1870 – Fritsch and Hitzig stimulated the motor cortex of dogs and noted that stimulation near the top caused the hind legs to wiggle whereas stimulation near the bottom caused the jaw to move.

TOPOGRAPHICAL ORGANIZATION- Motor Cortex

TOPOGRAPHICAL ORGANIZATION- Motor Homunculus

TOPOGRAPHICAL ORGANIZATION- Somatosensory Cortex

1929 – Karl Lashley claimed to have evidence supporting holism

He postulated the following:

1. Law of Mass Action • lesion size rather than location is what matters

2. Law of Equipotentiality • restatement of holism

1940s and 50s – Wilder Penfield used a 3-Volt battery attached to a probe, he stimulated different areas of the cortex in awake patients whose brains were exposed (epilepsy surgery).

He observed the following:

1. Recall of memories when back of cortex was stimulated

2. Sensations in various body parts in response to topographical stimulation of the somatosensory cortex

Penfield’s work inspired the drawings of the homunculi which are used to illustrate topographical organization of the primary motor and somatosensory cortices.

PET scans reveal which specific brain regions are activated by a given task

PET scans reveal which specific brain regions are activated by a given task

Sight Sound

Touch Speech

WHERE’S THE MIND?

Two schools of thought:

Dualism – the mind and body (or brain) are separate.e.g., Plato “father of western dualism”e.g., René Descartes

Monism – the mind is the result of brain functioning & follows physical lawse.g., Leonardo da Vinci (1452-1519) stated “mind is a product of the brain”e.g., most modern brain scientists

Physiological Approaches to Consciousness

• Consciousness can be altered by changes in brain chemistry and thus we may hypothesize that it is a physiological function, just like behavior

• Consciousness and ability to communicate seem to go hand in hand

• Verbal communication allows us to send and receive messages from other people as well as send and receive our own messages (and thus think and be aware of our own existence)

Physiological Approach to Consciousness

1. Blindsight – ability of person who cannot see objects in their blind field to accurately reach for them while remaining “unconscious” of perceiving them (e.g., stroke resulting in damage to the visual cortex)

2. Split Brain operation – surgical cutting of the corpus callosum which connects the left and right hemispheres (to ameliorate the severity of epilepsy)

3. Unilateral Neglect – failure to notice things located to a person’s left (e.g., stroke resulting in damage to the right parietal cortex)

Consciousness is not a general property of all parts of the brain

An explanation of the blindsight phenomenon

MRIs of human brain showing corpus callosum (cc)

corpuscallosum

Identification of an object by smell in a split-brain patient

Identification of an object by sight in a split-brain patient

Angular Gyrus Activity and the Out of Body Experience

END – Lecture 01

ORGANIZATION OF THE NERVOUS SYSTEM• CNS vs. PNS

THE CENTRAL NERVOUS SYSTEM I• Meninges, Ventricles, and Cerebrospinal Fluid• The Spinal Cord• Anatomical Coordinates


Organization of the Nervous System

1. Central Nervous System or CNS • brain• spinal cord

2. Peripheral Nervous System or PNS • outside the spinal cord

The Meninges Line and Protect the CNS

3 Layers:1. dura mater – tough outer layer

1. arachnoid layer – middle vascular layer• serves to return CSF from base of spinal cord

back to brain (and blood stream via arachnoid villi)

2. pia mater – delicate innermost layer

Ventricles & Flow of CSF• Lateral ventricle (2)• Third ventricle – aqueduct of Sylvius• Fourth ventricle – central canal

Flow of CSF (Choroid Plexus Produces CSF)*

*

*

**

*

• CSF flows from choroid plexus (cells that make CSF)• CSF vol ~125 mL, continuously produced with half life ~3 hr• CSF circulates and then returns to blood stream via arachnoid villi or granulations (absorb CSF)

Different Views of the Ventricles & Flow of CSF

CSF Flows Down Spinal Cord via the Central Canal

5 Segments of the Spinal Cord

1. Cervical2. Thoracic3. Lumbar4. Sacral5. Coccygeal

Anatomical Planes

Anatomical Directions

END – Lecture 02

THE CENTRAL NERVOUS SYSTEM IIThe Brain

• Forebrain (prosencephalon)• Midbrain (mesencephalon)• Hindbrain (rhombencephalon)


3 Major Divisions of the Brain

1. Prosencephalon (Forebrain)• telencephalon (cerebrum, limbic system, basal ganglia)• diencephalon (thalamus, hypothalamus)

2. Mesencephalon (Midbrain) – smallest of the 3 divisions• dorsal portion or tectum (superior & inferior colliculi)• tegmentum (red nucleus, periaqueductal gray, substantia nigra)• ventral portion (tracts connecting forebrain & hindbrain)

3. Rhombencephalon (Hindbrain)• metencephalon (cerebellum, pons)• myelencephalon (medulla)

Brain Stem = diencephalon & mesenephalon & rhombencephalon

Prosencephalon (Forebrain) – thinking, creating, speaking, planning, emotions, etc… (pretty much all that makes us human)

1. telencephalon • cerebrum• limbic system (hippocampus, amygdala, septum)• basal ganglia

2. diencephalon • thalamus• hypothalamus

The Cerebrum

Central Sulcus separates frontal (precentral gyrus) from parietal (postcentral gyrus)Sylvian Fissure or Lateral Sulcus separates the temporal lobe from other lobesSulci are fissures or grooves; Gyri are raised areas or outward bumps

The Four Lobes of the Cerebrum

The Major Lobes of the Cerebrum

The Cerebrum

1. Frontal lobes• motor cortex, premotor cortex, prefrontal cortex• prefrontal cortex – executive functions, including short-term

memory, decision making, prioritizing behaviors

2. Parietal lobes• postcentral gyrus, secondary somatosensory cortex• somatosensory cortex processes sensory information

3. Occipital lobes• visual cortex processes visual information

4. Temporal lobes• auditory cortex, olfactory cortex• amygdala and hippocampus (emotions; learning & memory)

Lobes of the Cerebrum

The Cerebral Hemispheres are Connected by:1. Corpus Callosum – connects left and right frontal, parietal, occipital2. Anterior Commissure – connects left and right temporal lobes

(e.g., hippocampus, amygdala)

The CerebrumThe Cerebrum contains:

Gray Matter (5-7 layers of neurons) and White Matter (axons)(the cerebral Gray matter is also called the cerebral cortex)

Cross Section through the Cerebrum

The CerebrumAnterior Commissure

Note that the line from the label “Cerebral Cortex” at the upper left seems to point to white matter. However, the term Cerebral Cortex is generally used to refer to the Gray Matter.

Diffusion Tensor Imaging of Corpus Callosum Projections

Diffusion Tensor Imaging involves a modified MRI magnet. It enables visualization of bundles of axons (the processes that transmit signals from one cell to another)

Prosencephalon (Forebrain) – thinking, creating, speaking, planning, emotions (pretty much all that makes us human)



Limbic System – a circuit of structures involved in emotion and memory(Paul MacLean, 1949)

1. Hippocampus• sea horse shaped structure in temporal lobes• important for forming long-term memories

2. Amygdala• important for emotions• produces fear, aggression• Rabies virus attacks the amygdala

3. Septum• stimulation produces pleasure

4. Mamillary Bodies• hypothalamic nuclei interconnected with hippocampus• important for emotion and memory

Other regions also make up what is called the “limbic system”

Schematic of Limbic Structures

Superior View of Limbic Structures

Side View of Limbic Structures(without any other brain regions)

Basal Ganglia – a cluster of neuronal structures concerned with the production of movement.

1. Putamen and Globus Pallidus• egg-shaped structure in each hemisphere

2. Caudate• tail-shaped structure

Basal ganglia structures are implicated in a variety of disorders, including Obsessive-Compulsive Disorder, Parkinson’s disease, and Huntington’s chorea

Location of the Basal Ganglia & Thalamus

Diencephalon – forebrain region that surrounds the 3rd ventricle

1. Thalamus• a large number of nuclei in each hemisphere• look like flattened egg-shaped structures• relays information to and from the cerebrum

2. Hypothalamus• series of nuclei (located below thalamus)• controls activity of the pituitary gland• important for many regulated behaviors including:

– eating and drinking– sleeping– temperature control– sexual and emotional

Thalamic Connections with the Cortex

Thalamic Connections using Diffusion Tensor Imaging

Location of the Hypothalamus & Pituitary Gland

Location of the Hypothalamus& Pituitary Gland

Mesencephalon (Midbrain) – also contains the reticular formation which runs from hindbrain to forebrain

reticular formation • consists of many nuclei & a diffuse network of

interconnected neurons (reticular = little net) • important in arousal (alerts forebrain to important stimuli) • damage results in a coma

Rhombencephalon (Hindbrain) – immediately superior to spinal cord

1. Cerebellum • located dorsal to both medulla and pons• contains a cortex and underlying white matter• coordination of movement• alcohol impairs cerebellar function

2. Pons • located superior to the medulla• composed mostly of white matter tracts• serves as a bridge between cerebral cortex and cerebellum

3. Medulla• located just superior to spinal cord• ascending & descending cortical tracts cross over from left to right• controls many life-support functions (breathing, HR, coughing, vomiting)

Metencephalon (cerebellum & pons); Myelencephalon (medulla)

Midsagittal view of Forebrain, Midbrain, & Hindbrain

Parts of the Forebrain, Midbrain, & Hindbrain

Human Brainstem

END – Lecture 03

DIVISIONS OF THE PERIPHERAL NERVOUS SYSTEM

1. Somatic vs. Autonomic2. Sympathetic vs. Parasympathetic3. Peripheral Nerves

• Cranial nerves• Spinal nerves

4. Organization of the PNS


Divisions of the Peripheral Nervous System

1. Somatic Nervous System • controls skeletal muscles• under voluntary control

2. Autonomic Nervous System • controls smooth and cardiac muscle• NOT under voluntary control

Divisions of the Autonomic Nervous System

1. Sympathetic Nervous System • fight-or-flight system• dilates pupils• accelerates heart rate• relaxes bronchi• increases blood flow to muscles• decreases blood flow to stomach & internal organs

2. Parasympathetic Nervous System • energy conservation system• constricts pupils• slows heart rate• constricts bronchi• increases blood flow to stomach & internal organs

Divisions of the Autonomic Nervous System

1. Eyes

2. Lungs

3. Heart

4. Stomach, Intestines

5. Blood vessels of internal organs

PNS Transmits Information to the Body via 43 Pairs of Nerves

• 12 pairs of CRANIAL NERVES – enter & exit the brain through holes in skull

• 31 pairs of SPINAL NERVES– enter & exit the spinal cord between vertebrae

CRANIAL NERVES (12 pairs, CNs I through XII)

• enter & exit the brain through holes (foramena) in skull

• permit direct communication between brain & PNS

• allow for sensory input from head, neck, upper abdomen

• allow for motor output from brain to skeletal muscles in head and neck

• allow for parasympathetic output to smooth muscles in head, neck, and upper abdomen

• CNs I & II go to forebrain (prosencephalon)• CNs III & IV arise from midbrain (mesencephalon)• CNs V–XII enter & exit the hindbrain (rhombencephalon)

CRANIAL NERVES (12 pairs)

3 of the cranial nerves serve sensory functions only:

• CN I (olfactory nerve) – sensory; smell • CN II (optic nerve) – sensory; sight • CN III • CN IV • CN V • CN VI • CN VII • CN VIII (auditory nerve) – sensory; hearing • CN IX • CN X • CN XI • CN XII

Red is motor

Blue is Sensory


3 of the cranial nerves control eye movement:

• CN I (olfactory nerve) – sensory; smell • CN II (optic nerve) – sensory; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V • CN VI (abducens nerve) – motor, eye movement • CN VII • CN VIII (auditory nerve) – sensory; hearing • CN IX • CN X • CN XI • CN XII

Red is motor

Blue is Sensory


2 of the cranial nerves control facial muscles:

• CN I (olfactory nerve) – sensory; smell • CN II (optic nerve) – sensory; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V (trigeminal nerve) – motor, chewing; sensory, face & head • CN VI (abducens nerve) – motor, eye movement • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face • CN VIII (auditory nerve) – sensory; hearing • CN IX • CN X • CN XI • CN XII

Red is motor

Blue is Sensory


2 of the cranial nerves control throat and tongue muscles:

• CN I (olfactory nerve) – sensory; smell • CN II (optic nerve) – sensory; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V (trigeminal nerve) – motor, chewing; sensory, face & head • CN VI (abducens nerve) – motor, eye movement • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face • CN VIII (auditory nerve) – sensory; hearing • CN IX (glossopharyngeal) – motor, throat & larynx; sensory, taste • CN X • CN XI • CN XII (hypoglossal nerve) – motor, tongue movements

Red is motor

Blue is Sensory


1 cranial nerve wanders to the head, neck, & upper abdomen:

• CN I (olfactory nerve) – sensory; smell • CN II (optic nerve) – sensory; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V (trigeminal nerve) – motor, chewing; sensory, face & head • CN VI (abducens nerve) – motor, eye movement • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face • CN VIII (auditory nerve) – sensory; hearing • CN IX (glossopharyngeal) – motor, throat & larynx; sensory, taste • CN X (vagus nerve) – motor, smooth muscles of neck, chest & upper

abdomen; sensory, taste, organs of chest & upper abdomen • CN XI • CN XII (hypoglossal nerve) – motor, tongue movements

Red is motor

Blue is Sensory


1 cranial nerve is motor only & innervates neck muscles:

• CN I (olfactory nerve) – sensory; smell (S) • CN II (optic nerve) – sensory; sight (S) • CN III (oculomotor nerve) – motor, eye movement (M) • CN IV (trochlear nerve) – motor, eye movement (M) • CN V (trigeminal nerve) – motor, chewing; sensory, face & head (B) • CN VI (abducens nerve) – motor, eye movement (M) • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face (B) • CN VIII (auditory nerve) – sensory; hearing (S) • CN IX (glossopharyngeal) – motor, throat & larynx; sensory, taste (B) • CN X (vagus nerve) – motor, smooth muscles of thoracic & upper

abdomen; sensory, taste, organs of chest & upper abdomen (B) • CN XI (accessory nerve) – motor only, skeletal muscles of neck (M) • CN XII (hypoglossal nerve) – motor, tongue movements (M)

Mnemonic: Some Say Money Matters But My Brother Says Big Brains Matter More(S = sensory; M = motor; B = both)

Red is motor

Blue is Sensory

The Cranial Nerves & Their Functions

Bell’s Palsy – facial paralysis caused by an infection of the facial nerve (CN VII). Results in paralysis on that side of face (not usually permanent).

