The Synapse

1. The Synapse • A junction that mediates information transfer from one neuron: • To another neuron, or • To an effector cell (muscle, secretory…) • Presynaptic neuron—conducts impulses toward the synapse (sending side) • Postsynaptic neuron—transmits impulses away from the synapse (receiving side)

2. Types of Synapses • Axodendritic—axon of one to dendrite of another • Axosomatic—axon of one to soma of another • Less common types: • Axoaxonic (axon to axon) • Dendrodendritic (dendrite to dendrite) • Dendrosomatic (dendrite to soma)

3. Axodendritic synapses Dendrites Axosomatic synapses Cell body Axoaxonic synapses (a) Axon Axon Axosomatic synapses Cell body (soma) of postsynaptic neuron (b) Figure 11.16

4. Electrical Synapses • Less common than chemical synapses • Neurons are electrically coupled (joined by gap junctions) • Communication is very rapid, and may be unidirectional or bidirectional • Are important in: • Embryonic nervous tissue • Some brain regions

5. Chemical Synapses • Specialized for the release and reception of neurotransmitters • Typically composed of two parts • Axon terminal of the presynaptic neuron, which contains synaptic vesicles • Receptor region on the postsynaptic neuron

6. Synaptic Cleft • Fluid-filled space between presynaptic and postsynaptic neurons, found at chemical synapses • Transmission across the synaptic cleft • Is a chemical event (not electrical) • Involves release, diffusion, and binding of neurotransmitters • Provides unidirectional communication between neurons

7. Synaptic Transmission Summary • Action potential arrives at presynaptic neuron’s axon terminal and opens voltage-gated calcium channels • Calcium enters neuron terminal and causes synaptic vesicle fusion with cell membrane • Neurotransmitter exocytosis occurs • Neurotransmitter diffuses across cleft and binds to receptors on postsynaptic neuron • Ion channels in membrane of post-synaptic cell open, causing excitation or inhibition (graded potential) • Neurotransmitter diffuses away from receptors as it is broken down in the cleft and/or taken back up by pre-synaptic neuron

8. Chemical synapsestransmit signals fromone neuron to anotherusing neurotransmitters. Presynapticneuron Presynapticneuron Postsynapticneuron 1 Action potentialarrives at axon terminal. 2 Voltage-gated Ca2+channels open and Ca2+enters the axon terminal. Mitochondrion Ca2+ Ca2+ Ca2+ Ca2+ Synapticcleft 3 Ca2+ entry causesneurotransmitter-containing synapticvesicles to release theircontents by exocytosis. Axonterminal Synapticvesicles 4 Neurotransmitterdiffuses across the synapticcleft and binds to specificreceptors on thepostsynaptic membrane. Postsynapticneuron Figure 11.17, step 4

9. Ion movement Graded potential 5 Binding of neurotransmitteropens ion channels, resulting ingraded potentials. Figure 11.17, step 5

10. Enzymaticdegradation Reuptake Diffusion awayfrom synapse 6 Neurotransmitter effects are terminatedby reuptake through transport proteins,enzymatic degradation, or diffusion awayfrom the synapse. Figure 11.17, step 6

11. Termination of Neurotransmitter Effects • Neurotransmitter effect is terminated in a few milliseconds by • Degradation by enzymes • Reuptake by astrocytes or axon terminal • Diffusion away from synaptic cleft

12. Synaptic Delay • Neurotransmitter must be released, diffuse across synapse, and bind to receptors • Synaptic delay = time needed to do this (0.3-5.0 ms) • Synaptic delay is the rate-limiting step of neural transmission (in short neurons at least)

13. Postsynaptic Potentials • Graded potentials • Strength determined by: • Amount of neurotransmitter released • Time the neurotransmitter is in the area • Types of postsynaptic potentials • EPSP—excitatory postsynaptic potentials • IPSP—inhibitory postsynaptic potentials

