D_G_S_I_N

1. U S O I

2. U O M A

3. E O I T

4. O G U U

Neural Control

2011 Spring

Lecture 38: Introduction to the Nervous System

4. How do neurons pass information along the length of the neuron? That is, how does an action potential propagate?

5. How do neurons communicate with other neurons or effectors?

1. Who has nerves?

2. What do nerves do?

3. Neuron design?

Multi-cellular Organism

Information highways

1. Hormones – slow

2. Neurons - fast

Why care about the nervous system?

• Below: Components of the animal mechanism for maintaining homeostasis in response to a change in internal environmental conditions.

RECEPTOR(e.g., nerve)

INTEGRATOR(e.g., brain)

EFFECTOR(e.g., gland)

Stimulus

Response (change)feedback

• Nervous system plays key role as receptors, pathways for transmitting information, integration and relaying commands for response by effector.

What is the nervous system?

• Organ system that

•detects stimuli

•integrates information and

•relays commands

• Fundamental units of forming tissues and organs: ∙ neurons

∙ glial cells

• In complex organisms, responsible for memory.

What organisms actually use a nervous system to detect and respond to stimuli?

• All living organisms detect & respond to stimuli

• Nervous system can only exist in multicellular organisms (select groups within Eukarya) but which ones?

MolluscaAnnelidaBrachiopodaGymnolaemataNematodaArthropodaRotiferaTrematodaEchinodermataUrochordataCephalochordataCraniataCnidariaCtenophora

Porifera

After Valentine (2005)

Animals

Sea

Anemone

‘lowest’

organisms to

have a nervous

system

What are the three general classes of neurons?

• 1. Sensory neurons

∙ Detect stimulus & relay stimulus to interneurons

• 2. Interneurons

∙ Integrators of information from sensory neurons

• 3. Motor neurons

∙ communicates signal to effectors

∙ signal can be;

∙ inhibitory ∙ excitatory

Organization in Higher Animals –Humans too

• Nervous System

– Central Nervous System

• Brain

• Spinal Cord

– Peripheral Nervous System

• Somatic – Control over muscles

• Autonomic

– Sympathetic

– Parasympathetic

What is the structure of a neuron cell? How does it reflect its function?

• 4 major zones:∙ 1. Input zone - composed of

dendrites

cell bodyINPUT ZONE

Fig 34.6

Motor neuron

∙ dendrites – cytoplasmic extensions receive signals (input)

∙ cell body – dendrites extend from cell body

What is the structure of a neuron? How does it reflect its function?

∙ 2. Trigger zone – patch of membrane adjoining input zone where input becomes encoded into ‘action potential’ if stimulus sufficiently large

dendrites

cell body

TRIGGER ZONE

INPUT ZONE

CONDUCTING ZONE

axon

Fig 34.6

Motor neuron

∙ 3. Conducting zone – ‘wire’ delivers signal from input location (where cell body /dendrites are) to destination location where axon terminates

∙ axon – cytoplasmic extension which propagates signal received at input (if strong enough) in form of ‘action potential’

∙ 4. Output zone – composed of

dendrites

cell body

TRIGGER ZONE

INPUT ZONE

CONDUCTING ZONE

OUPUT ZONEaxon

axon

endingsFig 34.6

Motor neuron

∙ Branched ending of many axons where action potential is converted to a chemical signal to be passed to neighboring cells

What is the structure of a neuron? How does it reflect its function?

Where is the longest human neuron?

• Answer: Base of spine to toe!

• Over 1m long

• Giant Squid neurons

How does a neuron (any neuron) pass along a signal?

• Involves 2 steps:

∙ no action potential, no signal propagation

1) input must generate an action potential (AP)

2) Action potential induces release of neurotransmitters

at output zone

∙ AP originates at trigger zone as a result of stimulus

received at input zone

∙ travels along axon to output zone

∙ neurotransmitters are chemicals released from axon endings

∙ generates response in next neuron or cells of effector

What is an action potential (AP)? How are they caused? How do they work?

• self-propagating electrical signal caused by an abrupt reversal in the voltage difference across a plasma membrane of a neuron

∙ At rest neurons (ie. unstimulated) maintain an electrical gradient across plasma membrane = resting potential = -70 mV

What is the electrochemical structure of the neuron? How does this enable an action potential?