PNS Transmits Information to the Body via 43 Pairs of Nerves

• 12 pairs of CRANIAL NERVES – enter & exit the brain through holes in skull

• 31 pairs of SPINAL NERVES– enter & exit the spinal cord between vertebrae

Spinal Nerves Exit the Spinal Cord Between

Adjacent Vertebra

Spinal Nerves Exit the Spinal Cord Between Adjacent

Vertebra

Cross Section of Spinal Cord

1. Sensory is Dorsal (signals enter)2. Motor is Ventral (signals exit the cord)(Bell-Magendie law)

SPINAL NERVES (31 pairs)• enter & exit the spinal cord between vertebrae

• 8 pairs arise from Cervical region (C1–C8)

• 12 pairs arise from Thoracic region (T1–T12)

• 5 pairs arise from the Lumbar region (L1–L5)

• 5 pairs arise from the Sacral region (S1–S5)

• 1 pair arises from the Coccygeal region

(1) For a given region, lower numbers are superior (or higher) along the cord.Thus, C1 is superior to C2, etc…

(2) In spinal cord damage, the higher the lesion on the spinal cord (e.g., C is higher than T or L), the more severe the injury.

5 Segments of the Spinal Cord

1. Cervical2. Thoracic3. Lumbar4. Sacral5. Coccygeal

Dermatome Map• The body area innervated by one spinal nerve

Q: Why do you not see C1 on the dermatome map to the right?

Sacral–Parasympathetic(anus, genitals, & bladder)

Cranial–Parasympathetic(organs, vessels, and muscles, etc…)

Thoracic & Lumbar – Sympathetic(organs, vessels, muscles, anus, genitals, bladder, etc…)

Distribution of the Autonomic Nervous System

• thoracolumbar

• craniosacral

Distribution of the Autonomic Nervous System

END – Lecture 04

NEURONS AND GLIAL CELLS1. Structure of Neurons

• Soma• Dendrites• Axons

2. Classifying Neurons • Anatomical• Functional

3. Glial Cells• Types of Glia• Role in Axon Myelination


The Nervous System

Two Types of Cells: 1. Neurons – cells of the nervous system 2. Glia – support cells

Historically: • 1840 – Schleiden & Schwann proposed cells were basic units of tissue • However, scientists thought that nervous tissue was not made of cells

1860s Golgi – Silver impregnation1892 Cajal – Neuron doctrine

1906 Golgi & Cajal were awarded the Nobel Prize

Camillo Golgi(1843-1926)

Ramón y Cajal(1852-1934)

3 Parts of a Neuron

1. Soma or cell body (contains nucleus, etc…)

1. Dendrite (transmits signals toward soma)• some cells have few dendrites• some cells have many dendrites

2. Axon (transmits signals from soma – output)• all cells have one axon• axon can branch many times

Example of a Motor Neuron

Parts of a Neuron

Information Flow Between and Within Neurons

1. Signal enters dendrite or soma2. Signal travels from soma to axon3. Signal travels down axon4. Signal leaves axon and enters dendrite or soma

Divergence (e.g., sensory) Convergence (e.g., motor)

Information Flow Between Neurons

Basic Subcellular Components of Mammalian cells (similar for neurons)

Structure of Neurons

Major Organelles

1. Nucleus – contains DNA. Gene expression occurs by transcription of DNA into RNA, which is exported out of the cell and used as a template to make proteins.

2. Endoplasmic reticulum – membranous organelle that makes lipids and proteins. There are two varieties observed in cells:

a. Rough ER (studded with ribosomes) - used to make secreted and membrane-bound proteins.

b. Smooth ER (without ribosomes) - used to make lipids.

3. Golgi apparatus – membranous structure that modifies and stores the proteins and lipids made in the endoplasmic reticulum.

4. Mitochondria – fuel powerhouse of the cell. Produces ATP (adenosine triphosphate), which is used as an energy source for chemical reactions.

5. Cell membrane – phospholipid bilayer that surrounds the cell. In neurons, it contains proteins called ion channels that are selectively permeable to various salts or ions (e.g., calcium, sodium, chloride, potassium, etc…).

Cell Nucleus and Protein Synthesis

Chromosomes contain genetic information, 23 pairs– 22 pairs are autosomal– the final pair are sex chromosomes (XX or XY)– the 23 pair of chromosomes contain ~20,000 to 25,000 genes

Genome refers to the sum total of all the genes; same in every cell

Nucleic acids are specialized compounds that contain a nitrogenous base, a sugar, and a phosphoric acid • Deoxyribonucleic acid (DNA) encodes the genetic material of a cell

– found in the nucleus (and in mitochondria) • Contains 4 nitrogen bases: Adenine, Guanine, Cytosine, Thymine • Nucleoside is nitrogen base + sugar (2-deoxyribose) • Nucleotide is base-sugar + phosphoric acid

• Ribonucleic acid (RNA) serves as blueprint for proteins– generally found in the cytoplasm as mRNA and ribosomes– also contain 4 nitrogen bases: Adenine, Guanine, Cytosine, Uracil– triplet base pairs encode specific amino acids (e.g., UGG = tryptophan)– ribosomes read mRNA and add appropriate amino acids to make protein

Examples of Genetic Alterations that affect Brain Function

Fragile-X Syndrome – normally the X chromosome (FMR1 gene has a CGG triad repeated 10-30 times) – in fragile-X, the CGG triad is repeated hundreds of times – produces mental retardation (disrupted synaptic connections)

Mental retardation also results from untreated phenylketonuria (PKU) which is linked to an altered gene on chromosome 12 (lack of phenylalanine hydroxylase)

Down Syndrome – Results from a trisomy of chromosome 21 (3 copies instead of 2) – leads to faulty brain development and cognitive impairments as well as other skeletal and soft tissue abnormalities

Classifying Neurons

1. Based on anatomical or morphological features (Ramón y Cajal) – unipolar (or monopolar) neuron – bipolar neuron – pseudo-unipolar neuron – multipolar neuron

2. Based on functionality (often used to describe neurons in the spinal cord) – motor neuron – sensory neuron – interneuron

Anatomical Classifications

Example of a Sensory Neuron

Note: functionally, this pseudo-unipolar cell contains one axon (on the left) and a sensory process on the right, however this process is functionally an axon (it reliably transmits electrical spikes from the skin to the CNS). Only the sensory endings are technically dendrites.

Warning: some people (including your text) refer to pseudo-unipolar cells as unipolar cells, I maintain a separate classification between these, however both are exclusively sensory neurons.

Functional Classifications

1. Motor neuron2. Sensory neuron

3. Interneuron

Functional Classifications

1. Motor neuron2. Sensory neuron3. Interneuron

Bell-Magendie law – sensory enters dorsal, motor exits ventralNote:

Glial Cells

1. “glue” that holds the nervous system together

1. There are 10 times as many glial cells as neurons– about 100 billion neurons (100,000,000,000)– thus, there are at least 1 trillion glia (1,000,000,000,000)

2. Many are much smaller than neurons

Roles of Glial Cells in the Nervous System

1. Provide nourishment for neuronsAstrocytes surround blood vessels & obtain nutrients

2. Remove waste and dead neurons Astrocytes and Microglia (also function as macrophages)

3. Form scar tissue in the nervous system Astrocytes migrate into empty spaceGliosis is the accumulation of glia in brain tissue

4. Direct development of the nervous systemRadial glia direct neuronal migration

5. Provide axonal myelinationSchwann cells myelinate axons in the PNSOligodendrocytes myelinate axons in the CNS

6. Contribute to blood-brain barrier (fat-soluble enter easily)Astrocytes form tight junctions with capillary endothelium

Glial Cells – Astrocytes

Myelination of AxonsSchwann Cells (PNS)Oligodendrocytes (CNS)

Value of myelination:1. Speeds axonal transmission

(action potential jumps from node of Ranvier to node of Ranvier instead of traveling down entire axon (Saltatory Conduction)

2. Assist in axon regeneration (Schwann cells only)

Electron Micrograph of a Schwann Cell

Schwann Cells – myelinate only one segment of one axon

Comparison of Oligodendrocytes and Schwann Cells

Oligodendrocytes myelinate multiple segments of multiple axons

Blood-Brain Barrier

END – Lecture 05

Parts of a Cell Slides

1. These slides contain background information the majority of which you are expected to know prior to taking physiological psychology.

2. If this material is not familiar to you, please read pages 30-36 of the Carlson text [if you don’t have the Carlson text, similar material is contained in virtually any physiological psychology text (usually in chapter 2 or 3)

Major Organelles

1. Nucleus – contains DNA. Gene expression occurs by transcription of DNA into RNA, which is exported out of the cell and used as a template to make proteins.

2. Endoplasmic reticulum – membranous organelle that makes lipids and proteins. There are two varieties observed in cells:

a. Rough ER (studded with ribosomes) - used to make secreted and membrane-bound proteins.

b. Smooth ER (without ribosomes) - used to make lipids.

3. Golgi apparatus – membranous structure that modifies and stores the proteins and lipids made in the endoplasmic reticulum.

4. Mitochondria – fuel powerhouse of the cell. Produces ATP (adenosine triphosphate), which is used as an energy source for chemical reactions.

5. Cell membrane – phospholipid bilayer that surrounds the cell. In neurons, it contains proteins called ion channels that are selectively permeable to various salts or ions (e.g., calcium, sodium, chloride, potassium, etc…).

Cell Nucleus and Protein Synthesis

Chromosomes contain genetic information, 23 pairs– 22 pairs are autosomal– the final pair are sex chromosomes (XX or XY)– the 23 pair of chromosomes contain ~20,000 to 25,000 genes

Genome refers to the sum total of all the genes; same in every cell

Nucleic acids are specialized compounds that contain a nitrogenous base, a sugar, and a phosphoric acid • Deoxyribonucleic acid (DNA) encodes the genetic material of a cell

– found in the nucleus (and in mitochondria) • Contains 4 nitrogen bases: Adenine, Guanine, Cytosine, Thymine • Nucleoside is nitrogen base + sugar (2-deoxyribose) • Nucleotide is base-sugar + phosphoric acid

• Ribonucleic acid (RNA) serves as blueprint for proteins– generally found in the cytoplasm as mRNA and ribosomes– also contain 4 nitrogen bases: Adenine, Guanine, Cytosine, Uracil– triplet base pairs encode specific amino acids (e.g., UGG = tryptophan)– ribosomes read mRNA and add appropriate amino acids to make protein

Examples of Genetic Alterations that affect Brain Function

Fragile-X Syndrome – normally the X chromosome (FMR1 gene has a CGG triad repeated 10-30 times) – in fragile-X, the CGG triad is repeated hundreds of times – produces mental retardation (disrupted synaptic connections)

Mental retardation also results from untreated phenylketonuria (PKU) which is linked to an altered gene on chromosome 12 (lack of phenylalanine hydroxylase)

Down Syndrome – Results from a trisomy of chromosome 21 (3 copies instead of 2) – leads to faulty brain development and cognitive impairments as well as other skeletal and soft tissue abnormalities

1. How Do Neurons Communicate?• chemical & electrical transmission

2. Chemical Synapse• components of a synapse• types of synapses• neurotransmitters

3. Neuronal Membrane Properties• neuronal cell membrane• membrane potential

• distribution of ions• ion channels• depolarization & hyperpolarization

• action potential4. Signal Integration

• summation• excitation and inhibition


How Do Neurons Communicate?

1. Chemical Transmission• Releasing chemicals onto another neuron

2. Electrical Transmission• Gap Junctions ( electrical coupling between cells)• Propagating signals within a neuron

a) membrane depolarization or hyperpolarizationb) action potential propagation

Synapse – the junction between two connected neurons (Sherrington, 1906)

Synapse is composed of: 1. presynaptic membrane 2. synaptic cleft (<300 Å or 30 nm) 3. postsynaptic membrane

Chemical SynapseDuring an impulse, or action potential, neurotransmitter vesicles fuse with the presynaptic membrane and release neurotransmitters into the synaptic cleft. They then diffuse across the cleft and bind to receptors on the postsynaptic neuronal membrane.

