functions of the nervous...

Functions of the nervous system

Nervous system consists of • Nerve cells: neuron• Neuroglia: glia

– Microglia: scavenger cells– Oligodentrogliocyte: myelin– Astrocyte: blood-bain barrier

• Fibrous: white matter• Protoplasmic: gray

Morphology of nerve cells

1. Cell body2. Dentrites: 5-73. Axon: 1

– Axon hillock

Function of the dendrites

• Traditional: extensions of the soma

• Recent observation:– Propagable AP formation– Dendritic spines increase

and disappear– Protein synthesis

Nerve fiber types and function

• Erlanger and Gasser: A, B, C

Nerve fiber types and function

• Lloyd and Hunt: I, II, III, IV

Axoplasmic transport

Axoplasmic flow:Anterograde transport (轴浆运输)

Fast transport: granule, vesicle mitochondria (400 mm/d)Slow transport: dissoluble substances (0.5-10 mm/d)

Retrograde transport (逆向运输): material taken up at the ending: (poliomyelitis)

Axoplasmic transport protein

• Fast anterograde transport is mediated by kinesin (驱动蛋白)

• Retrograde transport is mediated by dynein

Trophic effect of nerve

• By release trophic factors• Regulating the metabolism, protein

synthesis• Trophic factors are transported by

axoplasmic flow

Neurotrophins

• Definition: a number of proteins necessary for survival and growth of neurons

• Produced by: – Muscles– Neuronal innervated tissues– Neurons

Identified neurotrophins• Nerve growth factor (NGF)• Brain-derived neurothopic factor (BDNF)• Neurotropin 3,4,5 (NT-3,4,5)• Others:

– Glial cell line-derived neurotropic factor (GDNF)– Ciliary neurotropic factor (CNTF)– Leukemia inhibitory factor– Insulin-like growth factor I– Transforming growth factor– Fibroblast growth factor– Platelet-derived growth factor

Synaptic transmission in CNS

• Synapse• Presynaptic cell• Postsynaptic cell

Types of synapses in CNS• Chemical synapse

– Axosomatic– Axodendritic– Axo-axonal

• Electrical synapse: gap junction

Structure of Chemical Synapse

• Synaptic knob (terminal button)

• Vesicles • Neurotransmitter• Synaptic cleft• Presynaptic membrane• Postsynaptic membrane• Receptors

A

B

Synaptic vesicles

• Small, clear: – ACh, glycine, GABA, glutamate

• Small with a dense core:– Catecholamines

• Large with a dense core:– Neuropeptides

Chemical Synaptic transmission processes

AP reaches Depolarization at presynaptic membrane Ca2+ release Fusion of vesicle and presynaptic membrane Transmitter release Binding to receptor Electrical event on postsynaptic membrane

A

B

Electrical events in postsynaptic neurons

• Excitatory Postsynaptic Potentials (EPSP)• Inhibitory postsynaptic potential (IPSP)

Electrical events in postsynaptic neurons

1. Excitatory Postsynaptic Potentials (EPSP)– Depolarization potential– Begins about 0.5 ms– Peaks at 1-1.5 ms– Excitability ↑– Opens Na+ or Ca2+ ion channels

EPSP

Electrical events in postsynaptic neurons1. Excitatory Postsynaptic Potentials (EPSP)2. Inhibitory postsynaptic potentials (IPSP)

– Hyperpolarization potential– Begins about 0.5 ms– Peaks at 1-1.5 ms

– Excitability ↓– Opens Cl- ion channels

IPSP

Slow Postsynaptic Potentials

• Recorded at: autonomic ganglia, cardiac & smooth muscle, and cortical neurons

• Transmitters: peptides• Latency: 1-5 s, Last: 10-30 min• Slow EPSPs: decreases in K+ conductance• Slow IPSPs: increases in K+ conductance

Generation of the AP in the Postsynaptic Neuron

• A single input does not evoke AP

• Interplay of excitatory and inhibitory activity

• Initial segment: axon, axon hillock

• Propagated in two directions

• Wiping the slate clean

Inhibition at post synaptic neuron IN CNS

• Postsynaptic inhibition• Presynaptic inhibition

Postsynaptic Inhibition

• Inhibitory interneuron• Inhibitory transmitter• IPSP• Types:

– Reciprocal inhibition– Recurrent inhibition

Presynaptic Inhibition

• Axoaxonal synapse• Transmitter: GABA• Mechanism:

AP in neuron C→GABA release→ Cl- conductance↑→ AP↓→ Ca2+ influx ↓→ Transmitter release ↓→ EPSP↓

A

B

C

Presynaptic Facilitation

• Axoaxonal synapse• Mechanism:

serotonin →cAMP↑ →phosphorylation and close of K+ channels→prolonged AP →prolonged opening of Ca2+ ↑ → Ca2+ influx ↑→transmitter release ↑→EPSP ↑

A

B

C

Summation & Occlusion• Divergence: a neuron

discharges on many neurons

• Convergence: a neuron receives input of many neurons

• Summation:– Spatial – Temporal

• Occlusion:

Synaptic Delay

• 0.5 ms delay

• Determine reflex pathway is monosynaptic or polysynaptic

Characteristics of excitation in CNS

• One-way conduction• Central delay • Summation and occlusion• Excitatory rhythm changes• After discharge• Susceptible to changes of internal

environment• Easier to get fatigue

Chemistry of Transmitters• Chemical transmission: major role in excitatory

transmission• Nerve ending: biological transducer:

Electrical→Chemical →Electrical• Transmitter:

1. Synthetic enzyme system in presynaptic neuron2. Stored in vesicles and released 3. Receptors at postsynaptic membrane4. Inactive mechanism5. Agonist or antagonist

PRINCIPAL NEUROTRANSMITTERSYSTEMS

• Acetylcholine• Norepinephrine & Epinephrine• Serotonin• Histamine• Amino Acids:

– Excitatory Amino Acids: Glutamate & Aspartate– Inhibitory Amino Acids: Gamma-Aminobutyrate

