Synapse and Neurotransmitter 6 6620 bxs 103sdu edu

Synapse and Neurotransmitter 苏擘 神经生物学研究所（6号楼 6620） bxs 103@sdu. edu. cn 0531 -88382329

Synapse and Synaptic Transmission

Neurons Introduction Structure & Function n Golgi Staining n Camillo Golgi n Reticular n theory Ramón y Cajal n Cell theory 3

Neurons Structure & Function n Cell Body (Soma): Life Support n Protein Synthesis n Single Nucleus n Axon: Longest process transmits messages away from cell body n Dendrites: Multiple processes off cell body – receive messages

Neurons http: //www. wisegeek. com/what-is-the-function-of-a-motor-

Pyramidal neuron visualized by green fluorescent protein Pyramidal neurons in the cerebral cortex Dense hippocampal CA 1 area pyramidal neurons and their downwardpointing apical dendrites labeled with yellow fluorescent protein.

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Campenot chamber Microfluidic chamber 9

The compartmentalized microfluidic chamber is used to isolate pure axonal m. RNA from mammalian cortical neurons. J. Neurosci, 2009 11

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Differences between Axons and Dendrites Axons Dendrites Take information away from the cell body Take information to the cell body Smooth surface Rough 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

Important Features of Neurons n EXCITABLE Membrane: Able to regulate the movement of ions (charges) across and along membrane---SIGNAL TRANSDUCTION

Action Potential

Outline n Types of synapses n Signal transmission at chemical synapses n Principles of synaptic integration 18

Synapse: a specialized junction that transfers nerve impulse information between neurons or neuron and effector cells. 19

Types of Synapses n n Electrical synapses n Occur at specialized sites called gap junction n Common in non-neural cells (astrocytes) and early embryonic stages Chemical synapses n Predominates in the mature human nervous system 20

Axodendritic synapse Axosomatic synapse Axoaxonic synapse 21

Gray’s Type I n n Excitatory synapses: permeable to Na+ and K+ (N -Ach. R) Gray’s type I: n Round synaptic vesicles n Large active zone (12 um 2) n Wide synaptic cleft (30 nm) n Extensive postsynaptic dense regions 22

Gray’s Type II n n Inhibitory synapses: permeable to Cl(GABA, Glycine) Gray’s type II: n Flattened synaptic vesicles n Small active zone (<1 um 2) n Narrow synaptic cleft (20 nm) n Intensive postsynaptic dense regions 23

Two categories of CNS synaptic membrane differentiations n Type I synapses typically contact specialized projections on the dendrites spines, less commonly contact the shafts of dendrites. n Type II synapses often contact the cell body. 24

Electrical Synapse n Gap junction – Adjacent cells electrically coupled through a channel. n Ionic current n Cytoplasm continuous n No synaptic cleft - 3. 5 nm n Brief delay n Bidirectional 25

Gap junctions n n Channels: n Connexon n Diameter is 2 nm 6 subunits: connexin 26

Rapid Transmission of Signal at Electrical Synapses An action potential in the presynaptic neuron causes the postsynaptic neuron to be depolarized within a fraction of a millisecond. 27

n escape mechanisms and other processes that require quick responses. 28

The chemical synapse is a specialized junction that transfers nerve impulse information from a presynaptic membrane to a postsynaptic membrane using neurotransmitters. Axodendritic synapse Axosomatic synanpse Axoaxonic synapse 29

Chemical Synapses n Presynaptic element n Synaptic vesicles n Active zone n Synaptic cleft n Postsynaptic density 30

Chemical Synapses n Neurotranmitters n 20 -50 nm cleft n Syanptic delay: 1 -5 ms or longer n unidirectional 31

Chemical synapses as seen with electron microscope 32

Presynaptic marker： Synaptophysin Postsynaptic marker： PSD-95 SV 2 34

Distinguishing Properties of Electrical and Chemical Synapses Electrical Synapse Chemical Synapse Distance between pre- and postsynaptic cell membranes 3. 5 nm 20 -50 nm Cytoplasmic continuity Yes No Ultrastructural components Gap-iunction channels Presynaptic vesicles and active zones; postsynaptic receptors Agent of transmission Ion current Chemical transmitter Synaptic delay Virtually absent Significant: at least 0. 3 ms, between pre- and postsynaptic cells usually 1 - 5 ms or longer Direction of transmission Usually bidirectional unidirectional 35

Outline n Types of synapses n Signal transmission at chemical synapses n Principles of synaptic integration 36

Signal transmission at chemical synapses From a presynaptic membrane to a postsynaptic membrane using neurotransmitters 37

Signal Transmission at Chemical Synapses n Neurotransmitters n NT Receptors n EPSP and IPSP 38

Neurotransmitters n Precursor transport n Synthesis n Storage n Release n Activation n Termination diffusion, degradation, uptake, autoreceptors 39

Presynaptic Axon Terminal Button Postsynaptic Membrane Dendritic Spine 40

(1) Precursor Transport 41

(2) Synthesis _ _ _ enzymes/cofactors NT 42

(3) Storage in vesicles 43

NT Terminal Button Dendritic Spine Synapse Vesicles 44

(4) Release Terminal Button Dendritic Spine Synapse Receptors 45

Terminal Button AP Dendritic Spine Synapse 46

Exocytosis 2+ Ca 47

(5) Activation 48

(6) Termination 49

(6. 1) Termination by. . . Diffusion 50

(6. 2) Termination by. . . Enzymatic degradation 51

(6. 3) Termination by. . . Reuptake 52

(6. 4) Termination by. . . Autoreceptors A 53

Principles of Chemical Synaptic Transmission n Basic Steps n Neurotransmitter synthesis Load neurotransmitter into synaptic vesicles Vesicles fuse to presynaptic terminal n Neurotransmitter spills into synaptic cleft n Binds to postsynaptic receptors Biochemical/Electrical response elicited in postsynaptic cell Removal of neurotransmitter from synaptic cleft n n