Electron Micrograph of an axodendritic synapse

EM of axodendritic synapse

Mag: 280,000 X

Types of Synapses in the Nervous System

Axodendritic– onto dendrites (a)– onto spines (b)

Axosomatic (c)Axoaxonic (d)DendrodendriticNeuromuscular junction – axon synapses onto muscle cell

How Do Neurons Communicate?

1. Chemical Transmission• Releasing chemicals onto another neuron

2. Electrical Transmission• Gap Junctions ( electrical coupling between cells)• Propagating signals within a neuron

a) membrane depolarization or hyperpolarizationb) action potential propagation

Glial Cells and Neurons can communicate via Gap Junctions

Gap junctions – enable electrical coupling between neurons and/or glial cells

Resting Membrane Potential (RMP)

• Neurons are bathed in a salt solution (the salts dissociate into ions)• Ions are positive (cations) or negative (anions);

e.g., NaCl dissociates into Na+ & Cl-

• Inside cell is more negative• Outside cell is more positive• cell membrane restricts ion movement• RMP is usually ~ -70 mV

Recording Neuronal Activity

Much of what we know about the ionic basis of membrane potential and the action potential was learned using the Squid Giant Axon preparation.

Recording Neuronal Activity

Neuronal Cell Membrane is a Phospholipid Bilayer with Ion Channels

Ions (salts) cannot simply diffuse across the cell membrane (they must go through channels)

Hydrophilic (attracted to water) & Hydrophobic (repelled from water)

High Na+ and Cl- outside (low inside) High K+ inside (low outside)

Distribution of Ions Across the Neuronal Membrane at Rest

What is the Equilibrium or Reversal Potential of an Ion?

Distribution of Ions Across the Neuronal Membrane at Rest

2 forces at work: chemical and electrical gradients

At Rest

During Depolarization

• Neuron’s RMP is negative at rest• During depolarization, Na+ rushes into cell, making inside more positive• If depolarization is strong enough to fire an Action Potential, the inside will become much more positive than the outside

Membrane Potential

• Small inputs are subthreshold (e.g., 1, 2, 3)

• If input is large enough,threshold is reached.

• At threshold, an Action Potential is initiated (e.g., 4)

Relevant Concepts:• All-or-none law• absolute refractory period• relative refractory period

The Action Potential

Summary of Ion Channel Activity During an Action Potential

Summary of Ion Flow During an Action Potential

1. Na+ influx2. K+ efflux3. Overshoot

Conduction of the Action Potential

Movement of an Action Potential down an Unmyelinated Axon

Action Potential Propagation

1. Na+ influx2. K+ efflux3. Spread of depolarization under the

membrane4. Na+ influx …

Saltatory Conduction – conserves energy; increases conduction speed(up to 120 m/s or 432 km/hr)

Myelination

Saltatory Conduction

IMPORTANT CONCEPTS:

• Distribution of Na+ & K+ channels

• Spread of electrical charge

Action Potential Propagation

THOUGHT QUESTION:

Is it better to have a previously myelinated axon become demyelinated or is it better to have an axon that was never myelinated in the first place?

Or do they function the same?

The Na-K Pump (3 Na+ : 2K+) also called the Na-K ATPase

Summary of Action Potential Events1. During AP, Na+ enters2. After AP begins, K+ exits3. Cell must restore Na+ & K+!

Na-K ATPase restores ion balance1. 3 Na+ ions are pumped out 2. 2 K+ ions are pumped in

Coding of Stimulus Strength

1. Temporal summation

2. Spatial summation

How does a neuron integrate or add up inputs it receives?

Temporal and Spatial summation

END – Lecture 06


1. Ion Channels• ligand-gated• voltage-gated• ion-gated • non-gated

2. Ion Channels and Action Potentials3. Neurotransmitter Release at the Terminal Button4. Presynaptic and Postsynaptic Inhibition5. Postsynaptic and Presynaptic Receptors

• ligand-gated Receptors• G-protein linked Receptors

6. Drug Actions on Neurotransmission

Four General Classes of Ion Channels

Ion Channels and Their Functions

Type of Ion Channel

Action

Examples of Function in Neurons

Ligand-gated Neurotransmitters bind with receptors on these channels and open channel

Depolarization (excitation); Hyperpolarization (inhibition)

Voltage -gated Depolarization of cell membrane opens this channel

Propagation of the action potential down the axon; Neurotransmitter release

Ion-gated Increased intracellular concentration of a particular ion opens this channel

Cellular secretion Membrane excitability

Non-gated Always open K+ channels on cell membrane permit K+ to leak out of neuron

Movement of Sodium Ions with Channel Opening

Basic Steps involved in Transmitter Release

Ligand-Gated Ion ChannelA

B

Before the action potential arrives, the postsynaptic ligand-gated channels are closed

After the action potential arrives, neurotransmitter is released, binds and causes postsynaptic ligand-gated channels to open

Schematic of Synaptic Vesicle Release

Steps Involved in Neurotransmitter Release

Neurotransmitter Release & Reuptake

EM of Synaptic Vesicle Release

Summary of Steps Involved in Neurotransmitter Release

1. Action Potential Arrives at axon terminal (Na+ influx)

2. Neurotransmitter vesicle docks at release site

3. The Na+ influx causes depolarization which causes voltage-gated Ca2+ channels to open

4. The Ca2+ influx causes fusion pore to open and vesicle membrane to fuse with axonal presynaptic cell membrane

5. Incorporation of vesicle with presynaptic membrane occurs as neurotransmitter is released

6. Vesicle membrane gets added to axon terminal cell membrane

Membrane Recycling is Essential

1. Synaptic vesicle fusion2. Pinocytosis of membrane3. Cisterna

1. Concentration gradient of Na+ (more out than in) means that Na+ ions flow INTO the cell (and influx of positive charge is depolarization); same for Ca2+ ions. Result is EPSP (excitatory postsynaptic potential)

2. Concentration gradient of K+ (more in than out) means that K+ ions flow OUT of the cell (and an efflux of positive charge is hyperpolarization). Result is IPSP (inhibitory postsynaptic potential)

3. Concentration gradient of Cl- (more out than in) means that Cl- ions flow INTO the cell (and an influx of negative charge is hyperpolarization). Result is IPSP (inhibitory postsynaptic potential)

Why do certain ions/gradients produce EPSPs as opposed to IPSPs?

Movement of Major Ions (EPSPs vs IPSPs)

Postsynaptic and Presynaptic Inhibition

Simple Rule of Thumb (each causes hyperpolarization of the membrane):Postsynaptic inhibition decreases a neuron’s responsiveness to inputs (acts at inputs)Presynaptic inhibition decreases a neuron’s ability to release transmitter (acts at output)

Balance between Excitation and Inhibition

2 Types of Ligand-Gated Receptors

1. Ionotropic Receptors – direct link to ion channel

2. Metabotropic Receptors – indirectly linked to ion channel

IONOTROPIC RECEPTORS(e.g., nicotinic AChRs)

1. Neurotransmitter binds2. G-protein activated3. Adenylate cyclase activated

– converts ATP into cAMP4. cAMP is a second messenger5. cAMP has numerous effects

– e.g., activates kinases which can alter the excitability of different ion channels

METABOTROPIC RECEPTORS(e.g., muscarinic AChRs)

METABOTROPIC RECEPTORS

Effects of Second Messenger Cascades, such as those through metabotropic G-protein-linked receptors, last longer than those through ionotropic ligand-gated receptors.

Agonists and Antagonists

• Agonist activates the receptor

• Antagonist blocks the receptor

Two Common Types of Agonists and Antagonists

DIRECT INDIRECTCompetes for same site as neurotransmitter(competitive)

Does NOT compete for same site as neurotransmitter (noncompetitive)

FIVE WAYS IN WHICH DRUGS CAN AFFECT SYNAPTIC TRANSMISSION

1. Synthesis of the transmitter (1 & 2)

2. Packaging of the transmitter (loading vesicles; 3)

3. Shipping of the transmitter (vesicular release; 4 & 5; 8 & 9)

4. Receiving the transmitter (postsynaptic receptors; 6 & 7)

5. Recycling or destroying the transmitter (reuptake all of part; 10 & 11)

Think in terms of a manufacturing plant that needs raw materials to make the product, needs to wrap it for shipping, needs to ship it, needs someone to receive it, and needs to deal with excess product by destroying or recycling the parts.

SUMMARY OF WAYS IN WHICH DRUGS CAN AFFECT SYNAPTIC TRANSMISSION

Note: AGO = agonist (blue Box); ANT = antagonist (red Box)

END – Lecture 07

PHYSIOLOGICAL PSYCHOLOGY (PSY 254)Lecture 08 (October 04, 2010)

NEUROTRANSMITTER SYSTEMS I1. Neurotransmitters2. Acetylcholine3. The Monoamines

• Dopamine• Norepinephrine• Serotonin

Neurotransmitters and Neurohormones

• Neurotransmitters – substances released by one neuron that bind to receptors on the target neurone.g., acetylcholine

note: some are referred to as Neuromodulators

• Neurohormones – released by brain or other organs, travel via bloodstream to target neuronse.g., epinephrine (adrenal gland)

Neurohormone

Release of epinephrine from the adrenal gland produces sympathetic arousal

Examples of Neurotransmitters in the Brain

1. Acetylcholine 2. Dopamine 3. Norepinephrine4. Serotonin5. Glutamate6. GABA7. Anandamide

Neurotransmitter Associated NeuronsAcetylcholine cholinergicDopamine dopaminergicNorepinephrine noradrenergicSerotonin serotonergicEpinephrine adrenergicGlutamate glutaminergicGABA GABAergicAnandamide cannabinergic

Names of Neurons Associated with Specific Neurotransmitters

Acetylcholine

• First neurotransmitter discovered (in PNS)

• Most extensively studied neurotransmitter

Cholinergic Neurons

1. Dorsolateral Pons ––––––– REM sleep (including atonia)

2. Basolateral Forebrain –––– Activates cerebral cortex (nucleus basalis) facilitates learning & memory

3. Medial Septum ––––––––– Controls rhythms in hippocampus modulates memory formation

Synthesis of Acetylcholine

Produced by combining the lipid breakdown product choline with acetyl-CoA (made in the mitochondria)

Synthesis of Acetylcholine

Enzymes

Enzymes are proteins that catalyze a reaction that might normally take a long time to occur.

If you see a word ending in “–ase” it’s an enzyme. The first word or part of the word (if it’s a one-word name) refers to what the enzyme is acting on.

For example:• Choline acetyltransferase acts on choline to transfer an acetyl group and thus convert it to acetylcholine• Acetylcholinesterase acts on acetylcholine to break it up.

Two Types of ACh Receptors

1. Ionotropic ––– Nicotinic AChRs (fast)

2. Metabotropic – Muscarinic AChRs (slow)

Cholinergic Receptors

• Muscles contain nicotinic AChRs (essential for rapid transmitter action at neuromuscular junction!)

• CNS contains both types, though mostly muscarinic AChRs(nicotinic AChRs tend to be found at axoaxonic synapses)

Breakdown & Local Synthesis of ACh

Acetylcholinesterase – Inactivates ACh after it is released(AChE) (breaks it into acetate and choline)

Choline Re-uptake ––– Choline is transported back into the presynaptic terminal for local synthesis of ACh.

Re-uptake is vital because axonal transport of choline from cell body is slow!

Re-uptake has an efficiency of ~50% (i.e., about half of released is recovered)

Breakdown & Local Synthesis of ACh

Acetylcholinesterase (located inthe synaptic cleft) breaks downacetylcholine into acetate andcholine (which is recycled).

Hemicholinium is a drug thatinhibits the reuptake of choline.

Reuptake has an efficiency of 50%(i.e., 50% is reused)

Drugs that Affect Cholinergic Receptors

Examples

1. Curare• Blocks nicotinic AChRs (or nAChRs) • Had been and still is used by native South American populations • Used to paralyze muscles during surgery

2. Atropine• Blocks muscarinic AChRs (or mAChRs)• Used to treat AChE inhibitors (thus reducing the excess ACh action)• Also used to dilate the pupils for eye exams

Toxins that Affect Cholinergic Transmission

Examples

1. Botulinum toxin ––––––––––––– Clostridium botulinumPrevents release of AChthus it blocks muscle excitationVERY POTENT! (e.g., 1 oz can kill 200 million people!)