• Opioid Peptides and Other Polypeptides• Gases: NO, CO, H2S

Acetylcholine

Acetylcholine Receptors

• Muscarine receptor (M receptor): end-plate, brain

• Nicotinic cholinergic receptor (N receptor): autonomic ganglia

Receptors for neurotransmitters

• Each ligand has many subtypes of receptors

• Several large families based on structure and function

• Presynaptic & postsynaptic recptors

• Concentrated in postsynaptic area• Prolonged exposure to their ligands

causes unresponsiveness

Reuptake• Back into • Two families of transporter proteins

– 12 transmembrane and cotransports the transmitter with Na+ and Cl–: NE, dopamine, serotonin, GABA, and glycine

– Made up of at least three transporters: glutamate into neurons and astrocytes

• Vesicular monoamine transporters (VMAT1, VMAT2): neurotransmitters from the cytoplasm to synaptic vesicles (reserpine)

Cotransmitters

• Traditional concept: a neuron has only one neurotransmitter (Dale principle)

• Neurotransmitter coexistence:– Catecholamine or serotonin + peptide(Norepinephrine + neuropeptide Y)

Neuromodulation and neuromodulators

• Chemicals synthesized and released by neurons

• Not participate in signal transfer

• Regulating the efficiency of synaptic transmission

• Neuropeptides or steroids

Reflexes

• Reflex: Response to stimulus with the participate of CNS

• Basic unit: reflex arc, 5 parts

Monosynaptic and polysynaptic reflexes

• Stretch reflex

‹#›

Section ⅩFunction of the Nervous

System

By: Ming-Jie Wang

E-Mail: [email protected]

Schedule

§ Today------Central Regulation of Visceral

Function; Neural Basis of Instinctual

Behavior & Emotions

§ Next Friday------Electrical Activity of the

Brain, Sleep and wakefulness; Higher

Functions of the Nervous system

About this lesson

§ Central Regulation of Visceral Function

l The autonomic nervous system

l Brain stem control of Visceral Functions

l Hypothalamus control of Visceral Functions

§ Neural Basis of Instinctual Behavior &

Emotions

l The limbic system and its function

l Emotions

l Motivation & Addiction

l Brain chemistry & Behavior

Chapter 44

Central Regulation of Visceral Function

§ Autonomic Nervous Systeml Sympathetic Division-norepinephrine

l Parasympathetic Division-acetylcholine

§ Brain stem (Medular Oblongata) control of

Visceral Functionl vital centers

§ Hypothalamus control of Visceral Function

l Feeding & Satiety (food intake)

l Water intake

l Body temperature regulation

l Relation to the pituitary gland

l Relation to cyclic phenomena

AUTONOMIC NERVOUS

SYSTEM (ANS)

‹#›

Introduction

The portion of the body nervous system that

controls the visceral functions is called the

autonomic nervous system (ANS). Impulses

initiated in the visceral receptors are relayed

via afferent autonomic pathways to the

central nervous system, integrated within it at

various levels, and transmitted via efferent

pathways to visceral effectors.

Outputs from the central nervous system

§ Somatic nervous system

l Innervate striated skeletal muscles

§ Autonomic nervous system

l Visceral /Vegetative nervous system

l Innervate smooth muscles, cardiac muscles, glands

and secretary epithelia

l Output is diffused

Autonomic Nervous System (ANS)

§ Self-governing

l Functioning independently of the will

(coordinates cardiovascular, respiratory, digestive,

excretory and reproductive systems)

§ Three divisions

l Sympathetic

l Parasympathetic

l Enteric

§ Efferent and afferent neurons

§ Pre- and post-ganglionic neurons

Sympathetic Division

(fiber)

3

Parasympathetic Division

Preganglionic cell bodies in

nuclei of brainstem or

lateral parts of spinal cord

gray matter from S2-S4

l Preganglionic axons

from brainstem pass to

effector through cranial

nerves

l Preganglionic axons

from spinal cord pass

through pelvic nerves to

effector

The postganglionic fiber is short

§ Dual innervation: Both divisions innervate a particular

organ

l Generally have opposite effects

l In some organs only sympathetic innervation

( blood vessels, kidney, sweat glands )

§ Tonic activity

Originate in the tonic activity of the autonomic centers

§ Actions are affected by the physiological status of the

organ

§ Physiological significance

l Sympathetic: prepares the body to meet an

emergency situation

l Parasympathetic: protection, energy reservation

(digestion and absorption)

‹#›

Sympathetic and

parasympathetic

nervous systems

Sympathetic

preganglionic fiber is

usually short, while

parasympathetic

preganglionic fiber is

usually long.

Chemical transmission at autonomic junctions

§ All preganglionic neurons (both divisions) are

cholinergic, they release ACh and stimulate N2 nicotinic

receptors

§ All postganglionic parasympathetic neurons are

cholinergic, they release ACh and stimulate M receptors

on viscera

§ Most postganglionic sympathetic neurons are

noradrenergic, they release norepinephrine onto visceral

targets.l Except: Sympathetics innervating sweat glands and blood

vessels in skeletal muscle (sympathetic vasodilator nerves) are

cholinergic

§ Cotransmitters can be released: ATP, NO, peptide…

ACh AChSweatglands

Striatedmuscle

ACh

SOMATIC NERVOUS SYSTEM

HeartSm. mus.Glands

ACh AChParasympathetic

AChE, NE

Ad. M.

HeartSm. mus.Glands

ACh NE

AUTONOMIC NERVOUS SYSTEM

Sympathetic

Location of ANS Receptors

Somatic and Autonomic Nervous System

Somatic1. Skeletal muscle

2. Conscious and

unconscious movement

3. Skeletal muscle contracts

4. One synapse

5. Acetylcholine

Autonomic1. Smooth and cardiac

muscle and glands

2. Unconscious regulation

3. Target tissues stimulated or inhibited

4. Two synapses

5. Acetycholine by preganglionic neurons and ACh or norepinephrine by postganglionic neurons

Functions of Sympathetic and

Parasympathetic Nervous System

(1)Sympathetic and parasympathetic Nerves

innervate the same organ.

(2) Sympathetic and parasympathetic "tone"

The sympathetic and parasympathetic systems are

continually active, and the basal rates of activity are

known, respectively, as sympathetic tone or

parasympathetic tone.

(3)Effects of regulating visceral by Autonomic

(vegetative) Nervous System are concerned with the

condition of the organs.

