Synapse and Neurotransmitter
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Transcript of Synapse and Neurotransmitter
Synapse and Synapse and NeurotransmitterNeurotransmitter
苏 擘苏 擘神经生物学研究所神经生物学研究所(( 66 号楼号楼 66206620 ) )
[email protected]@sdu.edu.cn
0531-883823290531-88382329
Cell Body (Soma)Cell Body (Soma):: Life SupportLife Support Protein SynthesisProtein Synthesis Single NucleusSingle Nucleus
Axon:Axon: Longest Longest process transmits process transmits messages away from messages away from cell bodycell body
Dendrites:Dendrites: Multiple Multiple processes off cell processes off cell body body –– receive receive messagesmessages
Neurons Structure & Function
Neurons Structure & Function
IntroductionIntroduction
Axons DendritesTake information away from
the cell bodyTake information to the cell
body
Smooth surfaceRough surface (dendritic
spines)
Generally only 1 axon per cell
Usually many dendrites per cell
No ribosome Have ribosomes
Can have myelin No myelin insulation
Branch further from the cell body
Branch near the cell body
Differences between Axons and Dendrites
EXCITABLE MembraneEXCITABLE Membrane: Able : Able to regulate the movement of ions to regulate the movement of ions (charges) across and along (charges) across and along membrane---membrane---SIGNAL SIGNAL TRANSDUCTIONTRANSDUCTION
Important Features of NeuronsImportant Features of Neurons
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OutlineOutline
Types of synapsesTypes of synapses
Signal transmission at chemical synapsesSignal transmission at chemical synapses
Principles of synaptic integrationPrinciples of synaptic integration
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Synapse:Synapse:
a specialized junction that a specialized junction that
transfers nerve impulse transfers nerve impulse
information between information between
neurons or neuron and neurons or neuron and
effector cells. effector cells.
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Electrical synapsesElectrical synapses Occur at specialized sites called Occur at specialized sites called gap junctiongap junction
Common in non-neural cells Common in non-neural cells (astrocytes) and early and early
embryonic stagesembryonic stages
Chemical synapsesChemical synapses Predominates in the mature human nervous systemPredominates in the mature human nervous system
Types of Synapses
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Axosomatic Axosomatic synanpsesynanpse
Axodendritic Axodendritic synapse synapse
Axoaxonic Axoaxonic synapsesynapse
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ElectricalElectrical SynapseSynapse
Gap junction– Adjacent cells electrically
coupled through a channel.
Ionic current
Cytoplasm continuous
No synaptic cleft
- 3.5nm
Brief delay
Bidirectional
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Rapid Transmission of Signal at Rapid Transmission of Signal at Electrical SynapsesElectrical Synapses
An action potential in the An action potential in the
presynaptic neuron causes presynaptic neuron causes
the postsynaptic neuron to the postsynaptic neuron to
be depolarized within a be depolarized within a
fraction of a millisecond. fraction of a millisecond.
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Gap junctionsGap junctions
Channels: Channels:
ConnexonConnexon
Diameter is 2nmDiameter is 2nm
6 subunits: 6 subunits:
connexinconnexin
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The chemical synapseThe chemical synapse is a specialized junction that is a specialized junction that transfers nerve impulse information from a presynaptic transfers nerve impulse information from a presynaptic membrane to a postsynaptic membrane membrane to a postsynaptic membrane using using neurotransmitters.neurotransmitters.
