what about communication between neurons?. presynaptic ending – ◦ portion of the axon conveying...

What about communication between neurons?

presynaptic ending – ◦ portion of the axon conveying information to

the next neuron

Some terms…….

presynaptic ending – ◦ the portion of the axon that is conveying

information to the next neuron

synapse or synaptic cleft◦ the space between neurons where

communication occurs

Some terms…….

presynaptic ending – ◦ the portion of the axon that is conveying

information to the next neuron

synapse or synaptic cleft◦ the space between neurons where

communication occurs postsynaptic membrane

◦ the portion of the neuron (usually dendrite) that receives information

Some terms…….

presynaptic ending – ◦ the portion of the axon that is conveying information to the

next neuron

synapse or synaptic cleft◦ the space between neurons where communication occurs

postsynaptic membrane

◦ the portion of the neuron (usually dendrite) that receives information

pre and postsynaptic receptors

◦ proteins in both the presynaptic and postsynaptic ending that allow for information to be transferred

Some terms…….

synaptic vesicles --small enclosed membranes that contain neurotransmitter - found in presynaptic ending

neurotransmitter – substance in vesicles that are released in synapse and convey info to the next neuron

Presynaptic ending

Postsynaptic ending

synapse

AP reaches presynaptic ending-

Ca+2 channels in presynaptic ending open and Ca+2 enters

What happens at level of synapse?

Ca+2 entry into the presynaptic ending critical for neurotransmitter release

Why are Ca+2 ions important?

drugs that block Ca+2 channels…….

protein embedded in membrane

mechanism for neurotransmitter to influence postsynaptic activity by binding to receptor

postsynaptic receptors

NT binds to postsynaptic receptors and causes small local changes in electrical potential (depolarizations or hyperpolarizations)-

◦ Called graded potentials

Summary

increase or decrease the likelihood of the neuron receiving info to generate an action potential◦ graded potentials that increase the likelihood of an action

potential are called EPSPs (excitatory postsynaptic potentials)

Graded Potentials

increase or decrease the likelihood of the neuron receiving info to generate an action potential◦ graded potentials that increase the likelihood of an action

potential are called EPSPs (excitatory postsynaptic potentials)

◦ graded potentials that decrease the likelihood of an action potential are called IPSPs (inhibitory postsynaptic potentials)

Graded Potentials

NT binding to postsynaptic receptors cause local ion channels to open

chemically dependent ion channels ◦ (in contrast with electrically dependent ion

channels in the axon)

How does the neurotransmitter cause EPSPs and IPSPs?

postsynaptic receptors open ion channels – ◦ ion channels in postsynaptic membrane (that we

need to worry about) include Na+, Cl- and K+

How does the neurotransmitter cause EPSPs and IPSPs?

EPSPs – excitatory postsynaptic potentials

- increase the likelihood of an AP

- opening of

IPSPs – inhibitory postsynaptic potentials

decrease the likelihood of an AP

- opening of

Two kinds of Graded Potentials

http://www.blackwellpublishing.com/matthews/neurotrans.html

Axon hillock

◦ graded potentials are summed at axon hillock and……if the sum is a great enough depolarization….

How do graded potentials result in an action potential?

action potential or

spike

Graded Potentials and AP differ in a number of ways

◦ AP – occurs at the axon◦ GP – occurs anywhere the neuron receives info

from another neuron (usually dendrite although NOT ALWAYS)

◦ action potentials are “all or none”graded potentials decrease over space and

time◦ Graded potentials are localized – has

impact in limited region; AP travels down the axon

Graded potentials vs action potentials

Graded potentials can either increase or decrease the likelihood of an action potential

Graded vs Action Potentials

Postsynaptic receptor and NT – think about a lock and key!

So what about these NT?

Neurotransmitter represents a keyReceptor represents the lock

1. directly opening the ion channel◦ occurs and terminates very quickly

2 ways that neurotransmitter exert these effects

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1. directly opening the ion channel◦ occurs and terminates very quickly

2. more indirect ◦ ultimately opens ion channel via stimulating a

chemical reaction takes longer but lasts longer

2 ways that neurotransmitter exert these effects

http://www.blackwellpublishing.com/matthews/neurotrans.html

1. reuptake - most common ◦ protein on presynaptic ending transports it back

into the neuron that released it◦ Means of recycling NT

saving energy (neurons have to synthesize or produce their own NT)

◦ a common way for drugs to alter normal communication

2 main ways for getting the neurotransmitter out of the synapse

cocaine, amphetamine, methylphenidate (Ritalin) – block reuptake of a number of NT – particularly dopamine (reward)

many of the newer antidepressants are SSRIs (selective serotonin reuptake inhibitors)

Examples of reuptake inhibitors

2. enzyme degradation ◦ enzyme - speeds up a reaction

◦ ex. acetylcholine (ACh)is a neurotransmitter is broken down by acetylcholinesterase (AChE) For ACh – this is done in the synapse

probably 100s of “putative” neurotransmitters – more being discovered all the time

role that the novel NTs play still being determined

Neurotransmitters

1. acetylcholine (ACh) –•

Some classic NT

acetylcholine (ACh) – found in CNS and PNS• receptor subtypes –

• nicotinic and muscarinic

Some classic NT

acetylcholine (ACh) – found in CNS and PNS• receptor subtypes –

• nicotinic and muscarinic

• nicotinic receptors – muscles

• acetylcholine also important for various behaviors including learning and memory alzheimers disease, REM sleep, among other things…

Some classic NTs

2. Monoamines

1. dopamine (DA)important for reward circuitsschizophrenia and Parkinsons disease

Neurotransmitters (cont)

2. Monoamines

1. dopamine (DA)

2. norepinephrine (NE)important for arousalaltered activity implicated in depression

Neurotransmitters (cont)

2. Monoamines

1. dopamine (DA)

2. norepinephrine (NE)

3. serotonin (5HT)aggression, anxiety, depression

Neurotransmitters (cont)

3. Peptides- really large neurotransmitters

Neurotransmitters (cont)

3. Peptides

1. substance Pimportant for pain

2. endorphins and enkephalins (endogenous opiates)

pain relievers!

Neurotransmitters (cont)

4. amino acids (tiny neurotransmitters)

1. glutamateALWAYS EXCITATORY (IE always causes EPSPs)

2. GABA –always inhibitory ( always causes IPSPs)-

Neurotransmitters (cont)

almost any aspect of the NT function can be affected by drugs!

How can drugs affect a neurotransmitter?

synthesis of NT storage of NT release of NT binding of NT breakdown of NT

So….

agonist – mimics the neurotransmitter’s effect

antagonist – blocks the neurotransmitter’s effect

What are possibilities?

acting like a receptor agonist◦ nicotine

ionotropic potent poison

acting like a receptor antagonist◦ curare

ACh as an example

con’t alter breakdown of ACh

blocks breakdown◦ mustard gases, insecticides, ◦ nerve gases

Sarin - estimated to be over 500 times more toxic than cyanide

◦ Gulf War Syndrome?◦ other current syndromes??

con’t alter breakdown of ACh

◦ blocks breakdown mustard gases, insecticides, physostigmine Gulf War Syndrome?

alter release of ACh◦ block release – botulism

con’t

alter release of ACh◦block release – botulism◦botox

◦stimulate release – black widow spider venom