1. University of Jordan1 Physiology of Synapses in the CNS- L2-L4 Faisal I. Mohammed, MD, PhD

2. University of Jordan 2 Objectives Students should be able to:  Define synapse and list the types of synapse  Describe the mechanism of neurotransmitter release  List the major types of neurotransmitters (NT)  Compare the small molecules NT and Neuropeptides  Describe the resting membrane potential and Nernst Equation  Determine the how EPSP, IPSP and Presynaptic inhibition develops  Describe summation of EPSP and IPSP  Describe the characteristics of synapse (Fatigue and Delay)

3. University of Jordan 3 The Synapse  Structures important to the function of the synapse:  presynaptic vesicles: contain neurotransmitter substances to excite or inhibit postsynaptic neuron  mitochondria: provide energy to synthesize neurotransmitter  Membrane depolarization by an action potential causes emptying of a small number of vesicles into the synaptic cleft which excites or inhibits the postsynaptic neuron.

4. University of Jordan 4 Signal Transmission at the Synapse  2 Types of synapses  Electrical  ionic current spreads to next cell through gap junctions  faster, two-way transmission & capable of synchronizing groups of neurons  Chemical  one-way information transfer from a presynaptic neuron to a postsynaptic neuron  axodendritic -- from axon to dendrite  axosomatic -- from axon to cell body  axoaxonic -- from axon to axon

5. University of Jordan 5 Electrical Synapse

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7. 7 Neuronal Synapse and Transmitter release Chemical synapse

8. University of Jordan 8 Mechanism of Neurotransmitter Release  Presynaptic membranes contain voltage - gated calcium channels.  depolarization of the presynaptic membrane by an action potential opens voltage-gated Ca 2+ channels  influx of Ca 2+ induces the release of the neurotransmitter substance  the exact mechanism is unknown but it results in the fusion of the synaptic vessel to the membrane and release of transmitter by exocytosis

9. University of Jordan 9 Signal transmission at a chemical synapse

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11. University of Jordan 11 Action of Neurotransmitter on Postsynaptic Neuron  Postsynaptic membrane contains receptor proteins for the transmitter released from the presynaptic terminal.  These receptors contain a binding component and an ionophore component.  The binding component binds to the transmitter.  The ionophore component either opens an ion channel or activates a second messenger system.

12. University of Jordan 12 Ion Channels  Cation channels most often allow sodium ions to pass (some allow potassium or calcium).  Anion channels allow chloride to pass.  Transmitters that open sodium channels excite the postsynaptic neuron.  Transmitters that open chloride channels inhibit the postsynaptic neuron.  These channels open and close rapidly providing a means for rapid activation or rapid inhibition of postsynaptic neurons.

13. University of Jordan 13 Second Messenger Activators (SMAs)  Cause prolonged changes in the activity of neurons (seconds to months)  some processes like memory require long term changes in neuronal activity and function  About 75% of the SMAs are transduced with G- protein coupled receptors  G-protein activation initiates a cascade of events that leads to an increase in cAMP which causes protein phosphorylation which leads to alterations in the cellular activity.

14. University of Jordan 14 Neurotransmitter “Second Messenger” System

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17. University of Jordan 17 Neurotransmitters  Chemical substances that function as synaptic transmitters 1. Small molecules which act as rapidly acting transmitters  acetylcholine, norepinephrine, dopamine, serotonin, GABA, glycine, glutamate, NO 2. Neuropeptides  more potent than small molecule transmitters, cause more prolonged actions  endorphins, enkephalins, VIP, ect.  hypothalamic releasing hormones  TRH, LHRH, ect.  pituitary peptides  ACTH, prolactin, vasopressin, ect.

18. University of Jordan 18 Neurotransmitters

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