Axodendritic synapse Axosomatic synanpse Axoaxonic synapseAxodendritic synapse Axosomatic synanpse Axoaxonic synapse
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Chemical SynapsesChemical Synapses Presynaptic elementPresynaptic element
Synaptic vesiclesSynaptic vesicles
Active zoneActive zone
Synaptic cleftSynaptic cleft
Postsynaptic densityPostsynaptic density
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NeurotranmittersNeurotranmitters
20-50nm cleft20-50nm cleft
Syanptic delay:Syanptic delay:
1-5ms or longer1-5ms or longer
unidirectionalunidirectional
Chemical SynapsesChemical Synapses
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Chemical synapses Chemical synapses as seen with electron microscopeas seen with electron microscope
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Electrical SynapseElectrical Synapse Chemical SynapseChemical Synapse
Distance between pre- and Distance between pre- and postsynaptic cell postsynaptic cell
membranesmembranes
3.5nm3.5nm 20-50nm20-50nm
Cytoplasmic continuity Cytoplasmic continuity
between pre- and between pre- and
postsynaptic cellspostsynaptic cells
YesYes NoNo
Ultrastructural componentsUltrastructural components Gap-iunction channelsGap-iunction channels Presynaptic vesicles and Presynaptic vesicles and active zones; postsynaptic active zones; postsynaptic
receptorsreceptors
Agent of transmissionAgent of transmission Ion currentIon current Chemical transmitterChemical transmitter
Synaptic delaySynaptic delay Virtually absentVirtually absent Significant: at least 0.3 ms, Significant: at least 0.3 ms,
usually 1- 5 ms or longerusually 1- 5 ms or longer
Direction of transmissionDirection of transmission Usually bidirectionalUsually bidirectional unidirectionalunidirectional
Distinguishing Properties of Electrical and Chemical SynapsesDistinguishing Properties of Electrical and Chemical Synapses
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OutlineOutline
Types of synapsesTypes of synapses
Signal transmission at chemical synapsesSignal transmission at chemical synapses
Principles of synaptic integrationPrinciples of synaptic integration
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Signal transmission at chemical synapsesSignal transmission at chemical synapses
From a presynaptic membrane to a postsynaptic From a presynaptic membrane to a postsynaptic
membrane using neurotransmittersmembrane using neurotransmitters
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Signal Transmission at Chemical SynapsesSignal Transmission at Chemical Synapses
NeurotransmittersNeurotransmitters
NT ReceptorsNT Receptors
EPSP and IPSPEPSP and IPSP
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NeurotransmittersNeurotransmitters
Precursor transportPrecursor transport
SynthesisSynthesis
StorageStorage
ReleaseRelease
ActivationActivation
Termination Termination
diffusion, degradation, diffusion, degradation,
uptake, autoreceptorsuptake, autoreceptors
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ReleaseRelease
Quanta release Each vesicle contains one quanta of neurotransmitter (approximately
7000 molecules)
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Synthesis and StorageSynthesis and Storage
A: peptideA: peptide B: amine and amino acidB: amine and amino acid
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NT Receptors NT Receptors
Transmitter-gated ion channelsTransmitter-gated ion channels
G-protein-coupled receptorsG-protein-coupled receptors
AutoreceptorAutoreceptor
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AutoreceptorAutoreceptor
In the membrane of the In the membrane of the
presynaptic terminalpresynaptic terminal
G-protein-coupled G-protein-coupled
receptorsreceptors
Regulates NT release Regulates NT release
and synthesisand synthesis A
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①Neurotransmitter release at all
presynaptic terminals on a cell
results in receptor binding, which
causes the opening or closing of
specific ion channels.
②The resulting conductance
change causes current to flow,
which may change the membrane
potential.
③The postsynaptic cell sums (or
integrates) all of the EPSPs and
IPSPs, resulting in moment-to-
moment control of action potential
generation.
Events from neurotransmitter release to Events from neurotransmitter release to postsynaptic excitation or inhibitionpostsynaptic excitation or inhibition
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Excitatory postsynaptic potentialExcitatory postsynaptic potential (EPSP)(EPSP)
An AP arriving in the An AP arriving in the
presynaptic terminal presynaptic terminal
cause the release of cause the release of
neurotransmitterneurotransmitter
The molecules bind The molecules bind
and active receptor on and active receptor on
the postsynaptic the postsynaptic
membranemembrane
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Opening transmitter-Opening transmitter-
gated ions channels gated ions channels
( Na+) in postsynaptic- ( Na+) in postsynaptic-
membranemembrane
Both an electrical and a Both an electrical and a
concentration gradient concentration gradient
driving Na+ into the cell; driving Na+ into the cell;
The postsynaptic The postsynaptic
membrane will become membrane will become
depolarized (EPSP).depolarized (EPSP).
Excitatory postsynaptic potential (EPSP)Excitatory postsynaptic potential (EPSP)
58
Inhibitory postsynaptic potential (IPSP)Inhibitory postsynaptic potential (IPSP) A impulse arriving in the A impulse arriving in the
presynaptic terminal presynaptic terminal
causes the release of causes the release of
neurotransmitter;neurotransmitter;
The molecular bind and The molecular bind and
active receptors on the active receptors on the
postsynaptic membrane postsynaptic membrane
open CI- or, sometimes K+ open CI- or, sometimes K+
channels;channels;
More CI- enters, K+ outer More CI- enters, K+ outer
the cell, producing a the cell, producing a
hyperpolarization in the hyperpolarization in the
postsynaptic membrane.postsynaptic membrane.