2. Tetanus toxin ––––––––––––––– Clostridium tetaniPrevents release of Glycine & GABA thus it blocks inhibitory transmissionindirectly causing excess ACh release

Botulinum and Tetanus toxins cleave Synaptobrevin (thus preventing

vesicle fusion & transmitter release)

Botulinum and Tetanus toxins cleave Synaptobrevin (thus preventing

vesicle fusion & transmitter release)

3. Black Widow Spider Venom ––– Stimulates ACh releaseless toxic, but can be fatal in infants and elderly

Drugs that Affect ACh Breakdown

Acetylcholinesterase inhibitors (AChE inhibitors)• Prolong the effects of ACh release by preventing its breakdown

• Used as insecticides (insects can’t destroy it)

• Used medically to relieve symptoms of myasthenia gravis (auto-immune) e.g., neostigmine - AChE inhibitor that can’t cross blood-brain

barrier

• Used as biological weapons e.g., Sarin, Tabun (treated with atropine sulfate, discussed earlier,

and pralidoxime, which rejuvenates the AChE)

Summary of Cholinergic Drugs

Nicotine Stim nicotinic AChRs AGONIST

Curare Block nicotinic AChRs ANTAGONIST

Muscarine Stim. muscarinic AChRs AGONIST

Atropine Block muscarinic AChRs ANTAGONIST

Black widow spider venom Stim. ACh release AGONIST

Botulinum toxin Block ACh release ANTAGONIST

Neostigmine (can’t cross blood-brain barrier)

Blocks acetylcholinesterase AGONIST

Hemicholinium Blocks choline reuptake ANTAGONIST

Drug Name Drug Effect Effect on Transmission

Classification of the Monoamine Transmitters

Catecholamines IndolaminesDopamine SerotoninNorepinephrineEpinephrine

Synthesis of dopamine (note DA serves as a

precursor for norepinephrine) 1. Tyrosine hydroxylase

2. DOPA decarboxylase

Add –CH3 to the NH2 group to get epinephrine

Dopaminergic Neurons & Projections

1. Substantia Nigra ––––––––– to neostriatum, part of basal ganglia (involved in the control of movement)

2. VTA ––––––––––––––––– to nucleus accumbens (involved in reinforcing effects of drugs of abuse) to amygdala (involved in emotions) to hippocampus (involved in the formation of memories)

3. VTA ––––––––––––––––– to prefrontal cortex (involved in short-term memories, planning, problem-solving strategies)

Nigrostriatal

Mesolimbic projection

Mesocortical projection

MAO (Monoamine Oxidase) – destroys excess monoamines – MAO-B is specific for dopamine – Deprenyl is an MAO-B inhibitor

(depression, Parkinson’s)Reuptake – Transporters are used to remove Dopamine from the synaptic cleft and return it to the nerve terminal

Regulation of Dopamine

Drugs that Affect Dopaminergic Transmission

Examples

1. Monoamine oxidase inhibitors (MAO inhibitors)• MAO regulates production of catecholamines (destroys excess)• MAO inhibitors are used to treat depression• MAO-B is specific for dopamine (e.g., deprenyl)

Also causes release of DA & NE by reversing the direction of transporters

Also blocks voltage-dependent sodium channels

Used to treat ADHD

2. Re-uptake inhibitors• Blocks re-uptake of dopamine by nerve terminals• e.g., amphetamine, cocaine, methylphenidate (Ritalin)

Examples of Drugs that Affect Dopaminergic Transmission

1. L-DOPA• Used to treat Parkinson’s disease• Crosses blood-brain barrier & enters CNS where it is converted to dopamine

2. AMPT (-methyl-p-tyrosine)• Binds to tyrosine hydroxylase• Thus it prevents synthesis of L-DOPA and therefore dopamine

3. MPTP (methyl-phenyl-tetrahydropyridene)• Contaminant in synthetic Heroin• It’s metabolized into MPP+, which destroys dopamine neurons and

produces Parkinson-like symptoms

4. Reserpine• Prevents storage of monoamines in synaptic vesicles• Acts by blocking transporters that pump monoamines into vesicles• End result is no transmitter is released

Effects of Drugs at Dopaminergic Synapses

Dopamine Receptors

• DA receptors are metabotropic

• 5 subtypes of DA receptors (D1 – D5) - D1 & D2 are the most common subtypes

• Some are autoreceptors (similar to D2) located pre- and post-synaptic- postsynaptic – act to decrease neuron firing (K current)- presynaptic – act to suppress tyrosine-hydroxylase

• Apomorphine has multiple effects on DA receptors- At low doses it binds presynaptic autoreceptors (decrease DA)- At high doses it acts as an agonist at postsynaptic D2 receptors

Schizophrenia

• Serious mental disorder characterized by hallucinations, delusions,and disruption of normal logical thought processes

• May involve hyperactivity of dopaminergic neurons (excess)1. Chlorpromazine (D2 antagonist) alleviates hallucinations

in schizophrenic patients2. Clozapine (D4 antagonist) also relieves symptoms

Summary of Dopaminergic Drugs

L-DOPA Stimulate DA synthesis AGONIST

AMPT Inhibit DA synthesis ANTAGONIST

Deprenyl MAO-B inhibitor AGONIST

Reserpine Block storage of DA in synaptic vesicles

ANTAGONIST

Amphetamine,Cocaine,Methylphenidate

All 3 Block DA reuptake AGONIST

MPTP Destroys DA neurons ANTAGONIST

Clorpromazine Blocks D2 receptors ANTAGONIST

Clozapine Blocks D4 receptors ANTAGONIST


Noradrenergic Neurons

Locus Coeruleus (located in Reticular Formation)

• Contains noradrenergic neurons whose axons extend to most of the brain, including thalamus, hypothalamus, limbic, cerebral cortex

• Activation of LC increases vigilance or attentiveness to environment

Norepinephrine

• Synthesized from dopamine

• Synthesis actually occurs inside synaptic vesicles

Synthesis of dopamine and norepinephrine

Add –CH3 to the NH2 group to get epinephrine

1. Tyrosine hydroxylase

2. DOPA decarboxylase

3. Dopamine b-hydroxylase

Examples of Drugs that Affect Noradrenergic Transmission

1. Fusaric acid• Blocks DA--hydroxylase• Results in blockade of NE production in vesicles

2. Moclobemide• Blocks MAO-A (which normally destroys excess NE)• Results in an increase in NE

3. Desipramine• Blocks re-uptake of NE (and possibly serotonin)• a tricyclic antidepressant

Noradrenergic Receptors• NE receptors are called adrenergic because they respond to both norepinephrine

(noradrenalin) and epinephrine (adrenalin)

• Adrenergic receptors are metabotropic and coupled to G proteins

• 2 types of adrenergic receptors are alpha () and beta ()- 1- and 2-adrenergic (located in CNS & PNS) - 1- and 2-adrenergic (located in CNS & PNS)- 3 (located only in PNS)

• 1-adrenergic (slow depolarizing effect; more responsive to excitatory input)

• 2-adrenergic (slow hyperpolarizing effect)

• 1- and 2-adrenergic are excitatory (they increase neuronal responsiveness to inputs). 1 are mostly on heart muscle whereas 2 are mostly on smooth muscle lining bronchioles & arterioles of skeletal muscle.

Example of contraindications: beta-blockers & hypertension in asthmatics!

Summary of Noradrenergic Drugs

Clonidine Stimulate 2 receptors AGONIST

Yohimbine Block 2 receptors ANTAGONIST

Albuterol Stimulate 2 receptors AGONIST

Butoxamine Block 2 receptors ANTAGONIST

Fusaric acid Inhibits NE synthesis ANTAGONIST

Reserpine Inhibits storage of NE in vesicles ANTAGONIST

Desipramine Inhibits reuptake of NE AGONIST

Moclobemide Inhibits MAO-A AGONIST


Clonidine – has a calming effect (but also interferes with learning)Yohimbine – has an agitating effect; promotes anxiety

END – Lecture 08


NEUROTRANSMITTER SYSTEMS II1. The Monoamines (continued …)

• Serotonin2. Amino Acids as Neurotransmitters

• glutamate, GABA, glycine• NMDA receptors & GABA receptors

3. Other Neurotransmitters & Neuromodulators• peptides, lipids, nucleosides, soluble gases

Serotonin

• Synthesized from the amino acid tryptophan

• Important in the following:- regulation of mood- control of eating, sleep, arousal- regulation of pain (hyperalgesia after injury)- control of dreaming

Serotonin

•PRECURSORS to serotonin Dorsal Raphe –– sends 5-HT projections to cortex & basal ganglia

• Medial Raphe –– sends 5-HT projections to cortex & dentate gyrus

Note: raphe means “crease” or “seam” (the nuclei are found near the midline of the brain stem)

The clusters of nuclei that make up the raphe are found in the medulla, pons, and midbrain.

Synthesis of Serotonin (or 5-HT)

PCPA (p-chlorophenylalanine) • blocks tryptophan hydroxylase and thus serotonin production

MAO-A (monoamine oxidase A) • inactivates excess serotonin • ultimately converted into 5-HIAA (measureable metabolite) (5-hydroxy-indoleacetic acid)

Serotonin Receptors

• 5-HT receptors are metabotropic (except 5-HT3 is an ionotropic Cl- channel)

• At least 9 different subtypes of 5-HT receptors- 5-HT1A-1B ; 5-HT1D-1F ; 5-HT2A-2C ; 5-HT3 - 5-HT1B and 1D are presynaptic autoreceptors (axons)- 5-HT1A are presynaptic autoreceptors (soma & dendrites)

• 5-HT3 are important in nausea & vomiting (antagonists help in chemo patients)

Reminder: an autoreceptor is a receptor on its own axon terminal that responds to the neurotransmitter released by the same axon (a negative feedback mechanism)

Drugs that Affect Serotonin

• 5-HT re-uptake inhibitors (SRIs or SSRIs) are useful in treating certain mental disorders (these drugs act by prolonging the action of serotonin at synapses)e.g., Fluoxetine (Prozac) - depression & anxiety disorders

• Drugs that stimulate 5-HT release have also been usede.g., Fenfluramine – has been used as an appetite suppressant (in combinationwith phenteramine which acts on catecholamines to counteract the drowsiness caused by fenfluramine)

• 5-HT2A agonists cause hallucinations e.g., LSD is thought to exert behavioral effects as an agonist of 5-HT2A receptors in the forebrain

• Ecstasy (MDMA; 3-4 methylenedioxymethamphetamine) causes release of serotonin, norepinephrine, and to a lesser extent dopamine (agonistic effect). MDMA damages serotonergic neurons.

Summary of Serotonergic Drugs

Fenfluramine Stimulate 5-HT release AGONIST

Fluoxetine Inhibits reuptake of 5-HT AGONIST

PCPA Inhibits 5-HT synthesis ANTAGONIST

Reserpine Inhibits storage of 5-HT in vesicles ANTAGONIST


Summary of Neurotransmitter Synthesis Pathways

PKU (phenylketonuria) - myelination - brain damage

Amino Acid Neurotransmitters

Two Major Classes: excitatory and inhibitory

1. The Excitatory Neurotransmitter is Glutamate (in brain & spinal cord)

2. The Inhibitory Neurotransmitter is GABA (in brain) or Glycine (in spinal cord and lower brain)


GLUTAMATE (PRINCIPLE EXCITATORY TRANSMITTER)

• 4 receptor subtypes (3 ionotropic & 1 metabotropic)- AMPA receptor (ionotropic) is the most common (Na+ influx). These ionotropic receptors bind glutamate and open ion channel, even when the cell is at rest.- NMDA receptor (ionotropic) is also common but these require depolarization because they are blocked by Mg2+ when neuron is at rest (see next slide).

• caffeine increases glutamate indirectly by blocking adenosine receptors which normally inhibit glutamate release

• MSG (monosodium glutamate) binds glutamate receptors and can produce tingling, burning, ringing in the ears, loss of sensation

NMDA Receptor Channel Complex

6 NMDAR Binding Sites

1. Glutamate (natural agonist)

2. Glycine (co-agonist required for glutamate to have any effect on NMDARs)

3. Mg2+ (binds inside channel and blocks)

4. Zn2+ (decreases activity)

5. Polyamine (increases activity)

6. PCP (blocks channel)

Thus, the NMDA Receptor is a Voltage & Neurotransmitter-Dependent Ion Channel


GABA (MAJOR INHIBITORY TRANSMITTER IN BRAIN)• 2 main receptor subtypes (1 ionotropic & 1 metabotropic)• [discussed further on next slide]

GLYCINE (INHIBITORY TRANSMITTER IN CORD AND LOWER BRAIN)• ionotropic receptors (Cl– influx causes IPSPs)• strychnine is an antagonist (convulsions via excess/uncontrolled excitatatory drive)

GABA Receptors

• Enzyme GAD (glutamic acid decarboxylase) converts glutamic acid to GABA - GAD is inhibited by allylglycine (thus blocking GABA synthesis)

• GABA receptor subtypes:1. GABAA

• ionotropic• opens Cl– channel, causing Cl– influx and hyperpolarization• [see next slide for more details on GABA receptors]

2. GABAB • metabotropic (coupled to G-proteins)• causes K+ efflux and thus hyperpolarization• Baclofen is an agonist (relaxes muscles)

GABAA Receptors

GABAA Receptor has 5 binding sites

1. GABA (natural agonist)• muscimol is a direct agonist• bicuculline is a direct antagonist

2. Benzodiazepine (indirect agonist)• anxiolytic drugs (diazepam or valium)

tranquilizers, promote sleep, reduce

seizure activity, relax muscles

3. Barbiturate (indirect agonist)• low doses have a calming effect• rarely used as anesthetic due to small

therapeutic index (easy to OD)

4. Steroid (indirect agonist)

5. Picrotoxin (indirect antagonist)

Note: -CCM (methyl- -carboline-3-carboxylate) may be a natural ligand for Benzodiazepine binding site. This is an inverse agonist and thus produces fear, tension, and anxiety. It may be part of our fight or flight danger system.

