How do neurons communicate?

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What about communication between neurons?
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Some terms.

• presynaptic ending
• portion of the axon conveying information to the
  next neuron

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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

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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

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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

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• 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

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Presynaptic ending
synapse
Postsynaptic ending
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What happens at level of synapse?

• AP reaches presynaptic ending-
• Ca2 channels in presynaptic ending open and Ca2
  enters

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Why are Ca2 ions important?
Ca2 entry into the presynaptic ending critical
for neurotransmitter release
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drugs that block Ca2 channels.
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postsynaptic receptors

• protein embedded in membrane
• mechanism for neurotransmitter to influence
  postsynaptic activity by binding to receptor

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Summary

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

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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)

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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)

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How does the neurotransmitter cause EPSPs and
IPSPs?

• 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)

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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

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Two kinds of Graded Potentials

• EPSPs excitatory postsynaptic potentials
• - increase the likelihood of an AP
• - opening of
• IPSPs inhibitory postsynaptic potentials
• decrease the likelihood of an AP
• - opening of

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Axon hillock
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How do graded potentials result in an action
potential?

• graded potentials are summed at axon hillock
  andif the sum is a great enough
  depolarization.

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action potential or spike
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Graded potentials vs action potentials

• 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

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Graded vs Action Potentials

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

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So what about these NT?

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

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Neurotransmitter represents a key Receptor
represents the lock
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2 ways that neurotransmitter exert these effects

• directly opening the ion channel
• occurs and terminates very quickly

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2 ways that neurotransmitter exert these effects

• directly opening the ion channel
• occurs and terminates very quickly
• more indirect
• ultimately opens ion channel via stimulating a
  chemical reaction
• takes longer but lasts longer

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2 main ways for getting the neurotransmitter out
of the synapse

• 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

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Examples of reuptake inhibitors

• 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)

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• 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

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Neurotransmitters

• probably 100s of putative neurotransmitters
  more being discovered all the time
• role that the novel NTs play still being
  determined

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Some classic NT

• acetylcholine (ACh)

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Some classic NT

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

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Some classic NTs

• 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

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Neurotransmitters (cont)

• Monoamines
• dopamine (DA)
• important for reward circuits
• schizophrenia and Parkinsons disease

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Neurotransmitters (cont)

• Monoamines
• dopamine (DA)
• norepinephrine (NE)
• important for arousal
• altered activity implicated in depression

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Neurotransmitters (cont)

• Monoamines
• dopamine (DA)
• norepinephrine (NE)
• serotonin (5HT)
• aggression, anxiety, depression

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Neurotransmitters (cont)

1. Peptides- really large neurotransmitters

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Neurotransmitters (cont)

• Peptides
• substance P
• important for pain
• 2. endorphins and enkephalins (endogenous
  opiates)
• pain relievers!

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Neurotransmitters (cont)

• 4. amino acids (tiny neurotransmitters)
• glutamate
• ALWAYS EXCITATORY (IE always causes EPSPs)
• 2. GABA
• always inhibitory ( always causes IPSPs)
• -

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How can drugs affect a neurotransmitter?

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

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So.

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

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What are possibilities?

• agonist mimics the neurotransmitters effect
• antagonist blocks the neurotransmitters effect

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ACh as an example

• acting like a receptor agonist
• nicotine
• ionotropic
• potent poison
• acting like a receptor antagonist
• curare

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cont

• 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??

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cont

• alter breakdown of ACh
• blocks breakdown
• mustard gases, insecticides, physostigmine
• Gulf War Syndrome?
• alter release of ACh
• block release botulism

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cont

• alter release of ACh
• block release botulism
• botox
• stimulate release black widow spider venom