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Excitatory Inhibitory
DepolarizationHyperpolarization
Na+ influx K+ efflux
or Cl- influx
more likely to fire less likely
EPSP IPSP
EPSPs & IPSPs’ differentiationsEPSPs & IPSPs’ differentiations
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Two categories of CNS synaptic Two categories of CNS synaptic membrane differentiationsmembrane differentiations
Type I synapses typically Type I synapses typically contact specialized contact specialized projections on the dendrites projections on the dendrites spines, less commonly spines, less commonly contact the shafts of contact the shafts of dendrites. dendrites.
Type II synapses often Type II synapses often contact the cell body.contact the cell body.
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Gray’sGray’s Type IType I
Excitatory synapses: Excitatory synapses: permeable to Napermeable to Na++ and K and K++ ((N-AchR)N-AchR)
Gray’s type I:Gray’s type I: Round synaptic vesiclesRound synaptic vesicles Large active zone (1-Large active zone (1-
2um2um22))
Wide synaptic cleft Wide synaptic cleft (30nm) (30nm)
Extensive postsynaptic Extensive postsynaptic dense regionsdense regions
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Gray’s Type IIGray’s Type II
Inhibitory synapses: Inhibitory synapses: permeable to Clpermeable to Cl--
(GABA, Glycine)(GABA, Glycine) Gray’s type II:Gray’s type II:
Flattened synaptic Flattened synaptic vesiclesvesicles
Small active zone (<1umSmall active zone (<1um22))
Narrow synaptic cleft Narrow synaptic cleft (20nm) (20nm)
Intensive postsynaptic Intensive postsynaptic dense regionsdense regions
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OutlineOutline
Types of synapsesTypes of synapses
Signal transmission at chemical synapsesSignal transmission at chemical synapses
Principles of synaptic integrationPrinciples of synaptic integration
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Most CNS neurons receive thousands of syanptic Most CNS neurons receive thousands of syanptic
inputs inputs that active different combinations of that active different combinations of
transmitter-gated ion channels and GPCRs.transmitter-gated ion channels and GPCRs.
The postsynaptic neuron integrates all of these The postsynaptic neuron integrates all of these
signals and give rise to a simple form of signals and give rise to a simple form of outputoutput: :
action potentials.action potentials.
Principles of Synaptic IntegrationPrinciples of Synaptic Integration
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Spatial summationSpatial summation
Temporal summationTemporal summation
EPSP SummationEPSP Summation
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Spatial summationSpatial summation
The adding together of EPSPs The adding together of EPSPs
generated simultaneously at generated simultaneously at
many different synapses on a many different synapses on a
dendrite.dendrite.
Two or more presynaptic inputs Two or more presynaptic inputs
are active at the same timeare active at the same time A space (spatial) dependent A space (spatial) dependent
process.process. Occurs in a Convergent Occurs in a Convergent
SynapseSynapse
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Temporal summationTemporal summation
The adding together of EPSPs The adding together of EPSPs
generated at the same synapse if generated at the same synapse if
they occur in rapid succession, they occur in rapid succession,
within 1-15 msec of one another.within 1-15 msec of one another.
The same presynaptic fiber fires AP The same presynaptic fiber fires AP
in quick successionin quick succession
A Time (Temporal) dependent A Time (Temporal) dependent
processprocess
Occurs in a Divergent SynapseOccurs in a Divergent Synapse
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Summation of postsynaptic potentials
EPSPs & IPSPs EPSPs & IPSPs summatesummate
CANCEL EACH CANCEL EACH OTHEROTHER
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Divergent synapse and convergent synapseDivergent synapse and convergent synapse
Synaptic InhibitionSynaptic Inhibition
Synaptic FacilitationSynaptic Facilitation
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Divergent SynapseDivergent Synapse A junction that occurs between a presynaptic neuron and A junction that occurs between a presynaptic neuron and
two or more postsynaptic neurons (ratio of pre to post is two or more postsynaptic neurons (ratio of pre to post is less than one).less than one).
The stimulation of the The stimulation of the
postsynaptic neurons depends postsynaptic neurons depends
on on temporal summation.temporal summation.
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Presynaptic neurons
Postsynaptic neuron
Convergent SynapseConvergent Synapse
A junction between two or more A junction between two or more
presynaptic neurons with a presynaptic neurons with a
postsynaptic neuron (the ratio of postsynaptic neuron (the ratio of
pre to post is greater than one).pre to post is greater than one).
The stimulation of the postsynaptic The stimulation of the postsynaptic
neuron depends on the neuron depends on the spatial spatial
summation.summation.