Critical role of calcium in vesicle fusion influx of Ca++ is both necessary and sufficient for vesicle fusion and neurotransmitter release 55

NT Receptors n Transmitter-gated ion channels n G-protein-coupled receptors n Autoreceptor 56

Transmitter-gated ion channels 57

G-protein-coupled receptors (GPCR) 58

Autoreceptor n In the membrane of the presynaptic terminal n G-protein-coupled receptors n Regulates NT release and synthesis A 59

Events from neurotransmitter release to postsynaptic excitation or inhibition 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-tomoment control of action potential generation. 60

Excitatory Postsynaptic Potential (EPSP) n An AP arriving in the presynaptic terminal cause the release of neurotransmitter n The molecules bind active receptor on the postsynaptic membrane 61

Excitatory Postsynaptic Potential (EPSP) n Opening transmittergated ions channels ( Na+) in postsynapticmembrane n Both an electrical and a concentration gradient driving Na+ into the cell; n The postsynaptic membrane will become depolarized (EPSP). 62

Inhibitory Postsynaptic Potential (IPSP) n A impulse arriving in the presynaptic terminal causes the release of neurotransmitter; n The molecular bind active receptors on the postsynaptic membrane, open CI- or, sometimes K+ channels; n More CI- enters, K+ outer the cell, producing a hyperpolarization in the postsynaptic membrane. 63

EPSPs & IPSPs’ differentiations EPSP IPSP Excitatory Inhibitory Depolarization Hyperpolarization Na+ influx K+ efflux or Cl- influx more likely to fire less likely to fire 64

Outline n Types of synapses n Signal transmission at chemical synapses n Principles of synaptic integration 65

SST/SOM PV+ interneuron n. NOS VIP CCK PV SST+ interneuron LPN Neuron 71, 995– 1013, September 22, 2011

Principles of Synaptic Integration n Most CNS neurons receive thousands of syanptic inputs that active different combinations of transmitter-gated ion channels and GPCRs. n The postsynaptic neuron integrates all of these signals and give rise to a simple form of output: action potentials. 67

EPSP Summation n Spatial summation n Temporal summation 68

Spatial summation n The adding together of EPSPs generated simultaneously at many different synapses on a dendrite. n Two or more presynaptic inputs are active at the same time A space (spatial) dependent process. Occurs in a Convergent Synapse n n 69

Temporal summation n The adding together of EPSPs generated at the same synapse if they occur in rapid succession, within 1 -15 msec of one another. n The same presynaptic fiber fires AP in quick succession n A Time (Temporal) dependent process n Occurs in a Divergent Synapse 70

Summation of postsynaptic potentials EPSPs & IPSPs summate n CANCEL EACH OTHER 71

n Synaptic Inhibition n Synaptic Facilitation 72

Synaptic Inhibition n Presynaptic inhibition n n Postsynaptic neuron produce decreased EPSP Postsynaptic inhibition n Postsynaptic neuron produce IPSP 73

Presynaptic inhibition n n The inhibition occurs at the presynaptic terminals before the signal ever reaches the synapse C and A form an axon-axon synapse (presynaptic synapse). Neuron C has no direct effect on neuron B, but it exert a presynaptic effect to decrease the amount of neurotransmitter released from A. C A B 74

Presynaptic Inhibition Excitatory Synapse A + B • A active • B more likely to fire • Add a 3 rd neuron ~ 75

Presynaptic Inhibition Excitatory Synapse A - + B C • Axon-axon synapse • C is inhibitory ~ 76

Presynaptic Inhibition Excitatory Synapse A - + B C • • • C active less NT from A when active B less likely to fire ~ 77

Postsynaptic inhibition n Effect of inhibitory synapses on the postsynaptic membrane n n Inhibitory interneuron release inhibitory transmitters and the postsynaptic neuron produce IPSP Afferent collateral inhibition 传入侧枝性抑制 (reciprocal inhibition) n Recurrent inhibition 回返性抑制 78

Reciprocal inhibition n Afferent fibers excites the motor neurons to extensor muscle. And its branches excite an interneuron, which secrete the inhibitory transmitter at synapses on the motor neurons to flexor muscle (IPSP) 79

Synaptic Facilitation n Presynaptic facilitation n Postsynaptic facilitation 80

Presynaptic facilitation n The structure is similar to presynaptic inhibition. But the effect is increase the amount of NTs released from A. C A facilitation B 81

Presynaptic facilitation Excitatory Synapse A + B • A active • B more likely to fire ~ 82

Presynaptic facilitation Excitatory Synapse A + C + B • C active (excitatory) • more NT from A when active (Mechanism: AP of A is prolonged and Ca 2+ channels are open for a longer period. ) • B more likely to fire ~ 83

Postsynaptic facilitation n EPSP summation n Postsynaptic neuron that has been partially depolarized is more likely to undergo AP. 84

Synaptic Plasticity n synaptic plasticity is the ability of the synapse between two neurons to change in strength in response to either use or disuse of transmission over synaptic pathways. n Long-term potentiation (LTP) Long-term depression (LTD) n LTP, LTD 为海马学习与记忆的分子基础。 n 85

Emphases n Characters of Chemical synapse and Electrical synapse n Structure of Chemical synapse n EPSP and IPSP 86

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