‹#›

Responses of effector organs

to autonomic nerve impulses

Acetylcholine

§ Nicotinic receptors

l Nm (muscular-type or N2): skeletal muscle

l Nn (neuron-type, or N1): autonomic ganglia,

CNS

§ Muscarinic receptors

l Postganglionic parasympathetic and a few

sympathetic sites, CNS (also autonomic gang.)

l Receptor subtypes: M1-5

Catecholamines§ Norepinephrine

l Postganglionic sympathetic, CNS, adrenal medulla

l Receptors: a1, a2, b1

§ Epinephrine

l Adrenal medulla, CNS

l Receptors: a1, a2, b1 , b2

§ Dopamine

l Autonomic ganglia, CNS

l Receptors: D(1-5)

Function of ANS

on the target

organs

Effector Sympathetic Parasympathetic

Radialmuscle

Contraction(mydriasis, a1)

—

Sphinctor — Contraction(miosis)

Ciliarymuscle

Slight relaxa-tion (b2)

Contraction (nearvision)

Eye

Cornea

Lens

Ciliary

muscle

Iris

(M)

SA node

Atria

AV node

Ventricles

Heart


SA node Tachycardia(b1,b2)

Bradycardia

Atria contractilityand conduction(b1,b2)

contractility,conduction(usually)

AV node conductionand auto-maticity (b1,b2)

conduction

Ventricles contractility,conduction, andautomaticity(b1,b2,a1)

—

Heart


Skin andmucosa

Constriction(a1,a2)

Dilation (?)

Skeletalmuscle

Constriction(a), dilation(b2)

—

Salivaryglands

Constriction(a1,a2)

Dilation

Erectiletissue

Constriction(a)

Dilation

Blood vessels

‹#›


Bronchialsm. musc.

Relaxation (b2) Constriction

Bronchialglands

(a1),(b2),secretion

secretion

Salivaryglands

Viscous,amylasesecretion(a1,b1,b2)

Profuse waterysecretion

Lungs and salivary glands


Smoothmuscle

motility andtone(a1,a2,b1,b2)

motility andtone

Sphincters Contraction(a1)

Relaxation

Secretions secretion (a2) secretion

Liver Glycogenolysis,gluconeogene-sis (a1,b2)

Glycogensynthesis

Gastrointestinal tract and liver

Sympathetic nervous system

§ Sympathetic nervous system prototypically “fight” or

“flight”.

§ Associated with increased

l energy expenditure,

l cardiopulmonary adjustments for intense activity,

l blood flow adjustments for maximum energy expenditure.

§ Tonic noradrenergic discharge to the arterioles

maintains arterial pressure

SNS - Fight & Flight Reaction

You’re walking alone at night and all the sudden you hear

an unfamiliar noise near by… In a matter of seconds, l your heart rate increases dramatically,

l blood vessels in your skeletal muscles dilate,

l blood vessels in the visceral muscles constrict,

l blood vessels in the skin constrict (limits bleeding from

wounds),

l digestion is ceased,

l your liver ramps up glucose release (supplying more

energy),

l your pupils dilate (more light into the eyes),

l salivary production decreases,

l sweat increases.

Autonomic Nervous System

• Cholinergic

• Day-to-day living

• Relaxation, digestion

• Dominated by

Acetylcholine

• Anabolic

• Noradrenergic

• Emergency situations

(Fight & Flight)

• Dominated by

Norepinephrine

(Epinephrine)

• Catabolic

Interactions of the ANS

§ Most visceral organs are innervated by both types of nerves.

§ Most blood vessels are innervated only by sympathetic nerves.

§ PS activity dominates the heart and GI tract.

§ Activation of the sympathetic division causes wide spread, long-lasting mobilization of the fight-or-flight response.

§ PS effects are highly localized and short lived.

‹#›

BRAIN CONTROL OF

VISCERAL FUNCTIONS § Spinal cord is primary center of visceral

activity

§ There are some primary centers of visceral

activity in the spinal cord. Some simple

reflexes are integrated in the spinal cord.

l emptying of full bladder

l defecation

l diaphoresis

l blood vessels tonic contraction

Spinal cord

Medulla oblongata

§ The medullary centers for the autonomic

reflex control of the circulation, heart, and

lungs are vital centers because damage to

them is usually fatal.

§ Swallowing, coughing, sneezing, and

vomiting are also reflex responses

integrated in the medulla oblongata.

Midbrain

§ Center for the pupillary reflex to light and

accommodation

§ A higher center for regulation of visceral functions

— integration of higher cortical and limbic systems

with autonomic control (visceral, somatic, behavior,

emotion)l A prominent example: defense reaction

§ Connections with other brain areasl Limbic forebrain

l Brain stem nuclei

l Spinal cord

The hypothalamusFunctions of Hypothalamus

①Regulation of food intake

②Regulation of body water-balance

③Regulation of body temperature: heat-

sensitive-neurons and cold-sensitive neurons.

④Control of the pituitary gland

⑤Control of biorhythms

⑥Defensive reaction: fear, rage

⑦Other “instinct” behavior : such as sexual

behavior

‹#›

§ Food intake is regulated not only on a meal-to-

meal basis but also in a way that generally

maintains body weight at a given set point

§ Depends on the interaction of two areas:

l Feeding center: lateral hypothalamus

(Bilateral lesions cause anorexia)

l Satiety center: ventromedial hypothalamus

(Bilateral lesions cause overeating and become obese)

1. Role in food intakethalamus

mamillo-thalamic

tract

dorsalhypothalamic

area

dorsomedialnucleus dorsomedial

nucleus

Lesions in ventromedial nucleus

Lesions in lateral hypothalamus

Voracious appetite Loss of appetite

Effects of hypothalamic lesions on feeding

Feeding centerSatiety center

Short-term regulation of Feeding behavior

§ Satiety center functions by inhibiting the feeding

center.