Fig 34.8 Cytoplasm

Interstitial fluid

Plasma membrane

What causes this charge difference (i.e. resting potential)?

• Due to creation & maintenance of differences in concentration of potassium (K+) and sodium (Na+) ions on inside and outside of membrane

∙ Sodium higher outside ∙ Potassium higher inside

What creates the Na+ and K+ gradients in the first place?

• Sodium-potassium pump – a transmembrane protein that pumps Na+ ions to the outside and K+ ions into the inside (cytoplasm)

∙ Na+/K+ pumps require ATP = active transport∙ 3 Na pumped for every 2 K allowed in!

Na+/K+ pump

Interstitial fluid

(outside)

CytoplasmK+ pumped in

Na+ pumped out

Na+K+

Na+

K++

-

Plasma membrane -70mV

Why don’t Na+ and K+ flow back (into/out of the cell) along their concentration gradients? i.e. What maintains these gradients?

• K+ and Na+ can only move through channels (transport proteins), not plasma membrane

Passive transporters with voltage-sensitive gated channels

Lipid bilayer of neuron membrane

Interstitial fluid

Cytoplasm

a) Na+ movement controlled by passive transporters with voltage sensitive gated channels that are closed when neuron at rest.

∙ There is always the tiniest bit of Na+ leaking into cell via incompletely sealed channels

Na+

Na+leaking

+

-

Passive transporters with open channels

Interstitial fluid

Cytoplasm

b) K+ can only move via passive transporters with open channels

Na+

Na+K+

K+

∙ K+ can diffuse out of cell along concentration gradient when cell at rest

∙ BUT movement out makes cytoplasm slightly more negative attracting some K+ back into the cell

∙ K+ concentration gradient maintained by balance btw diffusion out and diffusion back in due to electrical gradient

+

-

Why don’t Na+ and K+ flow back (into and out of the cell) along their concentration gradients? I.e. What maintains these gradients?

So what maintains these gradients in neuron at rest despite the leaking?

Na+

Na+K+

K+ +

-

Interstitial fluid

CytoplasmK+ pumped in

Na+ pumped out

• Na+/K+ pumps which return leaked Na+ ions to the outside (and some K+ ions to the inside) to maintain the gradients and thus the voltage difference across the plasma membrane.

• Stimulus elicits an electrical disturbance in input zone.

∙ Causes some Na+ ions to flow into the neuron.

∙ If stimulus is intense enough or lasts long enough, disturbance reaches the trigger zone.

∙ Trigger zone is rich with gated sodium channels, creating potential for mass diffusion of Na+ down concentration & electrical gradients.

What determines whether or not an action potential occurs?

dendrites

cell body

TRIGGER ZONE

INPUT ZONE

CONDUCTING ZONE

OUPUT ZONEaxon

axon

endings

Motor neuron

• 1. Disturbance strong enough to elicit action potential.

∙ Happens when enough sodium channels open in trigger zone to trigger positive feedback loop leading more channels to open.

What can happen once the electrical disturbance reaches the trigger zone?

Na+ in

Cytoplasm becomes more positive

Causes more voltage gatedNa+ channels to opencytoplasm

Interstitialfluid

∙ Called depolarization - charge difference across membrane decreasing, i.e. not so polarized – value increasing from -70 to -10 to + 30

• Positive feedback loop initiated once reach threshold levelmembrane potential (i.e. depolarized to threshold potential).

What determines if sufficient depolarization to set positive feedback loop in motion?

∙ At threshold, Na+ gates opening because of positive feedback, no longer depends upon strength or duration of stimulus.

∙ Once reach threshold, positive feedback ensures action potential will happen.

• 2. What happens if stimulation of input zone is not sufficient to cause enough depolarization to reach threshold in trigger zone?

What can happen once the electrical disturbance reaches the trigger zone?

∙ action potential will not happen

∙ too few Na+ crossed the membrane to initiated positive feedback loop

∙ What restores resting potential?

Fig 34.9

∙ neuron will be returned to resting potential.

• Discovered gene that results in an inability to sense pain in family in Pakistan (Nature. 2006. 444: 831)

What is an example of a phenotype that results from inability to trigger an action potential?

