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Synaptic

transmission

Dr Reem Abraham

Learning Objectives

1. Apply the physiological implications of myelination to distinguish action potential propagation and saltatory conduction in myelinated vs unmyelinated axons.
2. Describe the synapse.
3. Apply the physiology of neurotransmitter release, including the implicated ion channels and enzymes, to the release and termination of cholinergic synaptic transmission.

At the end of this lecture, students should

be able to:

• (^) Synapses: the junction across which signals or action potentials are transmitted from a presynaptic to a postsynaptic structure (e.g., neurons, muscle).
• (^) Synapses allow nerve cells to communicate with one another
• (^) Synaptic transmission: the process of communication between two neurons, or between nerve and skeletal muscle (NMJ) involving the: - (^) a) release of a neurotransmitter by the presynaptic neuron - (^) b) neurotransmitter binding to receptors on the Synap se

• (^) The axon of the presynaptic neuron terminates on: ‒ (^) dendrites, soma, or axon of the postsynaptic neurons ‒ (^) muscle (neuro-muscular junction) ‒ (^) endocrine gland (neuro- endocrine) Synapse s 1 2 3

• (^) Two types of synapses: chemical and electrical
• (^) Chemical synapses
• (^) A type of synapse that transmits signals between excitable cells separated by the synaptic cleft via a chemical neurotransmitter
• (^) Eg: neuromuscular junction  (^) Synaptic transmission in CNS are mainly via chemical synapses
• (^) Electrical synapses
• (^) A type of synapse that transmits signals between excitable cells joined by gap junctions, by the flow of electrical current (i.e., movement of ions). Chemical and electrical synapses based on the mechanism of synaptic transmission

Chemical and Electrical Synapses

• (^) Receptors on postsynaptic neurons: ionotropic (ion- channel linked) or metabotropic (act via second messengers) Movement of ions through gap junctions

Neurotransmitters  (^) Criteria requirements that define a neurotransmitter

1. Synthesized and stored in synaptic vesicles at the presynaptic terminal (of the presynaptic neuron)
2. Released by depolarization: Ca 2+ influx into the presynaptic terminal
3. Binds to specific receptors on postsynaptic membrane

Neuromuscular junction (NMJ): a type of chemical synapse Neuromuscular transmission: synaptic transmission across a chemical synapse

Postsynaptic receptors: Ionotropic and metabotropic receptors

• (^) The action of a specific neurotransmitter depends on the type of receptors present on postsynaptic neuron Ionotropic receptors Metabotropic receptors

Ionotropic receptors: ligand- gated ion channels Metabotropic receptors (GPCRs) Nicotinic Acetylcholine (ACh) receptors Muscarinic Acetylcholine (ACh) receptors α and β receptors for norepinephrine and epinephrine Glutamate  Kainate, AMPA, NMDA Glutamate Glycine GABAA, GABAC GABAB

Metabotropic Receptors

• (^) G protein-coupled receptors (GPCRs)
• (^) Modulate synaptic transmission through the production of second messengers (i.e. Ca++, Camp, cGMP )
• (^) Do not have ion channels as part of their structure (indirectly gates the ion channels)
• (^) Can either be excitatory or inhibitory
• (^) Receptor tyrosine kinases (RTKs) ‒ (^) gate channels directly or indirectly by phosphorylation Review the lecture on signaling
• (^) Binding of GABA to GABA A and GABA C receptors increases Cl-influx into the postsynaptic neuron GABAB receptors are metabotropic, GPCRs

Action potential reaches the end of presynaptic nerve terminal It increases permeability of presynaptic nerve terminal endings to Ca 2+ Ca 2+ influx into the presynaptic nerve terminal through voltage gated Ca 2+ channels Mechanism of synaptic transmission in a chemical synapse Depolarization of presynaptic membrane Increased Ca2+ in the presynaptic terminal

Diffusion of neurotransmitter through the synaptic cleft & binding to postsynaptic membrane receptors (ionotropic or metabotropic) Changes in ion permeability of the postsynaptic membrane Binding of neurotransmitter to ionotropic receptors Binding of neurotransmitter to metabotropic receptors G proteins dissociate from the receptor and

1. interact directly with ion channels on postsynaptic membrane or
2. bind to other effector proteins, such as enzymes, that produce SECOND MESSENGERS that changes the ion permeability (either open or close ion channels) Development of postsynaptic potentials (EPSP/ IPSP) Generation of action potential if the summated postsynaptic potentials reach threshold

 (^) Termination of neurotransmitter action

• (^) reuptake
• (^) enzymatic degradation
• (^) diffusion away from synaptic cleft
• (^) Vesicles are recovered by Clathrin - mediated endocytosis, filled again & the cycle repeats