science of synaptic
TRANSCRIPT
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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
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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Electrical Synapses
Gap junction
Channel
Connexon- formed by six connexins
Cells are said to be electrically coupled
Flow of ions from cytoplasm to cytoplasm
Types of Synapses
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INSERT FIG. 5.1 (Yes, deliberately out of order)
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Types of Synapses
Electrical Synapses (Contd)
Very fast transmission
Postsynaptic potentials (PSPs)
Synaptic integration: Several PSPs occurringsimultaneously to excite a neuron (i.e. causes AP)
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Types of Synapses
Chemical Synapses
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Types of Synapses
Chemical Synapses
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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)
Grays Type I: Asymmetrical, excitatory
Grays Type II: Symmetrical, inhibitory
Types of Synapses
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The Neuromuscular Junction
(NMJ) Studies of NMJ established
principles of synaptictransmission
Types of Synapses
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Principles of Chemical SynapticTransmission
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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Neurotransmitters
Amino acids: Small organic molecules
e.g., Glutamate, Glycine, GABA
Amines: Small organic molecules
e.g., Dopamine, Acetylcholine, Histamine
Peptides: Short amino acid chains (i.e. proteins)stored in and released from secretory granules
e.g., Dynorphin, Enkephalins
Principles of Chemical SynapticTransmission
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Neurotransmitters
Principles of Chemical SynapticTransmission
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Neurotransmitter Synthesis and Storage
Amines, amino acids, peptides
Principles of Chemical SynapticTransmission
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Neurotransmitter Release
Exocytosis: Process by which vesicles release theircontents
Principles of Chemical SynapticTransmission
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Neurotransmitter Release (Contd)
Mechanisms
Process of exocytosis stimulated by release ofintracellular calcium, [Ca2+]i
Proteins alter conformation - activated
Vesicle membrane incorporated into presynapticmembrane
Neurotransmitter released
Vesicle membrane recovered by endocytosis
Principles of Chemical SynapticTransmission
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Neurotransmitter receptors:
Ionotropic: Transmitter-gated ion channels
Principles of Chemical SynapticTransmission
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Metabotropic: G-protein-coupled receptor
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Excitatory and Inhibitory Postsynaptic Potentials:
EPSP:Transient postsynaptic membrane depolarization bypresynaptic release of neurotransmitter
IPSP: Transient hyperpolarization of postsynaptic membranepotential caused by presynaptic release of neurotransmitter
Reversal potential concept
Principles of Chemical SynapticTransmission
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Neurotransmitter Recovery and Degradation
Diffusion: Away from the synapse
Reuptake: Neurotransmitter re-enters presynapticaxon terminal
Enzymatic destruction inside terminal cytosol orsynaptic cleft
Desensitization: e.g., AChE cleaves Ach to inactivestate
Principles of Chemical SynapticTransmission
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Neuropharmacology
Effect of drugs on nervous system tissue
Receptor antagonists: Inhibitors of neurotransmitterreceptors
Curare
Receptor agonists: Mimic actions of naturallyoccurring neurotransmitters
Nicotine
Defective neurotransmission: Root cause ofneurological and psychiatric disorders
Principles of Chemical SynapticTransmission
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Principles of Synaptic Integration Synaptic Integration
Process by which multiple synaptic potentialscombine within one postsynaptic neuron
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Quantal Analysis of EPSPs
Synaptic vesicles: Elementary units of synaptic
transmission 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 amillivolt
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EPSP Summation
Allows for neurons to perform sophisticatedcomputations
Integration: EPSPs added together to producesignificant postsynaptic depolarization
Spatial: EPSP generated simultaneously in differentspaces
Temporal: EPSP generated at same synapse in rapidsuccession
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The Contribution of Dendritic Properties to SynapticIntegration
Dendrite as a straight cable Membrane depolarization falls off exponentially with
increasing distance
Vx = Vo/ex/
Dendritic length constant ()
In reality, dendrites are very elaborate structuresthat contribute to more complex integrativeproperties
Principles of Synaptic Integration
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The Contribution ofDendritic Properties to
Synaptic Integration
Principles of Synaptic Integration
Vx=V
o* e-x/
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Excitable Dendrites
Dendrites of neurons: voltage-gated sodium,
calcium, and potassium channels
Can act as amplifiers (vs. passive)
Dendritic sodium channels: May carry electricalsignals in opposite direction, from soma outwardalong dendrites
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Inhibition
Action of synapses to take membrane potential away
from action potential threshold
Exerts powerful control over neuron output
Principles of Synaptic Integration
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IPSPs and Shunting Inhibition
Excitatory vs. inhibitory synapses: Bind different
neurotransmitters, allow different ions to pass throughchannels
Membrane potential more negative than -65mV =hyperpolarizing IPSP
Shunting Inhibition: Inhibiting current flow from soma toaxon hillock
Principles of Synaptic Integration
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Shunting Inhibition: Inhibiting current flow from soma toaxon hillock
Principles ofSynaptic Integration
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The Geometry of Excitatory and Inhibitory Synapses
Excitatory synapses
Grays type I morphology
Spines: Excitatory synapses
Inhibitory synapses
Grays type II morphology
Clustered on soma and near axon hillock
Principles of Synaptic Integration
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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 manyneurological and psychiatric disorders
Key to understanding the neural basis of learningand memory
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End of Presentation
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Principles of Synaptic Integration
Modulation
Synaptic transmission thatmodifies effectiveness ofEPSPs generated by othersynapses with transmitter-gated ion channels
Example: Activating NE receptor