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BIOL 2401Week 6

Nervous System

Collin County Community College

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Transmission at Synapses

Each neuron in the brain is believed to formabout 1000 synaptic endings. With around 1012

neurons in the brain, this yields a staggering1015 number of synapses and possiblepathways for impulses to travel.

Synapses are the site ofcommunication between 2 ormore neurons. It mediates thetransfer of information and itis the place where the signalare transmitted, blocked ormodulated.

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Synapses

• The neuron that sends the signal = pre-synaptic neuron• The neuron receiving the signal = post-synaptic neuron

• If the signal travels from axon to dendrite = axodendritic synapse

• If the signal goes from axon to cell body = axosomatic synapse

• If signal travels from axon to axon = axoaxonic synapse

Definitions

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SYNAPSES

There are two types of Synaptic transmission

1. Electrical Synapses• arriving impulse forces ions to flow through gap junctions

that connect to adjacent cells• electrical disturbance depolarizes the post- synaptic cell• they result in fast transmission and capable to

synchronize the activity of interconnecting cells

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2. Chemical Synapses

• This synapse is characterized by a synaptic cleftwhich separates the two neurons ( ~ 20-50 nm) …..So there is no physical connections

• Impulses cannot jump this cleft . That's why theorganization across a synapse is such that thepresymaptic neuron terminal contains vesicles withneurotransmitters ( the chemical signal) and thepostsynaptic neuron membrane contains the receptorproteins for this messenger

SYNAPSES

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In a chemical synapse, the presynaptic impulse whichis ionic in nature, is converted to a chemical signal(neurotransmitters) that crosses the cleft and influencethe chemically gated ion channels in the postsynapticneuron, and consequently the membrane potential inthat area.

SYNAPSES

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ACTIONS AT A SYNAPSE

DENDRITE

AXON

4. The binding of neurotransmitters to receptor proteins in the postsynaptic membraneis linked to an alteration in its ion permeability.

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1. Action potential,moving along axon’svoltage-gated Na+

and K + channels,arrives at terminal. Ca++

22. Actionpotential opensvoltage-gatedCa++ channels.

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3. Ca++ influxtriggersneurotransmitterrelease into thesynaptic cleft.

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ACTIONS AT POSTSYNAPTIC END

• The function of the neurotransmitters is to bind to aspecific receptor on the postsynaptic membrane

• Those receptors are chemically gated ion channels.

• The neurotransmitter is thus the chemical that will bind toan ion channel and result in a certain action.

• This action can be a local depolarization ; if this is thecase we are dealing with the creation of gradedpotentials.

• This action can however be a local hyperpolarization ; ifthis is the case we are preventing the creation ofgraded potentials.

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EPSP versus IPSP

Excitatory PostSynaptic Potential (EPSP)

• Is a depolarization created in the Postsynapticmembrane.

• It increases the possibility of having an A.P. in the axonof this neuron

Inhibitory PostSynaptic Potential (IPSP)

• Is a hyperpolarization created in the Postsynapticmembrane.

• It decreases the possibility of having an A.P. in the axonof this neuron

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An excitatory postsynaptic potential (EPSP) is a gradeddepolarization that moves the membrane potential closer tothe threshold for firing an action potential (excitement).

EPSP versus IPSP

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Neurons

An inhibitory postsynaptic potential (IPSP) is a gradedhyperpolarization that moves the membrane potential furtherfrom the threshold for firing an action potential (inhibition).

EPSP versus IPSP

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Graded depolarizations are typically the result of the inward movement of Na+

(but can result from Ca++ influx and/or decreased K+ efflux).

Graded hyperpolarizations are typically the result of the outward movement of K+

(but can result from decreased Na+ influx).

EPSP versus IPSP

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Signal Integration

Neurons receive asmany as 200,000 terminals.

Effect on initial membranesegment reflects anintegration of all activity atthat time.

It is an integration andsummming up of allEPSP’s and IPSP’s !

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The membrane potential of a real neuron typicallyundergoes many EPSPs (A) and IPSPs (B), since itconstantly receives excitatory and inhibitory input fromthe axons terminals that reach it.

Threshold refers to the minimum graded depolarizationthat initiates the cyclic activity of the voltage-gated Na+ and K+ channels, resulting in theinitiation of an action potential.

Signal Integration

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NEURONAL COMMUNICATION

Two types of signal summation

Temporal Summation

Spatial Summation

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Temporal Summation

• The same neuron “fires” quickly in succession• The result is more N.T. released and thus a bigger

graded potential• The same neuron releases always the same N.T.,

thus the effect is always similar

NEURONAL COMMUNICATION

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Spatial Summation

• Different neurons “fire” in quick in succession or atthe same time

• The result is more N.T. in the synaptic cleft• Each neuron releases it’s own N.T.; the effect is

not always similar

NEURONAL COMMUNICATION

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Panel 1: Two distinct, non-overlapping, graded depolarizations.Panel 2: Two overlapping graded depolarizations demonstrate temporal

summation.Panel 3: Distinct actions of stimulating neurons A and B demonstrate

spatial summation.Panel 4: A and B are stimulated enough to cause a suprathreshold graded

depolarization, so an action potential results.Panel 5: Neuron C causes a graded hyperpolarization; A and C effects

add, cancel each other out.