73
Synaptic InhibitionSynaptic Inhibition
Presynaptic inhibitionPresynaptic inhibition Postsynaptic neuron Postsynaptic neuron
produce decreased produce decreased
EPSPEPSP
Postsynaptic inhibitionPostsynaptic inhibition Postsynaptic neuron Postsynaptic neuron
produce IPSPproduce IPSP
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Presynaptic inhibitionPresynaptic inhibition
The inhibition occurs at the The inhibition occurs at the
presynaptic terminals before the presynaptic terminals before the
signal ever reaches the synapsesignal ever reaches the synapse
C and A form an axon-axon C and A form an axon-axon
synapse (presynaptic synapse). synapse (presynaptic synapse).
Neuron C has no direct effect on Neuron C has no direct effect on
neuron B, but it exert a neuron B, but it exert a
presynaptic effect to decrease presynaptic effect to decrease
the amount of neurotransmitter the amount of neurotransmitter
released from A.released from A.
C A
B
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Excitatory Synapse
• A activeA active
• B more likely to fire B more likely to fire
• Add a 3rd neuron ~Add a 3rd neuron ~
A B+
Presynaptic Inhibition
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Excitatory Synapse
A B+
Presynaptic Inhibition
C
-
• C activeC active
• less NT from A when activeless NT from A when active
• B less likely to fire ~B less likely to fire ~
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Postsynaptic inhibitionPostsynaptic inhibition
Effect of inhibitory synapses on the Effect of inhibitory synapses on the postsynaptic membranepostsynaptic membrane Inhibitory interneuron release inhibitory transmitters Inhibitory interneuron release inhibitory transmitters
and the postsynaptic neuron produce IPSPand the postsynaptic neuron produce IPSP
Afferent collateral inhibition (reciprocal Afferent collateral inhibition (reciprocal
inhibition)inhibition) Recurrent inhibitionRecurrent inhibition
79
Reciprocal inhibitionReciprocal inhibition
Afferent fibers excites the motor neurons to extensor Afferent fibers excites the motor neurons to extensor
muscle. And its branches excite an interneuron, which muscle. And its branches excite an interneuron, which
secrete the inhibitory transmitter at synapses on the secrete the inhibitory transmitter at synapses on the
motor neurons to flexor muscle (IPSP)motor neurons to flexor muscle (IPSP)
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Recurrent inhibitionRecurrent inhibition Neurons may also inhibit Neurons may also inhibit
themselves in a negative themselves in a negative
feedback fashion.feedback fashion.
Each spinal motor neuron Each spinal motor neuron
regularly gives off a recurrent regularly gives off a recurrent
collateral that synapses with collateral that synapses with
an inhibitory interneuron an inhibitory interneuron
(Renshaw cell) which (Renshaw cell) which
terminates on the cell body terminates on the cell body
of the spinal neuron and of the spinal neuron and
other spinal motor neurons to other spinal motor neurons to
slow and stop the discharge slow and stop the discharge
of the motor neuron.of the motor neuron.
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Synaptic FacilitationSynaptic Facilitation
Presynaptic Presynaptic facilitationfacilitation
Postsynaptic facilitationPostsynaptic facilitation
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Presynaptic facilitationPresynaptic facilitation
The structure is similar to The structure is similar to
presynaptic inhibition. presynaptic inhibition.
But the effect is increase But the effect is increase
the amount of NTs the amount of NTs
released from A.released from A.
C A
B
facilitation
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Excitatory Synapse
• A activeA active
• B more likely to fire ~B more likely to fire ~
A B+
Presynaptic Facilitation
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Excitatory SynapseExcitatory Synapse
A B+
Presynaptic FacilitationPresynaptic Facilitation
C
+
• C active (excitatory)C active (excitatory)• moremore NT from A when active NT from A when active
(Mechanism:(Mechanism:AP of A is AP of A is prolonged and Ca prolonged and Ca 2+2+ channels are channels are open for a longer period.)open for a longer period.)
• B B moremore likely to fire ~ likely to fire ~
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Postsynaptic facilitationPostsynaptic facilitation
EPSP summationEPSP summation Postsynaptic neuron that has been partially Postsynaptic neuron that has been partially
depolarized is more likely to undergo AP.depolarized is more likely to undergo AP.
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Synaptic PlasticitySynaptic Plasticity
synaptic plasticitysynaptic plasticity is the ability is the ability of the of the synapse between two between two neurons to change in to change in strength in in response to either use or disuse response to either use or disuse of transmission over synaptic of transmission over synaptic pathways.pathways.
Long-term potentiation (LTP)Long-term potentiation (LTP) Long-term depression (LTD)Long-term depression (LTD)
LTP, LTD LTP, LTD 为海马学习与记忆的分为海马学习与记忆的分子基础。子基础。