Synaptic Transmission and Information Flow

Synaptic Transmission Introduction

• Synaptic transmission involves information transfer at a synapse
• This process plays a role in all operations of the nervous system
• Charles Sherrington coined the term "synapse" in 1897
• Chemical and electrical synapses are the two main types
• Otto Loewi discovered vagustoff in 1921
• Eccles researched CNS chemical synapses in the 1950s
• Furshpan & Potter discovered electrical synapses

Direction of Information Flow

• Information generally flows in one direction: from neuron to target cell
• The first neuron in the sequence is the presynaptic neuron
• The target cell is the postsynaptic neuron
• The two main types of synapses are electrical and chemical

Electrical Synapses

• Gap junctions are key components of electrical synapses
• Channels within gap junctions allow direct communication between cells
• A connexon forms each channel and is composed of six connexins
• Electrical synapses allow cells to be "electrically coupled"
• Ions flow directly from the cytoplasm of one cell to another
• Electrical synapses are involved in motor control in the medulla

Gap Junctions

• Unlike most chemical synapses, gap junctions are bidirectional
• Gap junctions facilitate very fast transmission
• Postsynaptic potentials (PSPs) occur as a result of this transmission

Chemical Synapses

• Chemical synapses are the most common type of synapse

Components of Chemical Synapses

• Key components include the axon terminal (presynaptic element), synaptic cleft, and postsynaptic dendrite
• Other components include secretory granules, mitochondria, synaptic vesicles, receptors, and postsynaptic density

Types of CNS Synapses

• Axodendritic synapses connect an axon to a dendrite
• Axosomatic synapses connect an axon to a cell body
• Axoaxonic synapses connect an axon to another axon
• Axospinous synapses connect an axon to a dendritic spine
• Dendrodendritic synapses connect a dendrite to another dendrite

Sizes and shapes of CNS Synapses

• CNS synapses have a lot of variety
• Two categories of CNS synaptic membrane differentiations exists
• Gray's type I synapses are asymmetrical and usually excitatory
• Gray's type II synapses are symmetrical and usually inhibitory

Neuromuscular Junction (NMJ)

• Studies of the NMJ have established key principles of synaptic transmission
• NMJs are very reliable

Otto Loewi's Experiment

• Otto Loewi’s 1921 frog heart experiment demonstrated the role of the vagus nerve and acetylcholine in slowing heart rate
• Loewi's experiment provided proof that chemicals transmit impulses between nerve cells and target organs

Acetylcholine (ACh)

• Acetylcholine was the first neurotransmitter discovered, by Otto Loewi
• It is found at NMJs
• Black widow venom affects acetylcholine transmission
• Botulin and Botox also interfere with acetylcholine as well
• Nerve gasses & insecticides interfere with acetylcholine
• Alzheimer's Disease affects acetylcholine

Overview of Chemical Synaptic Transmission

• Process includes neurotransmitter synthesis
• Loading of neurotransmitter into synaptic vesicles
• Vesicle fusion to the presynaptic terminal
• Neurotransmitter spill into the synaptic cleft
• Binding to postsynaptic receptors
• Biochemical/electrical response elicited in the postsynaptic cell
• Removal of neurotransmitter from the synaptic cleft

Neurotransmitter Categories

• Amino acids are small organic molecules stored in vesicles, examples include glutamate, glycine, and GABA
• Amines are small organic molecules stored in vesicles, examples include dopamine, acetylcholine, and histamine
• Peptides are short amino acid chains (proteins) stored in secretory granules/dense core vesicles, examples include CCK and enkephalins

Neurotransmitter Synthesis and Storage

• Neurotransmitters are synthesized and either stored in vesicles or granules

Mechanisms of Neurotransmitter Release

• The process begin with a loaded vesicle
• Exocytosis is stimulated by intracellular calcium [Ca²⁺]
• Proteins alter conformation
• The SNARE family is activated
• Vesicle membrane becomes incorporated into the presynaptic membrane
• Neurotransmitter is released into the synaptic cleft
• Vesicle membrane is then recovered by endocytosis

Postsynaptic Potentials

• EPSP is a transient postsynaptic membrane depolarization caused by presynaptic release of neurotransmitter
• IPSP is transient hyperpolarization of postsynaptic membrane potential caused by presynaptic release of neurotransmitter

Neurotransmitter Receptors

• Transmitter-gated ion channels (ligand-gated or ionotropic)
• G-protein-coupled receptors (metabotropic)

Autoreceptors

• Autoreceptors are commonly found in the membrane of the presynaptic axon terminal
• Presynaptic receptors are sensitive to the neurotransmitter released by the presynaptic terminal
• Autoreceptors commonly inhibit neurotransmitter release
• It acts as a safety valve

Neurotransmitter Recovery and Degradation

• Diffusion of transmitter molecules away from the synapse occurs
• Reuptake occurs when neurotransmitter re-enters the presynaptic axon terminal
• Enzymatic destruction occurs inside the terminal cytosol or synaptic cleft
• Glial cells are involved in some cases

Neuropharmacology

• Neuropharmacology involves study of effects of drugs on nervous system tissue
• Includes Pharmakon meaning charm, poison, scapegoat, remedy/medicine
• Receptor antagonists inhibit neurotransmitter receptors
• ACh example: curare
• Receptor agonists mimic actions of naturally occurring neurotransmitters
• ACh example: nicotine

Synaptic Integration

• Synaptic integration is the process by which multiple synaptic potentials combine within one postsynaptic neuron
• Most CNS neurons receive thousands of synaptic inputs
• Synaptic integration is a form of neural computation

Principles of Synaptic Integration

• EPSP summation allows for neurons to perform sophisticated computations
• Integration: EPSPs are added together to produce significant postsynaptic depolarization
• Spatial summation: EPSPs are generated simultaneously at different sites
• Temporal summation: EPSPs are generated at the same synapse in rapid succession

Contribution of Dendritic Properties to Synaptic Integration

• A simplified view is that a dendrite can be viewed as a straight cable
• Membrane depolarization falls off exponentially with increasing distance along the cable
• In reality, dendrites are very elaborate structures that contribute to more complex integrative properties

Inhibition

• Not all synapses are excitatory
• Action of inhibitory synapses takes membrane potential away from the action potential threshold and exerts powerful control over neuron output
• Different neurotransmitters bind to excitatory vs. inhibitory synapses and allow different ions to pass through channels
• Shunting inhibition: Synapse inhibits current flow from soma to axon hillock
• Cl⁻ moves in

Geometry of Excitatory and Inhibitory Synapses

• Excitatory synapses use glutamate
• Gray's type I morphology (asymmetrical) is used in Excitatory synapses
• Inhibitory synapses use GABA or glycine
• Gray's type II morphology (symmetrical) is used in Inhibitory synapses
• Inhibitory synapses are found on dendrites, clustered on soma and near the axon hillock

Concluding Remarks

• Chemical synaptic transmission offers rich diversity
• It allows for complex behaviors
• 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