§ The drive to eat is inhibited by satiety signals

which occur during eating and digestion:

l Gastric distension

l Cholecystokinin (CCK) and glucagon, somatostatin

l Insulin

l High glucose utilization (glucose-sensitive neurons

detecting the arteriovenous blood glucose difference)

Long-term regulation of Feeding behavior

§ Lipostatic hypothesis — a mechanism to maintain

energy homeostasis

§ The brain monitors the amount of body fat

§ Communication from adipose tissue to the brain

§ Leptin:

l released by adipocytes (encoded by ob gene)

l regulates body mass by acting on hypothalamus

l Leptin ↑: activate leptin receptors on neurons of arcuate

nucleus, anorectic peptides (αMSH and others) released

and inhibit feeding behavior

l Leptin ↓: stimulate another type of arcuate nucleus

neurons, orexigenic peptides (NPY and orexin) released

and stimulate feeding behavior

ob/ob mouseNormalmouse

Parabiosis

ob/ob mice

§ Lack both copies of ob gene

§ Lack plasma leptin

§ High motivation to eat

§ Obese

§ Treating with leptin completely

reverses obesity and feeding

behavior

§ Parabiosis: an ob/ob mouse is

surgically fused with a normal

mouse (sharing common blood

supply), its feeding behavior and

obesity are reduced

Increased food intake,

decreased energy

expenditure

FAT DEPOTS

Increased fat deposition

Increased leptinsynthesis

HYPOTHALAMUS

Increased activation

of leptin receptors

Increased plasma

leptin concentration

Feedback control of fat depots by leptin

+

+

+

‹#›

Body fluid homeostasis

§ Water intake — thirst, drinking

(vasopressin secretion, PVN, SON)

l Body fluid osmolality — brain osmoreceptors

(organum vasculosum of the laminar terminalis, OVLT)

l Extracellular fluid volume — renin-angiotensin

system involved

(angiotensin Ⅱ SFO thirst drinking)

§ Water excretion — renal collecting duct

2. Role in water intakeRegulation Of Water-Balance

Hypertonic Low volume

3. Role in body temperature regulation

Heat production heat loss

§ The center of regulating body temperature is

located in the hypothalamus.

l Decorticated animal — body temperature stable

l Brain transection below diencephalon

— body temperature unstable

§ Temperature-sensitive neurons in hypothalamus

— Preoptic anterior hypothalamus ( PO/AH )

(body temperature-regulating center)

§ Set point for body temperature control

Regulation of body temperature

4. Relation to the pituitary gland

Hypothalamohypophyseal

tract 下丘脑垂体束 (neural

connection)

Hypophyseal portal system

垂体门脉系统 (vascular

connection)

Control Of Anterior Pituitary Secretion

§ Anterior pituitary secretion is controlled by

chemical agents carried in the portal hypophyseal

vessels from the hypothalamus to the pituitary.

§ There are 6 established hypophysiotropic hormones

(促垂体激素). The releasing hormones can trigger

the anterior pituitary gland releasing, but the

inhibition hormones reduce their releasing.

‹#›

§ Biological rhythms: Many physiological

functions vary in a pattern that repeats itself

daily, monthly or annually.

§ These rhythms appear to be endogenous

because they persist even in the absence of

time cues

§ The hypothalamus is thought to play a major

role in regulating all of these biological

rhythms

5. Relation to cyclic phenomenaCircadian rhythms

§ Circadian rhythms: Most homeostatically

regulated functions exhibit peaks and valleys

of activity that recur approximately daily.

§ Body temperature, sleep-wake cycles and

some hormones release

Suprachiasmatic nucleus (SCN)

§ SCN, a center in the hypothalamus, drives the circadian

rhythms

§ Lesions of the nuclei disrupt circadian rhythm in the

secretion of ACTH and melatonin

§ The nuclei receive input from the eye (retinohypothalamic

fibers)

§ Synchronize various body rhythms to

light-dark cycle

Chapter 45

Neural Basis of Instinctual

Behavior & Emotions

§ The limbic system and its function

§ Emotions

§ Motivation & Addiction

§ Brain Chemistry & Behavior

‹#›

The limbic system

§ A rim of cortical tissue around the hilum of the cerebral

hemisphere and a group of associated deep structures: the

amygdala, hippocampus, and septal nuclei

§ Regulation of visceral functions, emotion, behavior

Instinctual behavior

§ Life-maintaining functions — from millions of

years of evolution

§ Survival of an individual — Eating, drinking

§ Survival of a species — Reproduction, sex-

related behaviors

§ Associated with emotional responses

§ Regulated by hypothalamus and limbic system

Emotions

§ Emotions have both mental and physical

components (involve cognition, affect, conation and

physical changes)

§ Feelings (love, hate, disgust, joy, shame, envy, guilt,

fear, anxiety, ……)

§ Neural basisl Cortex is involved in the experience of emotion

l Hypothalamus governs the behavioral expression

of emotion

l Hypothalamus and cortex link each other

Fear and rage

Klüver-Bucy syndrome — bilateral temporal lobectomy

in monkey has dramatic effect on the animal’s

responses to fearful situations

§ Emotional changes ( an apparent decrease in fear, let the

human stroke them and pick them up, both the normal

experience and expression are severely decreased)

§ Hypermetamorphosis ( irresistible compulsion to examine

things, run around and touch everything and place it in mouth)

§ Altered sexual behavior ( strikingly increased interest in sex)

§ Psychic blindness ( not seem to recognize common objects)

Defense reaction

Stimulation of the medial hypothalamus of a cat —§ Somatic and behavioral responses: growl, hiss, fold ears back,

arched back, hair erection, …… highly coordinated set of

behaviors normally occurs when feels threatened by an enemy

— fight-or-flight response

§ Visceral responses: increase in BP, HR, cardiac output,

pupillary dilatation, muscular vasodilation, splanchnic

vasoconstriction

§ Affective aggression (a threat attack): hiss, spit, arching back,

but would usually not attack the victim (a nearby rat)

§ Predatory aggression (a silent biting attack) by stimulating the

lateral hypothalamus: no dramatic threatening gestures, but

would move swiftly toward a rat and viciously bite its neck

Amazing cases in humans

§ Phineas Gage in 1848: Passage of an iron

rod through the head, Gage was no longer

Gage

§ Surgery to reduce human aggression:l Psychosurgery: early in 20th century

l Electric coagulation of amygdala

l Frontal lobotomy: in 1949 the Nobel Prize

in medicine was awarded to Dr. Egas oniz

for his development of the frontal

lobotomy technique (tens of thousands

were performed lobotomies following

World War Ⅱ, though not being performed

anymore now)

‹#›

Anxiety

§ Mediated by a2 GABAA receptor

§ Relieved by benzodiazepines

Motivation

§ Self-stimulation:

l “Pleasure areas” — septal area,

lateral hypothalamus, the medial

forebrain bundle, ……reward system

l “Displeasure areas” — medial

hypothalamus, lateral midbrain

punishment system

§ Brain stimulation in humans:

l Septal area, caudate nucleus, ……

Patients with intractable pain

§ D3 dopaminergic receptors Self-stimulation

Addiction

§ Associated with the reward system, particularly

with the nucleus accumbens (伏隔核)