∙ Individuals with condition (homozygous recessive) injure themselves all the time because lack signal that tissue damaged.

Why feel no pain?

• mutation in gene coding for Na+ channel in nerves responsible for pain detection.

∙ mutation results in non-functional Na+ channel

∙ unable to trigger action potential in pain neurons

• mutation in same gene causes over sensitivity to stimuli causing erythromelalgia – severe pain in response to mild stimuli, ex. mild warmth

• Enough sodium gates open to reverse membrane potential: - outside, + inside.

• With voltage reversal,

What happens after threshold reached to complete action potential?

∙ K+ diffuses out along concentration and electrical gradient

∙ Na+ gates close

∙ K+ gates open = gated K+ channel, differs from open channel responsible for resting potential

Fig 34.8

∙ Restores voltage difference to + outside & - inside (actually overshoots a bit).

K+

Na+

-

+

Fig 34.8

Another action potential cannot immediately occur in this location. Why?

• Voltage gated Na+ channels have refractory period.

∙ Brief time when Na+ gates cannot open again after they have opened and closed in course of previous action potential.

• Preceding about processes taking place in one location of membrane.

What causes the action potential to move along the axon away from the trigger zone?

• Disturbance caused by action potential in one part of membrane, initiates action potential at adjacent site.

• So signal is passed down axon from trigger zone to output zone as a series of action potentials, one initiating the next.

So how is the signal propagated down the axon?

Trigger zone Output zone

Team Questions: 5 points:A poison that specifically disables the Na+/K+ pumps is added to a

culture of neurons. What effect does this eventually have on the

neurons?

a) The resting membrane potential goes to

zero.

b) The inside of the neuron would become

more negative relative to the outside.

c) The inside of the neuron would become

positively charged relative to the outside.

d) Sodium would diffuse out of the cell and

potassium would diffuse into the cell.

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Team Questions: 5 points:

A(n) ___ in Na+ permeability and/or a(n) ___ in K+ permeability

across a neuron’s plasma membrane would cause a shift in the

membrane potential from -70 mV to -80mV.

a) increase; increase

b) increase; decrease

c) decrease; increase

d) decrease; decrease

e) none of the above

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Presynaptic cell

Postsynaptic cell

How is signal communicated from cell to cell?

• Signal must be passed from neuron to another neuron (ex. from sensory neuron to interneuron) or to an effector. How?

∙ Joint between output zone of one neuron and input zone of another neuron or between output zone & plasma membrane an effector cell.

What is a chemical synapse? Fig 34.10

Postsynaptic cell’s plasma membrane

Presynaptic cell

Synaptic cleft = gap

What happens when the action potential reaches the output zone?

• Action potential typically causes neuron to release molecules of a class of biochemicals called a neurotransmitters from synaptic vessel.

∙ Ex. serotonin, dopamine, melatonin

• Synaptic vessels fuse with plasma membrane of presynaptic cell & release neurotransmitter into synaptic cleft.

synaptic

vesicle

membrane

receptor

synaptic

cleft

Fig 34.10

What does the neurotransmitter do?

• Diffuses across synapse & binds to receptors on plasma membrane of postsynaptic cell, which opens ion channels.

∙ Ions (ex. Ca++, Na+, K+) diffuse into postsynaptic cell

neurotransmitter

receptor for neurotransmitter

gated channel protein

(postsynaptic cell)

∙ Biochemical signal converted back into electrical signal = flowing ions.

Ions (in synaptic cleft)

How do these ions affect the postsynaptic cell?

• May have excitatory effect on postsynaptic cell

∙ Act to depolarize membrane and thus, increase chances that trigger zone will receive sufficient stimulation to drive it to the threshold and initiate action potential.

∙ Move membrane farther away from threshold – increase polarization = hyperpolarization – reduce chances of action potential.

• May have inhibitory effect on postsynaptic cell

What determines whether postsynaptic cell is excited or inhibited?

∙ Ex. GABA and valium

• Type & concentration of neurotransmitter

• Number & type of receptors

• Number & type of voltage gated channels

• Type of cell it is

Which of the following choices best describes

what is happening at step four in the graph

below?

1. Some Na channels close.

2. Most Na channels open.

3. Some K channels close.

4. Most K channels open.

5. Na/K pumps are inactivated.

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