Other Neurotransmitters / Neuromodulators1. Peptides

• 2 or more amino acids linked together• includes various endogenous opioids• Substance P is thought to be the primary neurotransmitter signaling pain

2. Lipids• can transmit between or within cells• e.g., anandamide - endogenous cannabinoid receptor ligand (THC in marijuana binds to the same

receptors); altered mood & sensory perception as well as memory and motor impairments

3. Nucleosides• sugar + purine (A&G) or pyrimidine (C&T) base• e.g., adenosine (ribose + adenine) - coupled to G-proteins which open K+ channels, thus causing

IPSPs (thus it’s inhibitory)• caffeine blocks adenosine receptors and thus is excitatory

4. Soluble Gases• Nitric oxide or NO (NOS converts argenine to NO; blocked by L-NAME)• Carbon monoxide or CO• diffuse out of the cell and activate neighboring cells to produce cGMP

END – Lecture 09


PLASTICITY IN THE NERVOUS SYSTEM1. Neurogenesis 2. Origin of brain cells & brain development3. Axon guidance4. Synaptic pruning5. Axonal regeneration6. Denervation supersensitivity

Development of the Human Brain

Relative Brain Size:At birth: ~ 350 gAt 1 yr: ~1000 gAdult: ~1200 g

• Forebrain• Midbrain• Hindbrain

Timeline of Major Stages in Cerebral Cortex Development

Neurogenesis declines significantly by week 20 and is nearly complete by 5 mo., but it does continue throughout life in some regions (i.e., adult neurogenesis).

Origin of Brain Cells

Neurotrophic factors• EGF (epidermal growth factor) – stem to progenitor

• bFGF (basic fibroblast growth factor) – progenitor to neuroblast

• PDGF (platelet derived growth factor) – progenitor to glioblast (specifically oligodendrocyte)

Brain Development

Processes involved in neuron production:

1. Proliferation – production of new cells (primitive glia & neurons)– stem cells continue to divide

2. Migration – occurs inside out

3. Differentiation & Maturation– formation of axons then dendrites (transplantation depends upon age)

4. Myelination– continues gradually over many years

5. Synaptogenesis – formation of synaptic connections (requires extra cholesterol-from glia)– continues throughout life

Axon Pathfinding(how does an axon know where to go?)

Roger Sperry (1943)

Axon Growth and Neuron Survival

Growth Cones extend out as axons seek targets

Tropic molecules guide axons; produced by targets (e.g., netrins)

Trophic molecules support survival of cells and axons once target is reachedneurotrophins (e.g., NGF, BDNF)

Neuronal and synaptic pruning (via apoptosis)

Important concepts:• Chemoattractant• Chemorepellent

Synapse Pruning (Elimination)

Synaptic connections are plastic!

Effect of Experience on Plasticity

Environmental Enrichment• Increases dendrite complexity• Increases number of synapses

Regrowth of Axons

• Can occur as long as the soma or cell body is intact

• Rate is usually ~1 mm/day (PNS)• in CNS, axons usually regenerate only 1-2 mm total (CNS),

thus paralysis due to spinal cord injury is usually permanent

• In PNS, axon regrowth follows myelin sheath back to target

• Regrowth in PNS may not be perfect• e.g., if a motor neuron’s axon is cut (not crushed),

segments may not align and axon may synapse on wrong target muscle

Collateral Sprouting

Denervation Supersensitivity

Remember:Amphetamine causes DA release from existing axon terminalsApomorphine stimulates DA receptors (an appropriately high dose was used)

END – Lecture 10

MUSCLES & SPINAL REFLEXES1. Muscle Cell Types and Muscle Fibers2. Skeletal Muscles and Movement3. Spinal Reflexes

• Spinal cord• Withdrawal reflex

4. Extrafusual vs. Intrafusal Muscle Fibers• Stretch reflex• Reciprocal innervation• Tendon reflex

5. Crossed Extensor Reflex


Muscles and Muscle Fibers

3 Types Muscle

Muscles and Muscle Fibers

Skeletal Muscle: • Attach to bone or cartilage via tendons • Made up of cells (muscle fibers) • Each muscle fiber contains contractile proteins

Actin – thin filamentsMyosin – thick filaments

• The filaments overlap

Major Components of Skeletal Muscle

Skeletal Muscle: • Striated appearance due to arrangement of actin & myosin • Actin filaments (thin) are attached to proteins that form the Z-line • Myosin filaments (thick) are found between rows of actin

Sliding Filament Theory of Muscle Contraction • During contraction, the following events occur:

1. Actin filaments slide along each myosin filament (from both ends)2. Z-lines get closer together (because actin is attached to Z-line)3. Result is that the muscle shortens

Sliding Filament Theory

Neuromuscular Junction & Muscle Contraction: • Motor neurons innervate skeletal muscle fibers at a special region

called the motor endplate • The motor endplate contains ACh receptors (mostly nicotinic) • One motor neuron can innervate multiple muscle fibers

Motor Unit = motor neuron plus the muscle fibers it innervates • Muscles used for very fine (discrete) movements have smaller motor units • Muscles used for posture have larger motor units

Classification of Skeletal Muscles by Color: Red Muscle

– High concentration of myoglobin (carries oxygen)– Relies heavily on oxidation to produce ATP– Engages in heavy activity without fatiguing– Used for slow, sustained movements– e.g., chicken or turkey legs

White Muscle – Low concentration of myoglobin– Quickly goes into oxygen debt during contraction– Fatigues quickly– Used for rapid contractions in short bursts– e.g., chicken or turkey breasts

Note: In humans and other mammals, red and white muscle fibers are found in the same muscles, unlike birds. For example, sprinting uses white, hiking/walking uses red.

Antagonistic Muscles (flexion and extension)

Isotonic Contraction(muscle shortens)e.g., legs, produces themovement when carrying heavy box

Isometric Contraction(muscle length stays same)e.g., back & arm muscles contract when holding or carrying heavy box

Think of the different musclesthat are used when carrying aheavy box up a flight of stairs – some contractions are isotonicand some are isometric.

Muscular Movements and Contractions

Opposing or Antagonistic

Muscle Movements

Antagonistic Muscles (flexion vs extension)

Spinal Control of Movement

REFLEXES are rapid movements mediated by either brain stemnuclei or the spinal cord (we’ll only cover spinal cord today).

They are very Important (e.g., protect the body, basic life support)

They vary in complexity and number of synapses:• Simple (e.g., withdrawal or flexion reflex)• Complex (e.g., postural, involving many different muscles)

Note: Simple and Complex are relative terms. Even simple reflexes can involve MANY neurons (even thousands).

Three Reflexes Seen in Infants • Grasping • Babinski • Rooting

The Babinski Reflex – in children & adults it’s diagnostic of CNS damage

• Positive Babinski – fanning of toes with stroking bottom of foot– always seen in infants < ~6 mo. (due to lack of descending inhibition)

• Negative Babinski – curling of toes with stroking bottom of foot– seen in older infants and all healthy people– results from descending inhibition from brain

Withdrawal Reflex is a simple reflex involving only a few synapses between the sensory (afferent) neuron and the motor (efferent) neuron

Withdrawal Reflex (involves one or more interneurons between the sensory and motor neuron)

Note: the more interneurons (and thus synapses) there are in the reflex arc, the longer the reflex takes

Withdrawal Reflex

Note: descending projections from the brain can inhibit reflexes

2 Types of Motor Neurons

1. Alpha motor neurons• larger diameter• faster conduction time• innervate extrafusal muscle fibers

2. Gamma motor neurons• smaller diameter• slower conduction time• innervate intrafusal muscle fibers• important for enabling muscle spindle to provide a readout of

muscle length (see gamma motor neuron slide)

Extrafusal fibers run the length of the muscle

Intrafusal fibers do not run the length of the muscle and are located within the muscle spindle

Note that the downward movement of the arm activates stretch reflex, which increases the strength of the muscle contraction and pulls the arm back up

Monosynaptic Stretch Reflex

Monosynaptic Stretch Reflex

Examples• Patellar tendon reflex• Head bobbing upward when falling asleep while sitting in a chair

Intrafusal muscle fibers

Muscle Spindle – A few intrafusal fibers joined to a nuclear bag (inside the nuclear bag is a stretch receptor called the Annulospiral Receptor).

Axons from annulospiral receptor terminate onto motor neurons in spinal cord. Thus, stretching a muscle activates the annulospiral receptor which then

stimulates extrafusal fibers to contract that same muscle.

The Muscle Spindle (or annulospiral receptor) is vital for maintaining muscle tone

Think of it like a “spring” located inside the muscle.

Gamma Motor Neurons

Notice that if the muscle length changes due to muscle contraction (b), the muscle spindle is “off line” and unable to respond to changes in muscle length. Activation of gamma motor neuron contracts the intrafusal fibers and thus “resets” the spindle so it can once again respond to stretch (c).

Problem inherent in the stretch reflex

• Contraction of one muscle would produce contraction of antagonist muscle

• For example, the simple bending of the arm by biceps contraction (agonist) would cause the arm to straighten due to activation of the stretch reflex of triceps (antagonist) muscle

Solution: Reciprocal Innervation (discovered by Sherrington). With reciprocal innervation, the axons of motor neurons that synapse on a muscle also branch and activate interneurons that inhibit motor neurons that synapse on the antagonist muscles.

Reciprocal Innervation

Prevents the simple bending of an arm (biceps contraction) from causing the arm to straighten due to stretch reflex of the antagonistic triceps muscle

What if the muscle is contracting too vigorously?

Golgi Tendon Organ Reflex is activated

Golgi Tendon Organ (GTO) – stretch receptor found in the tendon– provides feedback to nervous system about muscle contraction– GTO fires when stretched– GTO axons synapse onto inhibitory spinal cord neurons– result of GTO activation is inhibition of the motor neuron– prevents damage to muscle as a result of excess contraction

Golgi Tendon Organ Reflex

Think of the GTO like a “spring” located at each end of the muscle (in the tendon)

Proprioceptors(stretch receptors)

Sir Charles Scott Sherrington (1884-1935)• Studied many kinds of reflexes• Discovered reciprocal innervation• Introduced the term synapse• Principle of the Common Path

– motor neuron is final common path for all movement• Principle of the Integrative Action of Neurons

– all neurons in the body work together to produce smooth, precise movement– the crossed extensor reflex is an excellent example

Crossed Extensor Reflex

• Withdrawal Reflex activated by sensory neuron synapsing onto interneuron, which excites motor neurons of the ipsilateral flexor

• Interneuron also crosses over and synapses onto and excites the motor neurons of the contralateral extensor

Example - if you step on a tack while walking, you’ll fall down without this reflex

END – Lecture 11

CONTROL OF MOVEMENT BY THE BRAIN1. Anatomical Considerations

• upper & lower motor neurons• motor cortex

2. Two Major Motor Systems• Pyramidal Motor System (lateral system)

corticospinal tract• Extrapyramidal Motor System (medial system)

basal ganglia & cerebellum

3. Effects of Damage to the Descending Motor System• corticospinal tract damage• basal ganglia and cerebellar damage


Classification of Neurons Associated with the Motor System

1. Upper Motor Neurons • above level of spinal cord motor neurons• e.g., cortical neurons

2. Lower Motor Neurons• spinal cord motor neurons• e.g., those in ventral horn of spinal cord

Motor Cortex & Motor Homunculus

1

2

3

4

Classification of Descending Motor Systems

1. The Lateral Group or System (fine or directed movements)• lateral corticospinal tract (dorsolateral tract)

2. The Medial Group or System (automatic or postural movements)• anterior corticospinal tract (ventromedial tract)• basal ganglia & cerebellum

Contemporary Classification Scheme

The Lateral (Pyramidal) Motor System

Originates in the Primary Motor Cortex (precentral gyrus)

Axons of these Upper Motor Neurons project downward• through internal capsule• through medullary pyramids (hence name) • main branch crosses over at pyramidal decussation in medulla and descends through the contralateral spinal cord forming the lateral corticospinal tract

Lateral Corticospinal Tract

• fine, directed motor control• hands, fingers, feet, toes• synapse directly onto motor neurons or indirectly via interneurons

Effects of Damage to Corticospinal Tract

Damage to the Corticospinal Tract at any Level produces:1. Initial loss of muscle tone (atonia)

• transient flaccid paralysis immediately upon damage2. Hyperactive deep tendon reflexes (myotactic)

• hyperreflexia3. Appearance of the Babinski sign (positive Babinski)

• note: a positive Babinski may be seen during sleep or intoxication, and in infants <~6mo.

Thus, appearance of a positive Babinski sign is diagnostic of pyramidal tract damage.

