synapse and neurotransmitter

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Synapse and Neurotransmitter. 苏 擘 神经生物学研究所 ( 6 号楼 6620 ) bxs103@sdu.edu.cn 0531-88382329. Synapse and Synaptic Transmission. Neurons Structure & Function. Introduction. Cell Body (Soma) : Life Support Protein Synthesis Single Nucleus - PowerPoint PPT Presentation

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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 ) )

bxs103@sdu.edu.cnbxs103@sdu.edu.cn

0531-883823290531-88382329

2

Synapse and Synapse and Synaptic Transmission Synaptic Transmission

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

Neurons

6

7

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

Action Potenti

al

Action Potenti

al

13

OutlineOutline

Types of synapsesTypes of synapses

Signal transmission at chemical synapsesSignal transmission at chemical synapses

Principles of synaptic integrationPrinciples of synaptic integration

14

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.

15

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

Gray’sGray’s Type I Gray’s Type IIType I Gray’s Type II

17

18

ElectricalElectrical SynapseSynapse

Gap junction– Adjacent cells electrically

coupled through a channel.

Ionic current

Cytoplasm continuous

No synaptic cleft

- 3.5nm

Brief delay

Bidirectional

19

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.

20

Gap junctionsGap junctions

Channels: Channels:

ConnexonConnexon

Diameter is 2nmDiameter is 2nm

6 subunits: 6 subunits:

connexinconnexin

21

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

22

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

24

Chemical synapses Chemical synapses as seen with electron microscopeas seen with electron microscope

25电镜冰冻蚀刻技术显示突触结构

26

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

31

PresynapticAxon Terminal

PostsynapticMembrane

Terminal Button Dendritic

Spine

32

(1) Precursor Transport

33

_ _ _

NT

(2) Synthesis

enzymes/cofactors

34

(3) Storage

in vesicles

35

Synapse

Vesicles

NT

Terminal Button Dendritic

Spine

36

Synapse

Terminal Button Dendritic

Spine

(4) Release

Receptors

37

Synapse

Terminal Button Dendritic

Spine

AP

38

Ca2+

Exocytosis

39

ReleaseRelease

Quanta release Each vesicle contains one quanta of neurotransmitter (approximately

7000 molecules)

40

(5) Activation

41

(6) Termination

42

(6.1) Termination by... Diffusion

43

(6.2) Termination by...Enzymatic degradation

44

(6.3) Termination by... Reuptake

45

(6.4) Termination by... Autoreceptors

A

46

Synthesis and StorageSynthesis and Storage

A: peptideA: peptide B: amine and amino acidB: amine and amino acid

47

A model for Ca2+-triggered vesicle fusion

48

Ca2+

CAMCAMKII

49

A electron microscopy view of NT release

50

Fine structure of vesicle fusion sitesFine structure of vesicle fusion sites

51

NT Receptors NT Receptors

Transmitter-gated ion channelsTransmitter-gated ion channels

G-protein-coupled receptorsG-protein-coupled receptors

AutoreceptorAutoreceptor

52

Transmitter-gated ion channelsTransmitter-gated ion channels

53

G-protein-coupled receptors (GPCR)G-protein-coupled receptors (GPCR)

54

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

55

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

56

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

57

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.

59

Excitatory Inhibitory

DepolarizationHyperpolarization

Na+ influx K+ efflux

or Cl- influx

more likely to fire less likely

EPSP IPSP

EPSPs & IPSPs’ differentiationsEPSPs & IPSPs’ differentiations

60

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.

61

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

62

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

63

OutlineOutline

Types of synapsesTypes of synapses

Signal transmission at chemical synapsesSignal transmission at chemical synapses

Principles of synaptic integrationPrinciples of synaptic integration

64

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

65

Spatial summationSpatial summation

Temporal summationTemporal summation

EPSP SummationEPSP Summation

66

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

67

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

68

Summation of postsynaptic potentials

EPSPs & IPSPs EPSPs & IPSPs summatesummate

CANCEL EACH CANCEL EACH OTHEROTHER

69

- 70mv

+

-

-

EPSP

IPSP

+

70

Divergent synapse and convergent synapseDivergent synapse and convergent synapse

Synaptic InhibitionSynaptic Inhibition

Synaptic FacilitationSynaptic Facilitation

71

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.

72

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

74

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

75

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

76

Excitatory Synapse

• Axon-axon synapse

• C is inhibitory ~

A B+

Presynaptic Inhibition

C

-

77

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 ~

78

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)

80

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.

81

Synaptic FacilitationSynaptic Facilitation

Presynaptic Presynaptic facilitationfacilitation

Postsynaptic facilitationPostsynaptic facilitation

82

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

83

Excitatory Synapse

• A activeA active

• B more likely to fire ~B more likely to fire ~

A B+

Presynaptic Facilitation

84

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 ~

85

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.

86

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。

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