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Description : Check out this medical presentation on Neurology, which is titled "Synaptic Transmission", to know about Synaptic Transmission.

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Published on : Aug 23, 2021 | Views : 2117 | Downloads : 4

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Slide 1-

Neuroscience: Exploring the Brain, 3e Chapter 5: Synaptic Transmission
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Introduction Synaptic Transmission Information transfer at a synapse Plays role in all the operations of the nervous system 1897: Charles Sherrington- “synapse” Cajal vs Golgi (1906) Chemical and electrical synapses 1921- Otto Loewi 1959- Furshpan and Potter
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Types of Synapses Direction of Information Flow In one direction: Neuron to target cell First neuron = Presynaptic neuron Target cell = Postsynaptic neuron
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Type of Synapses Golgi – Continuous synapse Cajal – Contiguous synapse
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Gap junction Channel Connexon- formed by six connexins Cells are said to be “electrically coupled” Flow of ions from cytoplasm to cytoplasm Electrical Synapse
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INSERT FIG. 5.1 (Yes, deliberately out of order)
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Electrical Synapse Very fast transmission Postsynaptic potentials (PSPs) Synaptic integration: Several PSPs occurring simultaneously to excite a neuron (i.e. causes AP)
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Chemical Synapse
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Chemical Synapse
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CNS Synapses (Examples) Axodendritic: Axon to dendrite Axosomatic: Axon to cell body Axoaxonic: Axon to axon Dendrodendritic: Dendrite to dendrite Types of Synapses
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CNS Synapses (Examples) Gray’s Type I: Asymmetrical, excitatory Gray’s Type II: Symmetrical, inhibitory Types of Synapses
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The Neuromuscular Junction (NMJ) Studies of NMJ established principles of synaptic transmission Types of Synapses
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An Actual Neuromuscular Synapse Goodsell, D. S. (2009), Neuromuscular synapse. Biochem. Mol. Biol. Educ., 37: 204–210. doi: 10.1002/bmb.20297
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Principles of Chemical Synaptic Transmission Basic Steps Neurotransmitter synthesis Load neurotransmitter into synaptic vesicles Depolarization  Vesicles fuse to presynaptic terminal Neurotransmitter spills into synaptic cleft Binds to postsynaptic receptors Biochemical/Electrical response elicited in postsynaptic cell Removal of neurotransmitter from synaptic cleft
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Synaptic Transmission at Neuromuscular Junction
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Principles of Chemical Synaptic Transmission Basic Steps Neurotransmitter synthesis Load neurotransmitter into synaptic vesicles Depolarization  Vesicles fuse to presynaptic terminal Neurotransmitter spills into synaptic cleft Binds to postsynaptic receptors Biochemical/Electrical response elicited in postsynaptic cell Removal of neurotransmitter from synaptic cleft
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Amino acids: Small organic molecules Neurotransmitters
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Amino acids: Small organic molecules Amines: Small organic molecules Neurotransmitters
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Amino acids: Small organic molecules Amines: Small organic molecules Peptides: Short amino acid chains (i.e. proteins) stored in and released from secretory granules Neurotransmitters
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____ ____: Small organic molecules e.g., Glutamate, Glycine, GABA ____ : Small organic molecules e.g., Dopamine, Acetylcholine, Histamine ____ : Short amino acid chains (i.e. proteins) stored in and released from secretory granules e.g., Dynorphin, Enkephalins Neurotransmitters
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Neurotransmitter Synthesis and Storage Loading Neurotransmitters
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Dense Core Vesicles Goodsell, D. S. (2009), Neuromuscular synapse. Biochem. Mol. Biol. Educ., 37: 204–210. doi: 10.1002/bmb.20297
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Exocytosis: Process by which vesicles release their contents Neurotransmitter Release
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Process of exocytosis stimulated by release of intracellular calcium, [Ca2+]i Proteins alter conformation - activated Vesicle membrane incorporated into presynaptic membrane Neurotransmitter released Vesicle membrane recovered by endocytosis Mechanism of Neurotransmitter release (Clathrin-mediated endocytosis: http://biochem.web.utah.edu/iwasa/projects/clathrin.html)
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- Ionotropic: Transmitter-gated ion channels Neurotransmitter Receptors and Post-synaptic Response