Effects of Cortical Damage to Lateral System

Damage to the Premotor or Supplementary Motor Cortex or to parts of the Parietal or Temporal cortex produces Apraxia

Apraxia “without action” – Difficulty carrying out purposeful movements, in the absence of paralysis or muscle weakness

Apraxias are classified according to the systems affected:limb apraxia – movement (parietal lobe damage)

(e.g., difficulty if asked to demonstrate a movement)oral apraxia – speech (Broca’s area damage)apraxic agraphia – writing (left parietal lobe damage if right-handed)constructional apraxia - drawing or construction (parietal lobe damage)

(e.g., difficulty with spatial perception and execution)

NOTE: Apraxias DO NOT involve damage to primary motor cortex or any other lower portions of the lateral motor system

Cortical Control of Movement

Posterior association cortex is involved with perceptionsFrontal association cortex is involved with plans for movement

Motor Neuron Disorders

Muscular Dystrophy – muscle wasting • 30 different types, Duchenne’s MD is the most common

- about 1 in 3-4000, typically between ages of 2 and 6- due to defect in gene that encodes dystrophan- more common in boys (due to gene on X-chromosome)

Myasthenia Gravis – degeneration of acetylcholine receptors at NMJ • results from an autoimmune response against AChRs • treated with immunosuppressants or thymectomy • treated with anticholinesterases (acetylcholinesterase inhibitors) • may also try plasmapheresis (filter the AChR-attacking

antibodies from the patient’s blood)

Amyotrophic lateral Sclerosis or ALS (Lou Gehrig’s disease) – motor neuron degeneration • degeneration of motor neurons in brain and spinal cord • progresses from muscle weakness to muscle wasting • no treatment • ~5,600 new cases each year, typically between ages of 40 & 70

The Medial (Extrapyramidal) Motor System

Coordinates gross movements & postural adjustments

• Develops before the pyramidal (lateral) systeme.g., babies can play patty-cake before learning to hold a crayon

• Develops at different timese.g., babies can hold head up before sitting upright

The Medial (Extrapyramidal) Motor System

Brain Regions

1. Cerebellum• Receives sensory information from all sensory systems and cortex • It must know what every muscle in the body is doing at every moment• Ballistic movements, learned movements

2. Basal Ganglia • Relays info to and from cerebral cortex• Numerous structures work together to coordinate gross movements

Some drugs (e.g., classical antipsychotics) act to decrease dopamine activity in the brain. Thus, these drugs may have “extrapyramidal side effects”, which include tremors, rigidity, and a shuffling gait

The Cerebellum and Movement

Note: The cerebellum may contain ~50 billion neurons, compared with ~22 billion neurons in the cerebral cortex!

• important for rapid coordination of movements

• important for ballistic movements

• receives information from all senses and cerebral cortex

• must know what every muscle is doing at any given time in order to properly coordinate rapid movements

• damage results in a variety of impairments:ataxia – inability to walk in a coordinated manner

disequilibrium – loss of balance

Basal Ganglia – a cluster of neuronal structures concerned with the production of movement.

1. Striatum (Caudate, Putamen)• receives information from cerebral cortex• sends that information to Globus Pallidus• caudate – process of cognitive information• putamen – relays motor signals

2. Globus Pallidus• sends information back to cortex via thalamus

3. Substantia Nigra• produces DA and projects to caudate and putamen

4. Subthalamic Nucleus (STN)• sends projections to and receives projections from the globus pallidus

Location of the Basal Ganglia within the Forebrain

Damage to the Basal Ganglia

Basal ganglia damage results in movement disorders

Tics – brief, involuntary contractions of specific musclesChoreas – involuntary movements of head, arms, legs

Huntington’s disease– uncontrolled tics and choreas early, dementia later– disruption of gene on chromosome 4 (excess CAG repeat) resulting in an abnormal Huntingtin (Htt) protein (with an elongated string of glutamine

residues on it). The Htt mutation ultimately leads to death of GABAergic inhibitory neurons in the putamen (part of striatum)

Parkinson’s disease– tremor, loss of balance, rigidity (hard to initiate movement)– caused by loss of dopaminergic neurons in substantia nigra

Relationship Between CAG Repeats and Age of Onset

• CAG codes for glutamine• 11-24 CAG repeats is normal• >36 is linked to Huntington disease

Brain of Patient with Huntington’s Disease

Treatments for Parkinson’s Disease

1. Pharmacological Treatments L-DOPA – crosses blood-brain barrier and is converted to dopamine glutamate antagonists – reduce hyperactivity of glutamate in subthalamic nucleus

2. Destructive Surgical Treatments thalamotomy – surgical cut in ventral thalamus pallidotomy – surgical cut through the globus pallidus

• both are thought to interfere with excitatory messages that produce symptoms• both reduce the rigidity and tremors (improving posture, gait, locomotion)• cognition and mood may also be improved with pallidotomy

3. Nondestructive Surgical Treatments subthalamic nucleus (STN) stimulation reduces symptoms

• also called deep brain stimulation

4. Restorative Surgical Treatments fetal stem cell implantations – insertion of DA-producing cells from dead fetuses

• raises serious ethical issues (adult stem cells may be better, especially from same patient) gene therapy – introduction of a gene that would rescue function

• e.g., use virus to deliver GAD gene to STN, thus restoring lost inhibition

END – Lecture 12

THE VISUAL SYSTEM I1. Electromagnetic Spectrum & Waves2. Anatomy of the Eye3. Eye anatomy and blindspot4. Visual Receptors

• rods• cones

5. Cells of the Retina6. Effects of light stimulation on transmission through retina


Many Stimuli are Transmitted as Waves (e.g., electromagnetic radiation, vibration, and sound)

The ElectromagneticSpectrum

1. Wavelength (nm, 1 nm = 10-9 m)2. Frequency (Hz, Hertz, cycles per s)3. Amplitude (dB, decibels, range: 0 to 160)

Wavelength~380-760 nm is visible to humans

Q: Why is the sky blue during day but reddish at sunrise or sunset?

v = ƒ

Electromagnetic Radiation (e.g., Light Waves)

Relationship between velocity (v), frequency (ƒ), and wavelength () of light can be described by the following equation:

• Don’t worry about doing any calculations, this is just an example

e.g., blue light with a wavelength of 455 nm (455 x 10-9 m) would have a frequency of:

ƒ = v / ƒ = (3 x 108 m/s) / (455 x 10-9 m)ƒ = (3/455) x 1017 / secƒ = .00659 x 1017 Hzƒ = 659 x 1012 Hz

Notes: speed of light (v) is 3 x 108 m/s or 186,000 miles/secm = meters; s = secondsnm = nanometers (10-9 meters)

Stimulus Intensity is encoded by changes in action potential frequency

Adaptation is a decrease in the firing rate in response to a continuous stimulus (e.g., odor perception decreases as you get used to it)

Distribution of Visual Receptors

Why is this baby owl’s head nearly upside down?

The Visual System

Cornea – transparent covering in front of eye, curvature aids in focusing light

Aqueous humor – fluid behind cornea

Pupil – opening in center of iris

Lens – transparent structure that focuses images on retina• controlled by ciliary muscles (smooth muscle)• when image is far away, the lens flattens (gets thinner/weaker)• when image is close, the lens shortens (gets fatter/stronger)• process of lens changing shape is accommodation• presbyopia is age-related loss in lens elasticity (need reading glasses)

Vitreous humor – clear gelatinous liquid inside main part of eyeball

Retina – interior lining of the back of the eye• contains photoreceptors (rods and cones)

Optic Nerve – carries visual signal from retina into the brain

Anatomy of the Eye

Anatomy of the Eye

• Optic Axis- imaginary straight line through eye to fovea centralis

• Fovea Centralis- cones only (no rods are in fovea!)- the highest density of rods is in the area right next to the fovea (rods decrease in density with distance from fovea)

• Optic Disk- where optic nerve exits- blind spot

• Sclera- tough outer white covering

Right Eye

Blindspot on the Retina(due to optic nerve exiting eye)

Blindspot is due to the Optic Disk

Self Test: (1) Draw 2 objects about 2 inches apart. (2) Close left eye. (3) Hold paper at arms length and focus on the left (medial) object with right eye. (4) Slowly move paper closer. (5) The right (lateral) object will eventually disappear.

1. Rods - respond best to dim light (black & white)• 1 kind of rod• more numerous than cones (~120 million rods)• dispersed throughout the retina• insensitive to detail; peripheral vision• extremely sensitive to light (best in dim light)

“scotopic or dark vision”

2. Cones - respond best to bright light (color)• 3 different kinds of cones• less numerous than rods (~5 million cones)• concentrated in fovea centralis (macula)• fine detail• less sensitive to light (best in bright light)

“photopic or light vision”

Visual Receptors

Visual Receptors

1. Outer Segment - photopigments• e.g., rhodopsin (rods)• photopigments absorb photons (light)• 2 parts: protein opsin & lipid retinal• 11-cis-retinal (benefits of Vitamin A)• bleached after absorption of photons• unbleached after removal of light

(called dark adaptation)

2. Inner segment - nucleus & organelles

isomerization

Visual Receptors

Bleaching of Photopigments

Rods – very sensitive to light (thus sensitive to bleaching)• photopigments bleach faster and more completely than cones

Cones – less sensitive to light• photopigments bleach more slowly• if light is bright enough, even cones will bleach

e.g., sun reflecting off snow is blinding

Note: when a photoreceptor absorbs light, it is bleached (unresponsive to light). Following removal of light, recovery (unbleaching) occurs and photoreceptor is ready to respond to light once again. This unbleaching is called dark adaptation.

5 Layers of Cells in the Retina (listed from the back or outer layer of the eye)(only worry about the 3 main layers, highlighted blue)

1. Visual receptors – Located near the back outer layer of retina, just in front of the pigment epithelium. They absorb photons (light waves).

2. Horizontal cells – (don’t worry about these!)

3. Bipolar cells – transfer generator potentials from visual receptors to ganglion cells.

4. Amacrine cells – (don’t worry about these!)

5. Ganglion cells – Located just behind the vitreous humor and fire action potentials. Their axons form the optic nerve.

Pigment epithelium back layer of cells that contains blood vessels that nourish the retina and also serves to absorb stray photons (thus minimizing distortion).

Other mammals (dogs, cats, deer, cattle) lack a pigment epithelium but instead they have a reflecting tapetum that is important for night vision (reflects light to make maximal use in dim light conditions).

3 Main Layers of the Retina

Retina

(1) Visual receptors – in the dark, rods and cones are depolarized and release inhibitory transmitter onto bipolar cells (hyperpolarizing them). Light closes ion channels that are permeable to Na+, results in hyperpolarization of visual receptors and less transmitter release, thus depolarizing bipolar cells .

(2) Horizontal cells – inhibit nearby visual receptors in response to activation by light (lateral inhibition which enhances contrast between edges. (Don’t worry about these!)

(3) Bipolar cells – transmit between visual receptors and ganglion cells (releases excitatory transmitter glutamate onto and activates ganglion cells)

(4) Amacrine cells – provide feedback to bipolar and ganglion cells (Don’t worry about these!)

(5) Ganglion cells – just behind the vitreous humor and fire action potentials. Their axons form the optic nerve.

Retina

1. Normally the visual receptor is depolarized and inhibiting the bipolar cell.

2. Light hyperpolarizes the visual receptor (rods or cones) which then depolarizes the bipolar cell.

3. Depolarization of the bipolar cell causes depolarization of the ganglion cells.

4. Depolarization of the ganglion cell causes it to fire more action potentials.

5. Net Result is that light shining on the photoreceptor excites the ganglion cells

Summary of the Effects of Light Stimulation

Effects of Light on Retinal Circuitry (Summary)

-30 –-50 –-70 –-90 –

Mem

bran

e po

tent

ial (

mV

)

END – Lecture 12

THE VISUAL SYSTEM II1. Transmission of visual information through brain2. Color vision

• Trichromatic color theory• Opponent-process theory

3. Disorders of the visual system


Transmission of Visual Information Through the Brain

Retina

Optic Nerve(CN II)

Optic Chiasm(nasal hemiretina crosses over)

1° Visual Cortex(Occipital lobe)

Visual Association Cortices(Occipital, parietal, temporal)

Lateral Geniculate(Thalamus)

Superior Colliculus(Mesencephalon)

Optic Tract

(Blindsight)

Main PathSC processes the location of objects

Minor Path

Receptive Field & Visual Acuity

Images on retina are upside down and backwards

Color Vision

Young-Helmholtz or Trichromatic Color Theory (1802)

• Proposed independently by Thomas Young and Hermann von Helmholtz• Only 3 different color receptors (cones) are needed to see all shades of color

3 Different cones

• S-Cones (Short wavelength or Blue) - excited by Blue light• M-Cones (Medium wavelength or Green) - excited by green light• L-Cones (Long wavelength or Red) - excited by red light

Light Mixing and Pigment Mixing

Color Vision

For Normal Color Vision, all 3 Cones are Needed:

Trichromats – have all 3 functional cones: S, M, L– normal color vision

Dichromats – only have 2 functional cones: S, M or S, L (e.g., either M or L is nonfunctional)

Monochromats – only have 1 functional cone– can only see black, white, and grays

Note: Other mammals (and some non-human primates) are Dichromats, and have only two types of cones: S and LM (intermediate cones that respond to yellow light).

Certain color-deficiencies occur most commonly in males (XY) because the genes for cones are on the X-chromosome (usually the defective gene is rescued in females by a normal X-chromosome)

Color Deficiencies (Red-Green) - Ishihara Test

NORMAL Color VisionA B C

Top 25 45 6Bottom 29 56 8

RED-GREEN Color BlindA B C

Top 25 spots spotsBottom spots 56 spots

A B C

1878 – Ewald HeringOpponent Colors

Red–greenBlue–yellowWhite–black

1878 – Ewald HeringOpponent-Process Theory (explains negative afterimage and why we can’t imagine “reddish-green” or “bluish-yellow” colors)

How Individual Ganglion Cells Code for Color}

Negative Afterimage

Opponent-Process Coding

Summary of Opponent-Process Color Coding

1. Red light activates Red Cone which activates Red-Green ganglion cells.• Result is Red

2. Green light activates Green Cone which inhibits Red-Green ganglion cells.• Result is Green

3. Yellow light activates Red & Green Cones equally. The Red Cone activates both Red-Green and Yellow-Blue ganglion cells. The Green cone (1) inhibits the Red-Green ganglion cell (thus canceling activation by red) and (2) activates the Yellow-Blue ganglion cell.