§ Mesocortical dopaminergic neurons

§ Increase the amount of dopamine available to act

on D3 receptors in the nucleus accumbens

Brain Chemistry & Behavior

§ Aminergic systems (胺能系统) in the brain

l Serotonin, Norepinephrine, Epinephrine, dopamine

§ Histamine

§ Acetylcholine

l Alzheimer’s disease

§ Opioid peptides

Section ⅩFunction of the Nervous

System

By: Ming-Jie Wang

E-Mail: [email protected]

Responses of effector organs to

autonomic nerve impulses

§ Acetylcholine

l N1,2 , M1-5

§ Norepinephrine

l a1, a2, b1

§ Epinephrine

l a1, a2, b1 , b2

Function of ANS on the target organs

§ Eye

§ Heart

§ Blood vessels

§ Lungs and salivary glands

§ Gastrointestinal tract and liver

Medulla oblongata

§ The medullary centers for the autonomic

reflex control of the circulation, heart, and

lungs are vital centers because damage to

them is usually fatal.

§ Swallowing, coughing, sneezing, and

vomiting are also reflex responses

integrated in the medulla oblongata.

Functions of Hypothalamus

①Regulation of food intake

②Regulation of body water-balance

③Regulation of body temperature: heat-

sensitive-neurons and cold-sensitive

neurons.

④Control of the pituitary gland

⑤Control of biorhythms

⑥Defensive reaction: fear, rage

⑦Other ―instinct‖ behavior : such as sexual

behavior

Instinctual behavior

§ Life-maintaining functions — from millions

of years of evolution

§ Survival of an individual — Eating, drinking

§ Survival of a species — Reproduction, sex-

related behaviors

§ Associated with emotional responses

§ Regulated by hypothalamus and limbic

system

Addiction

§ Associated with the reward system, particularly

with the nucleus accumbens (伏隔核)

§ Mesocortical dopaminergic neurons

§ Increase the amount of dopamine available to

act on D3 receptors in the nucleus accumbens

Brain Chemistry & Behavior

§ Aminergic systems (胺能系统) in the brain

l Serotonin, Norepinephrine, Epinephrine,

dopamine

§ Histamine

§ Acetylcholine

l Alzheimer’s disease

§ Opioid peptides

About this lesson§ Electrical Activity of the Brain, Sleep and

wakefulnessl Electrical Activity of the Brain

• Evoked Cortical Potentials

• The Electroencephalogram

l The Reticular Activating System

l Sleep physiology

§ Higher Functions of the Nervous systeml Learning & Memory

• Forms of memory

• Habituation & Sensitization

• Conditioned Reflexes

• Neural Basis of learning and Memory

l Cerebral Dominance and language

Chapter 46

Electrical Activity of the Brain, Sleep and

wakefulness

§ Sleep and wakefulness: circadian

periodicity

§ Universal among higher vertebrates

§ Sleep is a readily reversible state of

reduced responsiveness to and interaction

with the environment. It is an active part of

the normal function of the body.

§ Compare to coma and general anesthesia

ELECTRICAL ACTIVITY OF

THE BRAIN

Electric activity of cerebral cortex

§ Spontaneous electric activity of the brain

l Electroencephalogram (EEG)

l Brain death: a maintained flat EEG

§ Evoked cortical potential

Evoked cortical potential

§ Definition: The electrical events that

occur in the cortex after stimulation of a

sense organ can be monitored.

§ Component:

l Primary response

l Secondary response

l After discharge

Evoked cortical potential

Animal experiment

§ Guinea pig is anesthetized to eliminate

background EEG

§ Stimulation of sciatic nerve

§ Recording electrode on the sensory cortex

§ A latency followed by a positive-negative

wave (primary response)

§ A larger, more prolonged positive deflection

(diffuse secondary response)

latency

primary response

secondary response

after discharge

Somatosensory evoked potential

§ Elicited by stimulation of the

peroneal nerve

§ Component:

Primary response

highly specific in its location

large pyramidal cells

Secondary response

diffuse

activity in projections from the

midline and related thalamic

nuclei

After discharge (cortex-thalamic circuit)

§ Can be used clinically to assess

the integrity of a sensory pathway

Electroencephalogram (EEG)

§ Definition: The record of the variations in potential

recorded from the brain is called the EEG.

§ EEG can be recorded with scalp electrodes through

the unopened skull or with electrodes on or in the

brain. The term electrocorticogram (EcoG) is

sometimes used to refer to the record obtained with

electrodes on the pial surface of the cortex.

§ Used clinically diagnose and localize brain lesions,

tumors, infarcts, infections, abscesses, epileptic

lesions and brain death.

spontaneous

cortical

electrical

potentials

Different waves in EEG

Alpha waves (alpha rhythm)

§ Adult human at rest, eye

closed, mind wandering,

most prominent wave of

EEG

§ Fairly regular

§ Most marked in the

parieto-occipital area

§ Frequency:8-12 cycles/sec

§ Amplitude: 50100 V

Alpha Block

§ α rhythm is replaced by fast, irregular low-voltage

activity when the eyes are open and attention is

focused on something (arithmetic solving) . This

phenomenon is called alpha block.

§ Known as ―arousal‖ or ―alerting response‖

Beta waves (Beta rhythm)

§ Appears during

cortical activity

§ Strongest from

frontal lobes

§ Frequency:18-30

cycles/sec

§ Amplitude: 520 V

Theta waves

§ Emitted from temporal

and occipital lobes

§ Common in newborn,

some in sleep adult

(drowsy states)

§ Adult indicates

emotional stress

§ Frequency:4-7

cycles/sec


Delta waves

§ Large, slow waves

§ Common during deep

sleep and awake

infant

§ In awake adult

indicate very serious

brain damage

§ Frequency:0.5-4

cycles/sec


Physiological basis of EEG

§ Synchronized activity: neural components

discharge rhythmically

§ Electrical activities of the dendrites of cortical

cells correlate with postsynaptic potential

§ Reverberating activity between cortex and

nonspecific thalamic nuclei

§ EEG arousal: by stimulating the midbrain

ascending reticular activating system (ARAS)

[Lesion of midbrain tegmentum: synchronization,

comatose for long periods]

§ Currents in extracellular space generated by

summation of EPSPs and IPSPs

§ Continuous graph of changing voltage fields at scalp

surface resulting from ongoing synaptic activity in

underlying cortex

§ Inputs from subcortical structures (Thalamus)

EEG Records During

Epileptic Seizure

Epilepsy is characterized by

uncontrolled excessive activity of

either a part or all of the central

nervous system.

