Psychostimulants Depress Excitatory Synaptic Transmission ...
Synaptic Transmission - KTH
Transcript of Synaptic Transmission - KTH
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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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