• Result is Yellow (red is canceled by activation & inhibition)

4. Blue light activates Blue Cone which inhibits Yellow-Blue ganglion cells.• Result is Blue

Retinex TheoryBoth the cerebral cortex and retina work together to determinebrightness and color perception.

Example: afterimage of an illusion

Visual Illusion – What colors do you see?

Cornea (smooth, transparent covering of front of eyeball)• Any scratches or damage will create distortions of light passing

through to the retina and can cause astigmatism.• Astigmatism - blurring of objects in certain orientations

Aqueous Humor (clear liquid between lens and cornea)• shape of eyeball is maintained by pressure and aqueous humor

drains fluid via ducts. If ducts clog, excess pressure builds up.• Glaucoma - damage to optic nerve due to excess pressure

leading cause of blindness in the U.S.

Disorders of the Visual System: Eye

Lens (elastic, transparent structure that focuses light onto the retina)

• Presbyopia - age-related inability of lens to fatten (less elasticity), which impairs ability to bring close objects into focus

• Cataract - lens becomes opaque with age (UV damage). Light cannot pass and vision is disrupted. Surgical removal of lens and replacement with a monofocal lens (usually a flat lens to allow distant focus only, so glasses would be required for near objects). Multifocal lenses are available too.Prevention? Sunglasses.

• Myopia (nearsighted) - lens focuses distant objects in front of retina (eyeball too long or lens too strong), but vision for near objects is intact.

• Hyperopia (farsighted) - lens focuses near objects behind retina (eyeball too short or lens too weak), but vision for distant objects is intact.


Retina (multi-layered structure containing photoreceptors)

• Macular degeneration - degeneration of macula lutea (area that contains the fovea & thus cones). Symptoms: loss of ability to see detail or even read. Eventually spreads to all photoreceptors and blindness results.

• Retinitis pigmentosa - genetic disorder (chromosome 8) affecting rhodopsin (rods). Symptoms: night blindness, tunnel vision. Eventually, disease spreads to cones - total blindness.

• Diabetes can produce blindness due to weakening of blood vessels lining the retina (resulting in bleeding into vitreous humor, as well as oxygen and nutrient deprivation).


Emmetropia

Myopia

Hyperopia

Focusing of Distant and Near Sources

It takes a stronger lens (accommodation) to focus a near image at the same distance that it takes a weaker lens to focus a distant image (compare a and c).

Thus, the human lens accommodates (gets fatter or stronger) in order to properly bring a near object into focus on the retina.

Note: the rays from a distant source are essentially parallel (a) whereas the rays from a near source are still diverging (b & c). Thus, without changing lens shape - e.g., without getting fatter (as in c) - the near source would fall beyond the focal point (b) of the distant source.

END – Lecture 13

THE VISUAL SYSTEM III• Visual Pathways from Retina to Cerebrum

• The Parvocellular or Ventral Stream the “what” system

• The Magnocellular or Dorsal Stream the “where” system

• Disorders of Visual Processing

• Types of Cells in Visual Cortex


Ganglion Cells LGN V1

Note: The Ganglion Cell to LGN pathway is actually 2 pathways (parvocellular & magnocellular)

Two Kinds of Ganglion Cells Project to Separate Layers of LGN(and thus different Targets in V1)

1. Large Ganglion Cells or Magnocellular• from rods• 10% of ganglion cells• project to LGN layers I-II (e.g., bottom 2 layers)• V1 target is interblob region• origin of the “where” or dorsal system• processes form, motion, spatial relations

2. Small Ganglion Cells or Parvocellular • from cones

• >80% of ganglion cells• project to LGN layers III-VI (e.g., top 4 layers)• V1 target is blob region (cytochrome oxidase-rich)• origin of the “what” or ventral system• processes color, form, detail

LGN (thalamus)

6 layers:

Top 4 layers (L3–6) • parvocellular layer • from cones • 2 layers from left eye • 2 layers from right eye

Bottom 2 layers (L1–2) • magnocellular layer • from rods • 1 layer from left eye • 1 layer from right eye

Thus, each layer of LGN only receives monocular information (from one eye or the other).

Parvo

Magno

Brodmann’s Area 17 is Primary Visual Cortex

Brodmann used microscopicappearance to classify brainregions

Primary Visual Cortex (V1) is located in the Occipital lobe and corresponds to Brodmann Area 17

Two Streams of Visual Information Flow

Two Streams of Visual Information Flow

1. Dorsal “where”• magnocellular• from rods

2. Ventral “what”• parvocellular• from cones• well-developed in

primates

Mapping the Visual Field onto V1 (Primary Visual Cortex)

Disorders of Visual Processing

1. Damage to V1• if tiny, Scotoma (blind spot)• if in one hemisphere, Hemianopia (blind in contralateral visual field)• if complete and bilateral, Blindness results (may exhibit blindsight)

2. Damage to V2 and V3• hard to exclusively damage with damaging V1, usually blindness

3. Damage to V4• unable to see, perceive, or even remember seeing colors (achromatopsia)

4. Damage to V5• unable to perceive movement or moving objects (akinetopsia)

Disorders of Visual Processing

5. Damage to IT (Inferior temporal cortex) Creates family of disorders called visual agnosia (can’t recognize familiar objects)

• Prosopagnosia (cannot recognize familiar faces)- results from damage to right IT alone or from bilateral IT damage- particularly damage to the fusiform gyrus (fusiform face area)

• Can have visual agnosia without prosopagnosia- thus object recognition areas are not the same as face recognition areas

• Pure alexia (cannot put letters together but can recognize individual letters)- results from damage to left IT cortex

6. Damage to Posterior Parietal cortex Creates disturbances in ability to locate and reach for objects

• Balint’s syndrome - difficulty perceiving more than one object at the same time (simultanagnosia)- can’t scan environment and fixate on objects - difficulty with visually-guided hand movements (optic ataxia)- results from bilateral damage to posterior parietal cortex

• Visual extinction - ignore object in visual field contralateral to damaged area- usually results from unilateral damage to right posterior parietal cortex

Fusiform Face Area(IT cortex)

Visual Object Agnosia(w/o prosopagnosia)

Activation of Fusiform Face Area by Faces (e) and Blurry Shapes in the appropriate position (a)

Damage to Posterior Parietal Cortex(unable to visually localize objects)

END – Lecture 14

THE SOMATOSENSORY SYSTEM I1. Somatosensory system and receptors

2. Anatomy of the Somatosensory Pathways• Types of axons carrying somatosensory information• Lemniscal path• Spinothalamic (or extra lemniscal) path

3. Somatosensory Processing “What” & “Where” Systems

4. Somatosensory Plasticity• Phantom limb pain

PHYSIOLOGICAL PSYCHOLOGY (PSY 254)Lectures 15 (November 1, 2010)

The Somatosensory System

• What are Somatosensory Receptors?- various types of receptors in the skin- various types of receptors in muscles, tendons, and joints

• What is Kinesthesia?- ability to sense movement

• What is Proprioception?- ability to know where a body part is in 3D space

• What is Interoception?- sense that arises from the internal organs (e.g., receptors in smooth muscle)

Kinesthesia & Proprioception work together to create body image.


• Most Somatosensory Receptors are mechanoreceptors• e.g., annulospiral receptors (muscle spindles) and GTOs (tendons)• pressure and vibration activate mechanoreceptors in the skin

• Temperature changes activate both mechanoreceptors and chemoreceptors• expansion and shrinking of skin with temperature (mechano)• cold sensors and warmth sensors exist (carried by different types of axons)• Transduction is via Transient Receptor Potential family of proteins (called TRP receptors)

- some TRP receptors respond to chemicals (e.g., menthol, in mints, feels cool)

Pain information can be carried via both mechanoreceptors and chemoreceptors• e.g., excess pressure on skin (mechano)• e.g., bradykinin and prostaglandin release from bee sting (chemo)

Somatosensory Receptors include both mechanoreceptors and chemoreceptors

Types of Receptors in the Skin (only focus on these 4)1. Pacinian Corpuscles (PRESSURE & VIBRATION)

Sensory fiber surrounded by concentric layers (located deep, below dermis)

2. Meissner’s corpuscles (TOUCH)Composed of axonal loops, separated by nonneuronal support cells Important for detecting movement along skin (e.g., adjusting grip)

3. Basket endings (MOVEMENT OF HAIR)Wrapped around individual hairs and detect movement

4. Free nerve endings (PAIN or TEMPERATURE)Single, bare nerve endings at end of sensory fiber


There are others, such as the following (but don’t worry about these)• Ruffini’s endings (STRETCH) (& WARMTH?)

Sensory fibers terminate among collagen fibers in skin• Krause endbulbs (COLD?)• Merkel’s disks (TOUCH, RESPOND TO SUSTAINED PRESSURE)


Two Types of Axons Carry Sensory Information to the CNS

1. A-fibers (large myelinated axons; 3 types)A (alpha) are large diameter (15-20 µm)

most heavily myelinated & fastest (100 m/s or ~224 mph) axons of muscle spindles & GTOs

A (beta) are medium diameter (5-15 µm) well-myelinated & fast (50 m/s) axons of Pacinian & Meisner’s corpuscles and Merkel disks

A(delta) are small diameter (1-5 µm) poorly myelinated & slower (10-30 m/s) some pain & pressure cold sensors (temp)

2. C-fibers (very small diameter axons, <1 µm) unmyelinated axons & slow conduction (0.4-2 m/s) axons of free nerve endings (pain or nociception) most numerous (~80% of axons terminating in the skin) warmth sensors (temp)

General Rule of Thumb

1. Info about pressure & touch travels to the brain quickly(more recent system)

2. Info about pain & temperature travels to the brain more slowly (older system)

1. Lemniscal Path (A-fibers)• ascends dorsal column• crosses over in medulla• processes precise touch & kinesthesia

2. Spinothalamic Tract (C-fibers)• crosses over in spinal cord• processes pain & temperature

Somatosensory Paths from the Body to the Cortex

All paths go through ventral posterior thalamus

Somatosensory Paths from the Body to the Cortex

Lemniscal (touch)• crosses over in hindbrain

Spinothalamic (pain)• crosses over in cord

Somatosensory Paths from the Face & Head to the Cortex

The “Trigeminal System or Pathway”via Cranial Nerve V (Trigeminal nerve)

Primary Somatosensory Cortex is topographically organized

Remember – Fine touch & pressure go via lemniscal pathPain & temperature travel up the spinothalamic tract


1. “What” System – What is the perceived sensation?• Inferior Parietal Cortex

Damage to Inferior Parietal Cortex produces Tactile Agnosia an inability to recognize objects through touch

2. “Where” System – Where on my body is the sensation coming from?• Posterior Parietal Cortex (note this is also part of visual “where” system too)

Damage to Posterior Parietal Cortex producesInability to process the location of a stimulus and its spatial relationship to other tactile stimuli

Plasticity of the Somatosensory System(1) The cortex is continuously being re-organized by experience

(2) The 1° somatosensory cortex is also re-organized following amputation of a body part (e.g., lower arm and hand)

• In such cases inputs to neighboring cortices invade the hand area • Thus, the brain can “hallucinate” the presence of a phantom limb every

time an area which invaded the phantom limb’s cortex is activated (e.g., touching face would now activate neurons in amputated hand area)

Notice that in the 1° somatosensory cortex, the distal arm/hand area is flanked by the upper arm area above and the face area below (both of which invade following amputation)

Recall that in 1° somatosensory cortex, the distal arm/hand area is flanked by the upper arm area above and the face area below (both of which invade following amputation)

Plasticity of the Somatosensory System

END – Lecture 15

PHYSIOLOGICAL PSYCHOLOGY (PSY 254)Lecture 16 (November 3, 2010)

THE SOMATOSENSORY SYSTEM II• Perception of pain• Neurochemistry of pain• Gate-control theory of pain• Cortical processing of pain

Pain Perception

Gate-Control Theory (Melzack & Wall, 1965)

1. C-fibers carry information to substantia gelatinosa (dorsal horn of spinal cord) 2. Substantia gelatinosa relays information to the brain stem 3. Brain stem relays information to the cerebral cortex (conscious experience) 4. Certain brain structures and A-fibers can stop pain messages by sending inhibitory signals to the substantia gelatinosa (thus “Closing the Gate” on pain):

(a) Periaqueductal gray or PAG (located in midbrain)(b) Periventricular gray or PVG (hypothalamic area, near 3rd ventricle)(c) A-fibers transmitting tactile information

Neurochemistry of Pain

Neurotransmitter that Transmits Pain Messages: Substance P

- neurotransmitter used by pain receptors- released by C-fibers that synapse onto substantia gelatinosa neurons- signals the presence of tissue damage and pain

Class of Neurotransmitters that Inhibit Pain Messages: Endorphins

- endogenous opiates (also called enkephalins)- neurons in PAG and PVG send axon terminals to substantia gelatinosa

• there they form axoaxonic synapses onto the C-fiber terminals • they release endorphins onto C-fiber terminals • block ascending pain by presynaptic inhibition

- also released by pituitary gland in response to stressful or painful situations- effects of endorphins can be blocked by opiate antagonists such as naloxone

Substantia Gelatinosa is Lamina II of the Dorsal Horn

**

Gate-Control Theory of Pain

Explains how a severely injured individual can ignore pain to, for example, rescue a loved one (higher brain centers activate neurons in PAG and PVG which “close the gate” on ascending pain).