Grand mal epilepsy:

characterized by extreme

neuronal discharges in all areas

of the brain, last from a few

seconds to 3 to 4 minutes.

Petit mal epilepsy: Characterized

by 3 to 30 seconds of

unconsciousness or diminished

consciousness during which the

person has several twitch-like

contractions of the muscle.

THE RETICULAR ACTIVATING

SYSTEM

Wakefulness and Sleep

Maintenance of wakefulness§ Stimulation of the ascending reticular activating

system (ARAS): stimulation of the midbrain reticular

formation (RF) causes activation of the cortex and

awakes a sleeping animal

§ Transmitter involvedl acetylcholine (phasic action)

l noradrenergic system (tonic action, Locus ceruleus, 蓝斑)

§ EEG arousalcholinergic system (RF)

§ Behavioral arousaldopamine system (substantia nigra)

黑质

RAS is cut off

SLEEP PHYSIOLOGY

Sleep

§ Sleep is a behavior and an altered state of

consciousness

l Sleep is associated with an urge to lie down for several

hours in a quiet environment

• Few movement occur during sleep (eye movements)

l The nature of consciousness is changed during sleep

• We experience some dreaming during sleep

• We may recall very little of the mental activity that occurred

during sleep

§ We spend about a third of our lives in sleep

l A basic issue is to understand the function of sleep

Importance of Sleep

§ Sleep is necessary for survival

§ Sleep appears necessary for our nervous systems to work properly.

§ During the SWS, growth hormone secretion increase and important for the infants growth and physical restorative process of adult

§ During REM, brain blood flow and protein synthesis increase, and it is important for the mental development of infants and long-term memory and mental restoration in adults.

§ Daily sleep requirements decline with age

What Happens if We are Deprived of Sleep?

§ Lack of alertness

§ Fatigue

§ Memory problems

§ Irritability

§ Depression

§ Lack of motivation

§ Accidents

§ Fibromyalgia

Two types of sleep

§ Slow wave sleep (SWS)/non-REM sleep (NREM):

A person falling asleep first enters this stage, and

passes through four stages of NREM during the

first 30-45 minutes of sleep.

§ Fast wave sleep (FWS) / Rapid eye movement

(REM) sleep: Occurs after the fourth NREM stage

has been achieved. Back-and-forth movements of

the eyes under closed lids, accompanied by

autonomic excitation.

l Dreams occur

l EEG activity is rapid (paradoxical sleep)

Slow wave sleep§ EEG changes as one falls asleep

l Wakefulness: random pattern of fast waves of low voltage

l Quiet restfulness: one closes eyes — α rhythm, sleep

spindles

l Light sleep: replaced by larger and slower waves — θ

rhythm

l Deep slow wave sleep: high voltage δ rhythm

l Thus, EEG waves are slow and synchronized

§ Characteristicl decreased heart rate and blood pressure

l slow and regular breathing

l reduced sensory functions

l reduced muscular tone and reflex activity

l increased growth hormone release

Four stages of SWS

Stage 1eyes are closed and relaxation begins; the EEG shows alpha waves; one can be easily aroused

Stage 2EEG pattern is irregular with sleep spindles (high-voltage wave bursts); arousal is more difficult

EOG

EOG

EMG

CENTRAL

FRONTAL

OCCIP

EOG

EOG

EMG

CENTRAL

FRONTAL

OCCIP

Stage 3

sleep deepens; theta and delta waves appear; vital signs decline; dreaming is common

Stage 4

EEG pattern is dominated by delta waves; skeletal muscles are relaxed; arousal is difficult

EOG

EOG

EMG

CENTRAL

FRONTAL

OCCIP

EOG

EOG

EMG

CENTRAL

FRONTAL

OCCIP

Genesis of slow-wave sleep

§ Stimulation (low frequency of 8/s) of the following

brain areas produces slow-wave sleep

l Diencephalic sleep zone: posterior hypothalamus

l Medullary synchronizing zone: RF at the level of NTS

l Basal forebrain sleep zone: preoptic area, diagonal band

§ Neurotransmitters involved

l SWS: 5-HT (serotonin antagonist increases SWS in

human)

l REM: 5-HT, norepinephrine, Ach

l PGD2 in medial preoptic area increases SWS and REM

§ Humoral factors: Sleep peptide (?)

Chemical Control of Sleep/Waking

§ Sleep is regulated: loss of SWS or REM sleep is made up somewhat on following nightsl Does the body produce a sleep-promoting chemical

during wakefulness or a wakefulness-promoting chemical during sleep?

§ Unlikely that sleep is controlled by circulating chemicals:l Siamese twins share the same circulatory system, but

sleep independently

l Bottle-nose dolphins: the two hemispheres sleep independently

Fast wave sleep/REM Sleep§ Desynchronized EEG pattern ( resembles

wakefulness — beta rhythm)

§ Characteristic

l The autonomic nervous system is in a state of excitation

• Heart-rate quickens, blood pressure increases

• Breathing more irregular and rapid

l further decrease in muscular tone and reflex activity

l Recallable, vivid, emotional dreams

l Physiological arousal threshold increases

§ Mechanism: Pontogeniculo-occipital (PGO) spikes

§ May be involved in memory consolidation.