14. Table 11.2 (1 of 4)

15. Table 11.2 (2 of 4)

16. Table 11.2 (3 of 4)

17. Table 11.2 (4 of 4)

18. Excitatory Synapses and EPSPs • Neurotransmitter binds to and opens chemically gated channels that allow simultaneous flow of Na+ and K+ in opposite directions • Na+ influx is greater than K+ efflux, causing a net depolarization • EPSP helps trigger AP at axon hillock if EPSP is of threshold strength and opens the voltage-gated channels

19. An EPSP is a local depolarization of the postsynaptic membrane that brings the neuron closer to AP threshold. Neurotransmitter binding opens chemically gated ion channels, allowing the simultaneous pas- sage of Na+ and K+. Membrane potential (mV) Threshold Stimulus Time (ms) (a) Excitatory postsynaptic potential (EPSP) Figure 11.18a

20. Inhibitory Synapses and IPSPs • Neurotransmitter binds to and opens channels for K+ or Cl– • Causes hyperpolarization (inside of cell becomes more negative) • Reduces the postsynaptic neuron’s ability to produce an action potential

21. An IPSP is a local hyperpolarization of the postsynaptic membrane and drives the neuron away from AP threshold. Neurotransmitter binding opens K+ or Cl– channels. Membrane potential (mV) Threshold Stimulus Time (ms) (b) Inhibitory postsynaptic potential (IPSP) Figure 11.18b

22. Integration: Summation • One EPSP cannot induce an action potential • EPSPs can sum to reach threshold • IPSPs and EPSPs can cancel each other out

23. Integration: Summation • Temporal summation • One presynaptic neuron sends several or many impulses in a short time to the postsynaptic neuron • Spatial summation • Multiple presynaptic neurons stimulate the post-synaptic neuron simultaneously

24. E1 E1 Threshold of axon of postsynaptic neuron Resting potential E1 E1 E1 E1 Time Time (a) No summation: 2 stimuli separated in time cause EPSPs that do not add together. (b) Temporal summation: 2 excitatory stimuli close in time cause EPSPs that add together. Excitatory synapse 1 (E1) Excitatory synapse 2 (E2) Inhibitory synapse (I1) Figure 11.19a, b

25. E1 E1 E2 I1 E1 + E2 I1 E1 + I1 Time Time (c) Spatial summation: 2 simultaneous stimuli at different locations cause EPSPs that add together. (d) Spatial summation of EPSPs and IPSPs: Changes in membane potential can cancel each other out. Figure 11.19c, d

26. Neurotransmitters • Most neurons make two or more neurotransmitters, which are released at different stimulation frequencies • 50 or more neurotransmitters have been identified • Classified by chemical structure and by function

27. Chemical Classes of Neurotransmitters • Acetylcholine (Ach) • Released at neuromuscular junctions and some autonomic neurons • Synthesized in the pre-synaptic neuron • Degraded by acetylcholinesterase (AChE)

28. Chemical Classes of Neurotransmitters • Biogenic amines include: • Norepinephrine (NE) • Epinephrine • Serotonin • Many others • Broadly distributed in the brain • Play roles in emotional behaviors and the biological clock

29. Chemical Classes of Neurotransmitters • Amino acids include: • GABA—Gamma ()-aminobutyric acid • Glutamate • Many others

30. Functional Classification of Neurotransmitters • Excitatory (depolarizing) and/or inhibitory (hyperpol.) • Determined by receptor type on postsynaptic neuron • GABA usually inhibitory • Glutamate, epinephrine usually excitatory • Acetylcholine • Excitatory at neuromuscular junctions in skeletal muscle • Inhibitory in cardiac muscle

31. Neurotransmitter Actions • Direct action • Neurotransmitter binds to channel-linked receptor and opens ion channels • Promotes rapid responses • Examples: ACh; glutamate and GABA at some of their synapses

32. Neurotransmitter Actions • Indirect action • Neurotransmitter binds to a G protein-linked receptor and acts through an intracellular second messenger • Promotes long-lasting effects • Examples: Norepinephrine, epinephrine, serotonin; glutamate and GABA at some of their synapses