Gate-Control Theory of Pain

Why A-fiber Stimulation Can Also Reduce Pain

Explains why rubbing an area produces relief.

Cortical Processing of Pain

3 Dimensions of Pain Perception:1. Sensory-discriminative

• detect pain and identify its source (can be wrong: e.g., referred pain)• processed initially in 2°(secondary) somatosensory cortex

2. Motivational-affective• emotional and motivational aspects - can it be endured• processed in anterior cingulate cortex (if anterior cingulate is damaged, pain is felt but not viewed as unpleasant)

3. Cognitive-evaluative• severity and how to deal with the pain• processed in prefrontal cortex

Allodynia may be experienced following tissue & nerve damage (abnormal enhanced pain response).

END – Lecture 16

PHYSIOLOGICAL PSYCHOLOGY (PSY 254)Lectures 17 & 18 (November 08 & 10, 2010)

COGNITIVE PROCESSES I & II

• The Frontal Lobe & Working Memory

• Memory Consolidation & Reconsolidation

• Long-Term Declarative Memory- episodic and semantic- patient H.M.- emotions and memory

• Long-Term Nondeclarative or Procedural Memory

• Amnesia and Alzheimer’s disease (medial temporal lobe)

• Effects of Prefrontal Cortex Damage

In Humans, the Frontal Lobe is the Largest Lobe

The Frontal Lobe and Cognition

• Frontal lobe is the largest brain structure occupies ~1/3 of the human brain

• Divided into 3 functional zones or areas1. prefrontal cortex (most anterior region – cognition, planning, etc…)

2. premotor cortex (anterior to motor cortex - movement)

3. primary motor cortex (or precentral gyrus - movement)

Relative size of the Prefrontal Cortex in different animals

Prefrontal Cortex is important for Working Memory

Working Memory (Baddeley & Hitch, 1974) • Coordinated, temporary storage of information in various sites in the cerebral cortex. • WM allows you to perform calculations in your head, to read, and solve problems.

• Intelligence may be linked to working memory capacity.

1. Working Memory for Object Identification - • can hold an object or series of objects in mind• thus can put a series of objects in order

(e.g., also face recognition)• IT cortex (visual object recognition) and PFC (storage centers)

2. Working Memory for Spatial Location - • holding in memory the spatial location of several objects at the same time

(e.g., playing chess)• right hemispheric regions are involved:posterior parietal, hippocampus, PFC

3. Working Memory for Verbal Information - • holding words in mind (e.g., reading or listening to someone speaking)• Broca’s and Wernicke’s areas (speech centers in the left hemisphere)• anterior cingulate cortex (in medial PFC)• left premotor cortex (rehearsing verbal material sub-vocally)

Brain Regions involved in Working Memory (WM)(depends upon the kind of information being held in WM)

Overview of Circuits Involved in Speech Production

Speech Paul Broca (1861) and Carl Wernicke (1874)

*

Anterior Cingulate Cortex (in medial PFC) • activated when working memory is used • coordinates working memory?

PET scans illustrating activation of brain regions during working memory for verbal information (e.g., think of uses for nouns or some other verbal task)

Note: PET scan measures changes in blood flow (increased blood flow is correlated with increased activity)

Memory and Consolidation of Memories

Short- and Long-term memory (William James, 1890)

• a limited memory system (e.g., can hold ~7 pieces of information)• holds information effortlessly for ~30 seconds before decaying • can hold information longer with rehearsal • postulated by Donald Hebb (1949) to result from reverberating circuits in the frontal lobes- Chunking information will allow compartmentalization and thus more retained

Short-term memory (i.e., working memory)

• postulated by Hebb to describe the shift of a memory from a relatively labileshort- term to a relatively stable long-term form (which can be made labile again by retrieval of the memory – reconsolidation)

Consolidation (& Reconsolidation)

• a memory system capable of storing large amounts of information for longperiods of time (e.g., years to decades)

• Hebb proposed that long-term memory results from structural changes to memory circuits

• there are two main long-term memory systems (declarative & nondeclarative)

Long-term memory

A Simple Model of the Learning Process

A Schematic Description of the Experiment by Misanin, Miller, and Lewis (1968)

Declarative Memory

• Also called explicit memory

• Involves conscious retention of facts and events

• Requires the hippocampus for initial storage

- patients with hippocampal damage exhibit amnesia

- retrograde amnesia (backward - old)cannot remember events just prior to injury

- anterograde amnesia (forward- new) cannot create new declarative memoriese.g., patient H.M. cannot form new memories

• Over time, the hippocampus is no longer required for declarative memory retrieval- thus, hippocampus serves a temporary, time-limited role

Schematic Definition of Retrograde Amnesia & Anterograde Amnesia

• 1953 - bilateral removal of medial temporal lobe structures to ameliorate epilepsy(e.g., hippocampus, entorhinal cortex, perirhinal cortex, amygdala)

• H.M. could not form new conscious memories since the surgery(e.g., impaired declarative memory)

Note: MRI involves placing a persons head in a strong magnetic field to detect radio waves emitted by hydrogen atoms throughout brain tissue

MRI of patient H.M.’s Brain (left image)

2 Forms of Declarative Memory

1. Episodic Memory• memory for events or episodes in one’s own life

(e.g., what one did yesterday or a meeting you had recently)• such memories are organized in time and identified by a particular context• includes not just verbal memory but also the perceptions

(e.g., can visualize the surroundings while recalling the information)Organized in time and space.

2. Semantic Memory• general knowledge or learned facts

(e.g., knowing the multiplication tables, history, geography, etc…)• does not include information about the context in which facts were learned

Effects of Emotional Arousal on Consolidation of Long-Term Memory

1. Memory is greater for emotionally charged events• easier to remember where you were on 9/11/2001 than other 9/11s• easier to remember your first date

2. When aroused, your body releases hormones (e.g., epinephrine)•Epinephrine activates the amygdala which enhances consolidation of memory• drugs that block effects of epinephrine interfere with memory formation

Nondeclarative Memory

• Also called implicit or procedural memory

• Involves nonconscious memory for learned behaviors

• Does NOT require the hippocampus

- instead, involves cerebellum and corticostriatal system

• One example of nondeclarative memory is the Priming Effect- improved ability to recognize particular stimuli after experience with them- e.g., word-stem completion task (rehearsal not permitted)

garden gar- (person would complete garden faster)window tar-tennis sin-

- priming involves posterior parietal and occipital cortex for the visual information and Broca’s area for conceptual information

• neurodegenerative disease characterized by severe memory loss

• Diagnosed by presence of plaques (Amyloid protein deposits) and tangles (tau protein filaments) which first form in temporal lobes and spread throughout forebrain

• initially, the disease destroys synapses and then eventually kills the neurons in the later stages of AD

• most common form of senile dementia in the elderly• anterograde amnesia for episodic and semantic memories• also retrograde amnesia• ACh levels (& other transmitters) are severely depleted in AD brains• current therapies involve acetylcholinesterase inhibitors (don’t work very well)• potential future therapies may involve immunization against Amyloid

Alzheimer’s disease

AD brain Control brain

Senile plaques in hippocampus

Senile Plaques and Neurofibrillary Tangles


AD brain Control brain



AD neuronsControl neuron

Reconstruction of Phineas Gage’s Brain

1848 - explosion sent iron rod through his cheek and up out the top of his head(destroyed mPFC)

Phineas Gage was a railroad foreman• before accident - very polite• after accident - disinhibited (displayed many of the symptoms of PFC damage)

Disorders Associated with Prefrontal Cortex Damage

1. Dysexecutive Syndrome• inability to coordinate complex behaviors with respect to goals and

task specific constraints(e.g., might stir coffee cup first and then add cream to the coffee)

2. Disinhibition• lack of behavioral control• impulsive, quick to anger, prone to rude childish remarks

(e.g., demonstrates utilization behavior - when left alone patient will inappropriately pick up a comb from a desk and use it)

• can also be tested using the Stroop Test or Wisconsin Card Sorting Test (PFC patients perseverate - i.e., unable to alter initial response)

3. Emotional Impairments• indifferent and apathetic to their own situation and to the needs of others

(e.g., people with PFC damage might laugh if they see someone crying)• irritable and prone to angry outbursts

4. Difficulty Planning• unable to organize behavior to plan several steps in advance• assessed by Tower of Hanoi Test or Multiple Errands Task

The Stroop Test for damage to prefrontal cortex

Patients with damage to prefrontal cortex do fine reading the words, naming the colors, but have great difficulty naming the color of the word when they are different

Tower of Hanoi Test of PFC function

Patients with damage to prefrontal cortex have great difficulty planning ahead to solve the Tower of Hanoi test

The Wisconsin Card Sorting Task

Patients with damage to prefrontal cortex do well initially but they perseverate on the initial rule and are unable to change (e.g., sort by number after initially being asked to sort by shape)

END – Lectures 17 & 18

COGNITIVE PROCESSES III1. Associative Learning

• Classical Conditioning• Trace vs. Delay Conditioning

2. Synaptic Plasticity

PHYSIOLOGICAL PSYCHOLOGY (PSY 254)Lecture 19 (November 29, 2010)

Classical or Pavlovian Conditioning

• Model system for studying associative learning (implicit & explicit)

• Allows for excellent experimental control over stimuli

• Studied in many species (e.g. human, monkey, rabbit, rat, mouse)

• Engages both cortical and subcortical brain regions

Ivan Pavlov1849-1936, physiologist

Classical (Pavlovian) Eyeblink Conditioning

• CS = conditional stimulus

(e.g., neutral stimulus such as an auditory tone)

• US = unconditional stimulus

(e.g., airpuff delivered to eye)

• UR = unconditional response

(e.g., eyeblink following airpuff)

• CR = conditional response

(e.g., eyeblink in response to the tone CS - prior to delivery of US)

• ISI = interstimulus interval

(e.g., time between onset of CS and onset of US)

• ITI = intertrial interval

(e.g., time between trials; from US offset to next CS onset)

Simple Neural Model of Classical Conditioning

Delay vs. Trace Eyeblink Conditioning

Delay Conditioning• CS and US are temporally contiguous (overlap in time)• requires fewer training trials• depends on brainstem and cerebellar circuitry• implicit learning

Trace Conditioning• CS and US are discontiguous (separated by stimulus-free trace interval)• requires many more training trials• still depends on brainstem and cerebellum to elicit a CR• but now also depends on higher brain structures (e.g., hippocampus) to learn• explicit learning (i.e., subjects that learn the task also express awareness whereas subjects that fail to learn do not express awareness)

Cellular Mechanisms of Learning and Memory

Synapses are plastic! • they can be added or removed• they can be strengthened or weakened• Synaptic Plasticity has two basic forms

long-term potentiation or LTP (strengthening)long-term depression or LTD (weakening)

LTP is a form of cellular memory!

Hebb’s Postulate (regarding conditions that cause a synapse to change)

“When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.”

- Donald Hebb, 1949

Modern interpretation? “Cells that fire together wire together!

Synaptic Plasticity

LTP was first discovered in the Hippocampus

Long-Term Potentiation

Strong Stimulus can be:• high frequency stimulation (e.g., 100 Hz)

Note: stimulation must be sufficient to produce enough postsynaptic depolarization to open NMDA receptors (see slide on induction of LTP, 3 slides from this one)

The Role of Summation in Long-Term Potentiation

LTP is input specific

Hebbian Plasticity

Can Think of the Weak Path as the CS and the Strong Path as the US (Classical Conditioning)

When 2 Different Pathways are Stimulated (e.g., One Weak and One Strong)• Weak-alone does nothing• Strong-alone strengthens strong pathway only• Weak + Strong together strengthens both pathways

Associative Long-Term Potentiation

Action potential primes NMDA receptors so that weak synapses active at the same time will become strengthened

Induction of LTP Requires Strong Postsynaptic Depolarization

The postsynaptic Ca2+ influx during depolarization is a critical trigger for induction of LTP

• Under normal conditions, synaptic stimulation activates only AMPA receptors (and thus a small synaptic response or EPSP occurs)

• Strong depolarization leads to activation of NMDA receptors, which let Ca2+ into the cell

• Ca2+ influx activates 2nd messengers, which leads to insertion of more AMPA receptors (and thus a larger synaptic response or larger EPSP)

Long-term potentiation (LTP)

Expression of LTP and LTD

1. Silent Synapses result from an absence of postsynaptic AMPA receptors

2. Synapses that were previously silent can become active following LTP (due to LTP causing insertion of AMPA receptors)

Final Note:• insertion of AMPA receptors = LTP (strengthening of synapse strength)

• removal of AMPA receptors = LTD (weakening of synapse strength)

END – Lecture 19(End of Material on Final Exam)

all

Education

course syllabus

final exam willfailthe

final grade

final exam score

extra credit makeup

course iscarlson

curving of exams

scheduled exams