Important for reinforcing memory traces

REM Dreaming NREM Dreaming

§ ―vivid and exciting‖

§ 3~4 per night

§ Longer, more

detailed

§ Fantasy world

§ ―just thinking‖

§ Shorter, less

active

§ Midst of nowhere

§ Logical, realistic

Normal sleep cycles§ Slow-wave sleep occurs first, passes through

stages 1, 2, 3 and 4 (spends 80～120 min)

§ Sleep then lightens, and a REM sleep follows

(20 ～30 min)

§ This cycle is repeated throughout the night

l 4～6 cycles per night

l Cycles are similar, but less stages 3 and 4, and more

REM sleep towards morning

§ Can be awakened from both slow-wave and

REM sleep

§ The suprachiasmatic and preoptic nuclei of the

hypothalamus regulate the sleep cycle

Children

Young adults

Elderly

awakeREM

1234

awakeREM

1234

awakeREM

1234

1 2 3 4 5 6 7

1 2 3 4 5 6 7

1 2 3 4 5 6 7

Sle

ep st

ag

es

Sle

ep st

ag

es

Sle

ep st

ag

es

Normal sleep cycles at various ages

Percent of total sleep time in

stage 4 sleep

Percent of total sleep time in

REM sleep

Total sleep time

Per

cen

tP

erc

en

tH

r/d

ay

Insomnia:

Sleeping pills (benzodiazepines)

Narcolepsy:

Sleep disorders

§ Frightening dream episodes

§ Occur in the REM stages

§ Last about 20 minutes

§ Can be result of taking drugs that affect neurotransmitter action or from drug withdrawal

§ Severe cases can be treated with medication

Diazepam (tranquilizer)

Nightmares

Tips for Getting a Good Night’s Sleep

§ Avoid caffeine and alcohol after dinner

§ Keep a routine

§ Don’t nap during the day

§ Don’t go to bed hungry or right after

eating

§ Exercise

§ Stop smoking

Chapter 47

Higher Functions of the Nervous

system

LEARNING & MEMORY

Learning & Memory

§ Learning is a process of nervous system

activity to alter behavior and adapt to

environment on the basis of experience .

§ Memory is the ability to the storage of

information and recall past events at the

conscious or unconscious level.

Forms of memory

Declarative (Explicit) or Nondeclarative (Implicit) Memory

§ Declarative (Explicit) -- conscious recall of

events

l Episodic - knowledge of your own past

experiences (events)

l Semantic - general knowledge of the world (words,

rules, language)

§ Nondeclarative (Implicit) -- often totally

unconscious

l learned skills or habitual responses

l Nonassociative (habituation, sensitization)

l Associative (conditioning)

Forms of memory

Declarative (Fact) memory

§ Entails learning explicit information

§ Is related to our conscious thoughts and our language ability

§ Is stored with the context in which it was learned

Nondeclarative (Skill) Memory

§ Skill memory is less conscious than fact

memory and involves motor activity

§ It is acquired through practice

§ Skill memories do not retain the context in

which they were learned

Memory

§ The three principles of memory are:

l Storage – occurs in stages and is continually changing

l Processing –accomplished by the hippocampus and surrounding structures

l Memory traces – chemical or structural changes that encode memory

§ Short-term memory

l Lasts seconds to hours

l it is the memory of a few facts, words, numbers,

letters.

l Memory traces are subject to disruption

l working memory: temporary storage for

seconds, current information

§ Long-term memory

l tertiary memory and secondary memory

l Stores memories for hours, days, months,

years and sometimes for life.

l Memory traces are resistant to disruption

Transfer from STM to LTM

§ Factors that affect transfer of memory from

STM to LTM include:

l Emotional state – we learn best when we are

alert, motivated, and aroused

l Rehearsal – repeating or rehearsing material

enhances memory

l Association – associating new information with

old memories in LTM enhances memory

Simple passage of time after learning has minimal effect on retention

Forgetting as a result of decay?

Forgetting as a result of interference

§ Retroactive Interference

Current learning interferes with recall of

previously learned material

§ Proactive Interference

Prior learning interferes with retention of

new information

Retrograde and Anterograde Amnesia

Time

Retrograde Anterograde

Head Trauma

Forms of learning

§ Nonassociative learning

l Habituation

l Sensitization

§ Associative learning

l Classic conditioning

l Operant conditioning

Nonassociative learning

No paired stimulus/response

§ Habituation - becomes less responsive to

repeated no-harmful stimulus

§ Sensitization - becomes more responsive

to repeated harmful stimulus

Associative learning

Paired stimulus/response

§ classical conditioning (two stimuli are paired,

e.g. when the light shines ----- get food)

§ operant conditioning (stimuli and response

are paired, e.g.push lever = food)

Classic conditioning

§ It is a classical example of associative

learning.

§ Pavlov’s classic experiment

l Unconditioned stimulus (US)

l Conditioned stimulus (CS)

Operant conditioning

(trial-and-error learning)

§ A predictive relationship between response and a

stimulus (must have predictive element)

§ behaviors that are rewarded tend to be repeated;

those that cause aversive consequences are not

repeated

§ timing is important

§ Typical experiment: Animal is taught to perform a

task (pressing a bar) in order to obtain a reward

Conditioned Reflex

§ Definition: A conditioned reflex is reflex

response to a stimulus that previously elicited

little or no response (CS), acquired by

repeatedly pairing the stimulus with another

stimulus that normally does produce the

response (US).

§ Internal inhibition (Extinction) & External

inhibition

§ Form of conditioned reflex

（1）Classical conditioning reflex

（2）Operant conditioned reflex

Elementary Principle of Conditioned Reflex

§ Reinforcement: When unconditioned and

conditioned stimuli are applied in the correct

temporal sequence for a sufficient number of

times, ultimately presentation of the conditioned

stimulus alone will evoke the response that

originally could elicited only by the unconditioned

stimulus.

§ Extinction: If the conditioned stimulation is

presented repeatedly without the unconditioned

stimulation, the conditioned reflex eventually dies

out.

Mechanism of memory§ Morphology

l Association areas of cortex, hippocampus, thalamus

l New synaptic connections established

§ Neurophysiology

l Duration of neuronal activities

l Neuronal circuits (Papez circuit)

l Synaptic activity (habituation, long-term potentiation)

§ Biochemistry

l Protein synthesis

l Neurotransmitters (ACh, catecholamine,

vasopressin)

Structures Involved in Declarative Memory

§ Declarative memory involves the following

brain areas:

l Hippocampus and the amygdala

l Specific areas of

the thalamus and

hypothalamus

l Ventromedial

prefrontal cortex

and the basal

forebrain

Major Structures Involved with Skill Memory

§ Skills memory involves:

l Corpus striatum – mediates the automatic connections between a stimulus and a motor response

l Portion of the brain receiving the stimulus (visual in this figure)

l Premotor and motor cortex

Synaptic plasticity

§ Habituation

§ sensitization

§ Long-term potentiation (discovered in year 1973)

Sensitization

§ A repeated stimulus produces a greater

response if it is coupled one or more

times with an unpleasant or a pleasant

stimulus, e.g. the mother who sleeps

through many kinds of noise but wakes

promptly when her baby cries.