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Metabotropic: G-protein-coupled receptor Neurotransmitter Receptors and Post-synaptic Response
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EPSP:Transient postsynaptic membrane depolarization by presynaptic release of neurotransmitter IPSP: Transient hyperpolarization of postsynaptic membrane potential caused by presynaptic release of neurotransmitter Reversal potential Excitatory and Inhibitory Postsynaptic Potentials
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Diffusion: Away from the synapse Reuptake: Neurotransmitter re-enters presynaptic axon terminal Enzymatic destruction inside terminal cytosol or synaptic cleft Desensitization: despite continued presence of ACh, transmitter-gated channels close Neurotransmitter Recovery and Degradation
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Effect of drugs on nervous system tissue Receptor antagonists: Inhibitors of neurotransmitter receptors Curare Receptor agonists: Mimic actions of naturally occurring neurotransmitters Nicotine Defective neurotransmission: Root cause of neurological and psychiatric disorders Neuropharmacology
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Principles of Synaptic Integration Process by which multiple synaptic potentials combine within one postsynaptic neuron
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Synaptic vesicles: Elementary units of synaptic transmission. Almost fixed amount of nerotransmitter Quantum: An indivisible unit Miniature postsynaptic potential (“mini”) Quantal analysis: Used to determine number of vesicles that release during neurotransmission Neuromuscular junction: About 200 synaptic vesicles, EPSP of 40mV or more CNS synapse: Single vesicle, EPSP of few tenths of a millivolt Quantal Analysis of EPSPs
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Allows for neurons to perform sophisticated computations EPSP summation: EPSPs added together to produce significant postsynaptic depolarization Spatial: EPSP generated simultaneously in different spaces Temporal: EPSP generated at same synapse in rapid succession Synaptic Integration - EPSP Summation
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Synaptic Integration - EPSP Summation
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Assume: Dendrite as a straight cable (~spinal motor dendrite) Membrane depolarization falls off exponentially with increasing distance Vx = Vo/ex/  Dendritic length constant (): at which, 37% of Vo In reality, dendrites are very elaborate structures that contribute to more complex integrative properties The Contribution of Dendritic Properties to Synaptic Integration
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Vx=Vo * e-x/λ The Contribution of Dendritic Properties to Synaptic Integration
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Dendrites of neurons: voltage-gated sodium, calcium, and potassium channels Can act as amplifiers (vs. passive) Dendritic sodium channels: May carry electrical signals in opposite direction, from soma outward along dendrites (Cajal?) Excitable Dendrites
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Action of synapses to take membrane potential away from action potential threshold Exerts powerful control over neuron output Inhibition
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Excitatory vs. inhibitory synapses: Bind different neurotransmitters, allow different ions to pass through channels IPSPs and Shunting Inhibition
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Excitatory vs. inhibitory synapses: Bind different neurotransmitters, allow different ions to pass through channels Membrane potential more negative: hyperpolarizing IPSP ECl = -65 mV ? Shunting Inhibition: Inhibiting current flow from soma to axon hillock IPSPs and Shunting Inhibition
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Shunting Inhibition
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Excitatory synapses Gray’s type I morphology Spines: Excitatory synapses Inhibitory synapses Gray’s type II morphology Clustered on soma and near axon hillock The Geometry of Excitatory and Inhibitory Synapses
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Concluding Remarks Chemical synaptic transmission Rich diversity allows for complex behavior Provides explanations for drug effects Defective transmission is the basis for many neurological and psychiatric disorders Key to understanding the neural basis of learning and memory
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Question of the Day How stepping on a rusty nail may result in muscle spasms and even eventual death? Hint: It involves synaptic transmission. In general, what molecular/cellular events happened? Are there effective treatments? Does the behavior a result of (mostly) defects in inhibitory or excitatory synapse? How do these defects affect synaptic integration?
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Principles of Synaptic Integration Modulation Synaptic transmission that modifies effectiveness of EPSPs generated by other synapses with transmitter-gated ion channels Example: Activating NE β receptor