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Synaptic Transmission_______________

Postsynaptic Mechanisms

Part I

• Synapseselectrical and chemical

• Neurotransmitterscategories and life cycle

• Neurotransmittersexamples and postsynaptic effects

• Pathology

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Part II

• Neurotransmitter Receptorscategories and examples

• Postsynaptic PotentialsEPSP and IPSP

Electrical Neurotransmission Chemical Neurotransmission

Can be modulated in many more

ways

Modulation possible

Often more complicated, receptor-

dependent effects

Relatively simple effects

One-directionalTwo-directional

Comparatively slowFast

No direct contact between cellsDirect contact between cells

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Electrical

synapse

Gap junctions

Hexameric structures

made of subunits called

connexons

Direct contact between cells – bidirectional transmission

Relatively uncommon in higher mammals

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Chemical Signaling Mechanisms

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Chemical Signaling Mechanisms

Chemical Neurotransmission

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1. Action potential depolarizes synaptic terminal

2. Calcium influx

3. Synaptic vesicles containing neurotransmitter fuse with

the presynpatic membrane

4. Neurotransmitter is released into the synaptic cleft

Depending on the type of neurotransmitter andpostsynaptic receptor a multitude of postsynapticeffects result…

What happens on the presynaptic side?

Presence Release Specific Receptors

Neurotransmitter

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Calcium-Dependent Transmitter Release

Neurotransmitters

Small-moleculeNeurotransmitters

Small molecular size1 amino acid, other type of moleculeRapid synaptic actions

Neuropeptides

Large molecular size3-36 amino acidsSlower, ongoing synaptic actions

Neurons often release more than one type of neurotransmitter

Biogenic aminesSub-group of similar chemicalproperties

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•Synthesis

•Packaging

•Release

•Removal

Neurotransmitter Life Cycle

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Small-Molecule Neurotransmitters

Small-Molecule Neurotransmitters

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Neuropeptides

Neuropeptides

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Prolonged excitatory neurotransmission mediated by glutamatecan destroy neurons.

Excitotoxicity

Under normal conditions the glutamate concentration in thesynaptic cleft reaches approx. 1mM. But only for a few milliseconds.

During brain injury excessive amounts of glutamate can be releasedand/or re-uptake mechanisms inhibited.Example: stroke

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Drug-induced imbalance of neurotransmitter release, responseand/or re-uptake

Addiction

Example: cocaine effects based on increased dopamine levelsin brain regions involved in motivation and emotionalreinforcement

Chemical Neurotransmission

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Postsynaptic Neurotransmitter Receptors(protein molecules)

Ionotropic ReceptorsLinked directly to ion channels

2 functional domains combined inone molecular entity:Extracellular transmitter bindingsiteMembrane-spanning ion channel

Multimers of 4 or 5 proteinsubunits, each contributing to thechannel pore

Metabotropic ReceptorsReceptors don’t contain ion channels

Channels affected by intermediatedmolecules (G-Proteins)

Monomeric proteins withextracellular transmitter binding siteand intracellular G-Protein bindingsite

Neurotransmitter binds, G-Proteinactivates, dissociates from receptor,interacts with ion channel or othereffector proteins

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Ionotropic Receptors

Metabotropic Receptors

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Ionotropic Receptors

Ionotropic Receptors

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Metabotropic Receptors

Metabotropic Receptors

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Activation of Postsynaptic Receptors Results in PSPs

Ionotropic Receptors

Mediate rapid postsynaptic effects

Arise 1-2 ms after AP reachespresynaptic terminal

Last a few tens of ms

Metabotropic Receptors

Mediates slower responses

Hundreds of ms to minutes orlonger

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Activation of Ach Receptors atNeuromuscular Synapses

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Na+ and K+ Movements DuringEPCs and EPPs

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Postsynaptic potential determines relative ion fluxes

ReversalPotential

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Excitatory and Inhibitory Postsynaptic Potentials

EPSPs

Depolarize postsynaptic cell andincrease probability of APgeneration

IPSPs

Hyperpolarize postsynapticcell and decrease probabilityof AP generation

The relationship of reversal and threshold potential determinesif a PSP is excitatory or inhibitory.

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Summation of Postsynaptic Potentials

PSPs resulting from the activity of single synapses are almostalways well below the threshold potential.

But neurons are commonly innervated by thousands ofsynapses. Therefore summation of PSPs in space and timeoccurs.

Summation allows the neuron to integrate all the electricalinformation provided by all the excitatory and inhibitorysynapses innervating it.

The balance between excitation and inhibition thereforedetermines AP generation.

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