What is long-term potentiation (LTP)?

§ LTP is an electrophysiological

measure of sustained increase

in synaptic efficacy when given

high-frequency stimulation

§ Cellular and behavioral studies

suggest that learning and

memory can be modeled by

LTP

Time (min)

-20 0 20 40 60 80 100 120 140 160 180

fEP

SP

slo

pe (

% c

han

ge o

f b

aselin

e)

0

50

100

150

200

250

300

Field EPSPs

High-frequency stimulation

Alzheimer’s Disease & Senile Dementia

§ Alzheimer’s disease is defined as premature aging of the

brain, usually beginning in mid-adult life and progressing

rapidly to extreme loss of mental powers—similar to that

seen in very, very old age.

§ AD is associated with accumulation of brain Beta-Amyloid

Peptide. The peptide accumulates in amyloid plaques found

in widespread areas of the brain. Thus, AD appears to be a

metabolic degenerative disease.

§ Vascular Disorders May Contribute to Progression of AD.

CEREBRAL DOMINANCE

AND LANGUAGE

Cerebral dominance§ The function of the speech and its control areas

are usually much more highly developed in one

cerebral hemisphere than in the other. This is

called the dominant hemisphere.

l concerned with sequential-analytic process

(categorical hemisphere)

l Its lesion: language disorders.

§ The other hemisphere: identification of objects

by form, recognition of musical theme

(representational hemisphere). Its damage

produces agnosia.

§ Related to handedness

Left and Right Hemisphere

§ The left hemisphere usually is the

dominant one. It excels in mathematical

ability, symbolic thinking, sequential

logic. The areas in temporal lobe

concerned with language ability.

§ Large number of artists, musicians are

left-handers.

Left and Right Hemisphere

Left-hemisphere:

§ Sequential analysis

l Analytical

l Problem solving

§ Language

Right-hemisphere:

§ Simultaneous analysisl Synthetic

§ Visual-Spatial skillsl Cognitive maps

l Personal space

l Facial recognition

l Drawing

§ Emotional functionsl Recognizing emotions

l Expressing emotions

§ Music

corpuscallosum

Unable to name the object in the left part of visual field

Able to identify the object and image

Split-brain

Epileptic activity spread

from one hemisphere

to the other through

corpus callosum

Since 1930, such epileptic

treated by severing the

interhemispheric

pathways

Verbal report ?

categorical

hemisphere

Handedness

§ In right-handed, 96% the left- dominant ,

remaining 4% the right-dominant.

§ In left-handed, 15% the right-dominant, 15%

not clear, 70% the left-dominant.

§ Dyslexia (impaired ability to learn and read,

12 times as common in left-handers as they

are in right-handers.

Physiology of Language§ Language is one of the fundamental

bases of human intelligence, a key part of

human culture.

§ Wernicke’s area is concerned with

comprehension of auditory/visual

information. Responsible for recognition &

construction of words.

Language areas

§ Located in a large area surrounding the left

(or language-dominant) lateral sulcus

§ Major parts

l Wernicke’s area

l Broca’s area

l Angular gyrus

• behind the Wernicke’s area

• processes information from words that are read

In 1908, Dr. Brodmann

numbered areas of cortex

according to cortical cell

arrangement. These

correspond with human

functions.

Areas 44, 45 (Broca’s

area) – Expressive speech

areas

Areas 41, 42 – Primary

auditory

Area 22 (Wernicke’s) –

receptive speech, auditory

perception comprehension

Wernicke’s Area (Brodmann’s 22)

§ in superior temporal gyrus, near auditory cortex

§ comprehension of auditory and visual information

(Receptive speech -- language comprehension)

§ projects to Broca’s area (via arcuate fasciculus)

§ Wernicke’s aphasia

l Fluent

l Syntactical but empty sentences, often make no sense

(contains many paraphasias)

l Used to be thought to be crazy

l Unable to understand what they read

or hear

Broca’s Area (Brodmann’s 44 & 45)

§ in frontal lobe, in front of the inferior motor

cortex

§ processes information into coordinated pattern

(Expressive speech)

§ projects the pattern to motor cortex

(vocalization)

§ Broca’s aphasia

l Nonfluent, labored, and hesitant speech

l Comprehension relatively intact (can understand)

Path taken by impulses when a subject names avisual object, projected on a horizontal section

PET scans of the left cerebral hemisphere

Nonhuman Primates

§ Vocalizations look preprogramed,

serving specific purposes only

§ Initiated by sub-cortical areas like limbic

system

§ But for vocalization and decoding, they

also use left hemisphere

Language Disorders

§ Egyptians reported

speech loss after blow

to head 3000 years ago

§ Broca (1861) finds

damage to left inferior

frontal region (Broca’s

area) of a language

impaired patient, in

postmortem analysis

Broca’s area

Wernicke’s area ( posterior end of the

superior temporal gyrus)

Angular gyrus

(area 39)

posterior part of intermediate frontal gyrus

W

S

H

V

S: motor aphasia

W: agraphia

H: sensory aphasia

V: alexia

Language disorders caused by lesions in the categorical hemisphere

Language Disorders

§ Nonfluent aphasia (Borca’s aphasia):

l Talking with considerable effort (Nonfluent speech)

§ Fluent aphasia

l Wernicke’s aphasia (Fluent speech but

unintelligible)

l Conduction aphasia (auditory cortex)

§ Anomic aphasia:

l Angular gyrus damage

§ Dyslexia

Dyslexia

§ Problem in learning to read

§ Common in boys and left-handed

§ High IQ, so related with language only

§ Postmortem observation revealed anomalies in the arrangement of cortical cellsl Micropolygyria: excessive cortical folding

l Ectopias: nests of extra cells in unusual location

§ Might have occurred in mid-gestation, during cell migration period

SUMMARY-terms

§ autonomic nervous system

§ vital centers

§ Circadian rhythms

§ Instinctual behavior

§ Evoked cortical potential

§ alpha block

§ Conditioned Reflex

§ dominant hemisphere

SUMMARY-questions

§ Function of ANS on the target organs

§ Hypothalamus regulation of visceral

function

§ Name two types of sleep, describe their

characteristics and the distribution of

sleep stages.

functions of the nervous...

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