Temporal versus Spatial Summation

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Distance from stimulus

Where v.g. channels start

Graded potentials decay as they move over distance.

Threshold is reached

A.P. will start in axon

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Cholinergic Synapses

• These are synapses that use Acetylcholine (ACh) asNeurotransmitters

• They are the oldest studied and the best known• They are present in the Neuromuscular Junction

(NMJ), CNS, and PNS.• ACh in the NMJ always results in an EPSP in the

postsynaptic membrane because it opens chemicallygated Na+ channels

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Terminating the Signal at the Synapse

• At every synapse, the signal that started the events hasto be terminated

• If not, we would have continuous stimulation• For example, at a NMJ, this would mean a continuous

contraction of the skeletal muscle involved.• What we want is one signal ( EPSP above threshold) =

one contraction

• Neutrotransmitter becomes degraded by specific enzymes• Neurotransmitter diffuses out of the synapse area• Neurotransmitter is taken up be glial cells or by pre-synaptic

membrane (axon itslef)

Termination mechanisms

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Termination of the NT effect

Diffusion out of synaptic cleftRe-uptake for recycling by the axonterminals (requires specific transporters)

Breakdown by specific membraneslocated on postsynaptic membrane

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AcetylCholine-Esterase

• AcetylCholine Esterase (AChesterase) is a specificenzyme found on the postsynaptic membranes ofcholinergic synapses

• It functions to break down ACh into Acetate and Choline• Thus, from the moment ACh is releases in the synaptic

cleft, it is already being broken down• The axon then takes up the choline part and recycles it

back into Ach within the NT vesicles

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Acetate Choline

AcetylCholine-Esterase

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Cholinergic Synapses

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Modulation of Neurotransmitter Release

• Modulation of N.T. release refers to changing theamount of N.T. released into the synaptic cleft.

• The more (less) N.T. released that causesEPSP’s, the higher (lower) the probability of anA.P.

• The reverse holds true for N.T. that result inIPSP’s

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• A neuron that is brought closer to threshold is saidto be facilitated.

• The higher the degree of facilitation, the lessadditional stimuli needed to trigger an A.P.

Facilitation

Examples

Nicotine : stimulates ACh receptors

Caffeine : lowers the threshold for stimulation

Modulation of Neurotransmitter Release

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• A neuron that for examplecauses an IPSP at thepresynaptic membrane

• Or a neuron that releases aNT (Example is GABA) atthe presynaptic membranethat in turn closes v.g. Ca++channels

Presynaptic Inhibition

Modulation of Neurotransmitter Release

• Both situation will result in less Ca++ influx in the axonterminal and hence less exocytosis of NT vesicles !

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• A neuron that for examplecauses a prolongedopening of v.g. Ca++channels ( action ofseretonin at somesynapses)

Presynaptic Facilitation

Modulation of Neurotransmitter Release

• In this situation moreCa++ influx occurs intothe axon terminal andhence more exocytosis ofNT vesicles !

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AcetylCholine (Ach)

Examples of Neurotransmitters

Blocks Ach receptors andcauses paralysis in muscles

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Biogenic Amines

Examples of Neurotransmitters

These are N.T. derived from amino acids

The following are derived from Tyrosine

Also known as the catecholamines

Epinephrine = adrenaline

Dopamine is an important brain N.T.

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Amino Acids

Examples of Neurotransmitters

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Neuronal Afflictions

Heavy metal poisoning

• results in damage to neuroglia and demyelination• mercury, lead arsenic are the major ones

Multiple Sclerosis

• results demyelination of neurons in brain, spinal cord• believed to be a defect of the immune system

Tay Sachs Disease

• genetic abnormality that results in a build-up of gangliosides inlysosomes of neurons

• Results in destructions of neurons; children die at early age.

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Neuro-Toxins

Tetrodotoxin (TTX)

• found in Pufferfish(fugu) and somesalamanders

• very potent v.g. Na+

channel blocker

Saxitoxin

• found in some marine microorganisms (dinoflagellates)• some are responsible for “red tide” in seas• eating contaminated shellfish can result in paralytic shellfish

poisoning (mechanism is similar as TTX)

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Neuro-Toxins

Nerve gases and Insecticides

• Inhibit the function of ACh-esterase• Results in maintained contractions of muscles

such as diaphragm (person can’t exhaleanymore)

Atropine

• Competes with ACh for binding sites on receptor

tuboCurare

• Prevents binding of ACh to its receptor