QUIZ/TEST REVIEW NOTES SECTION 7 NEUROPHYSIOLOGY [THE SYNAPSE AND PHARMACOLOGY] Learning Objectives: Explain how neurons communicate stimulus intensity Explain how action potentials are conducted along the axon Describe the significance of myelination 1. THE SYNAPSE a. Defined - Region where an axon terminal meets its target cell - Number of synapses is not fixed - Single neuron can have up to 10,000 synapses b. Components of a synapse 1. Presynaptic Neuron - The neuron that delivers the signal to the synapse - Contains many small synaptic vesicles and large mitochondria 2. Synaptic Cleft - Space between pre/pos synaptic neuron where neurotransmitters are found E.C.F. 3. Postsynaptic Cell - Cell that receives signals from the Presynaptic neuron - May be neurons or non-neuronal cells c. Electrical Synapse 1. Definition - Pass an electrical signal or current directly from cytoplasm of one cell to another through gap junctions - Occur mainly in CNS neurons 2. Functionality - Found in glial cells, cardiac muscle, smooth muscle - Advantage: Rapid conduction of signals from cell to cell that synchronizes activity within network of cells d. Chemical Synapse 1. Definition - Use neurotransmitters to carry information from one cell to the next - Electrical signal of presynaptic cell is converted into chemical signal that crosses synaptic cleft between presynaptic neuron and target - Chemical neurotransmitter transmission either initiates an electrical response or actives a second messenger pathway 1
2. SYNAPTIC TRANSMISSION a. Arrival of the action potential - When depolarization of action potential reach axon terminal, the change in membrane potential sets off sequence of events - Axon terminal membrane has voltage-gated Ca2+ channels that open in response to depolarization - Calcium ions more concentrated in E.C.F. than in the cytosol and move into the cell b. Exocytosis of Neurotransmitter - The binding of Ca2+ to regulatory proteins in the I.C.F. initiates exocytosis - Membrane of the synaptic vesicle fuses with cell membrane with aid of multiple membrane proteins - Fused area opens and NT inside synaptic vesicle are released into synaptic cleft Kiss-and-Run Pathway > Synaptic vesicles fuse to presynaptic membrane at complex called the fusion pore > Fusion opens small channel that is just large enough for NT to pass > Instead of vesicle now fusing with cell membrane it backs off and returns to I.C.F. cytoplasm c. Post-synaptic response - NT molecules diffuse across synaptic cleft to bind with membrane receptors on postsynaptic cell, which will initiate a postsynaptic cell response - Chemical neurotransmitter transmission either initiates an electrical response or actives a second messenger pathway d. Multiple Receptors on Post Synaptic Neuron 1. Definition - All neurotransmitters have one or more receptors types to bind except nitric oxide 2. Receptor subtypes - Receptors subtypes allows one neurotransmitter to have different effects in different tissues - Subtypes distinguished by combinations of letter and number subscripts 2
3 3. N.T. Receptor Categories - Ligand Gated Ion Channels: Simplest chemical receptor gate that opens/closes thus altering ion concentrations [Ionotropic receptors: alter ion channel function] [Linked to fast synaptic potentials] - G Protein-Coupled Receptors (GPCR): Linked to second messenger systems [Metabotropic receptors: Exert actions through second messenger system/some open or close ion channels] [Linked to slow synaptic potentials]
4. Basic Receptor Groups (a) Cholinergic Receptors [mainly ACh NT receptors] Nicotinic - Agonist - Locations: CNS, skeletal muscle, autonomic division PNS, - Monovalent cation channels through which Na+ and K+ pass - Na+ concentration different exceeds K+ so more Na enters then K exiting leading to depolarization of postsynaptic cell Muscarinic - Agonist - Coupled to G proteins and linked to second messenger systems - Locations: CNS, autonomic parasympathetic PNS (b) Adrenergic Receptors - Linked to G proteins and initiate second messenger cascades - Two subclasses alpha and beta (c) Glutaminergic Receptors - Main excitatory neurotransmitter in CNS - Acts as a neuromodulator For picture diagram go to page 5 Long Term Potentiation - AMPA Receptor Ligand-gated monovalent cation channels that opens when Glutamate binds and cell depolarizes due to net Na+ influx - NMDA Receptors Cation channels that allow Na+, K+, and Ca2+ to pass; channel opening requires both glutamate binding and change in membrane potential; NMDA receptor channel is blocked by magnesium ion at resting membrane potential; Glutamate binding: opens ligand-activated gate Cell depolarization: Mg2+ blocking channel expelled 4
e. Sensitization of long-term potentiation a. Definition Sensitization [facilitation] - Simulation of postsynaptic cell can increase sensitivity of the cell to future stimuli - Glutamate release and calcium influx result in facilitated cell or longterm potentiation a. Definition Long-Term Potentiation - With long-term potentiation the Presynaptic cell increases its glutamate release and the postsynaptic cell becomes more sensitive to glutamate - Activity at a synapse induces sustained changes in the quality or quantity of synaptic connections b. Effect of - Believed to be related to the neural processes of learning and memory c. Mechanism - Presynaptic neurons releases Glutamate, and the chemical binds to both AMPA and NMDA receptors - AMPA activation receptor opens cation channel allowing influx Na+ - Cell becomes depolarized from Na+ that releases an electrical charge repulsing Mg2+ out of NMDA receptor, opening up the channel allowing Ca2+ to enter - Ca2+ initiates second messenger pathway and sends paracrine to presynaptic cell to enhance NT release - This all leads to postsynaptic cell becoming more sensitive to glutamate possibly by inserting more glutamate receptors in the postsynaptic membrane 3. TERMINATION OF SYNAPTIC ACTIVITY 1. Calcium removal from axon terminus - Without calcium no depolarization effect takes place and no movement on neurotransmitter vesicles towards cellular membrane 2. Neurotransmitter removal from cleft 5
6 a. Glial Cells - Neuron helper cells b. Reuptake - Proteins found on presynaptic neuron that reuptake pump N.T. back into I.C.F. c. Degradation - Enzymes inactivate Neurotransmitters in synaptic cleft/e.c.f.