Synaptic Physiology

• A synapse is an anatomically specialized junction between two neurons, at which the electrical activity in a presynaptic neuron influences the electrical activity of a postsynaptic neuron
• There are more than 10^14 (100 trillion!) synapses in the CNS
• Activity at synapses


  Can increase or decrease the likelihood that the postsynaptic neuron will fire action potentials by producing a brief, graded potential in the postsynaptic membrane
• Excitatory synapse


  Brings the membrane potential of a postsynaptic neuron closer to threshold (depolarized)
• Inhibitory synapse


  Drives the membrane potential of a postsynaptic neuron farther from threshold (hyperpolarized) or stabilizes it at its resting potential
• Convergence


  Allows information from many sources to influence a cell’s activity
• Divergence


  Allows one cell to affect multiple pathways
• If the membrane of the postsynaptic neuron reaches threshold, it will generate action potentials that are propagated along its axon to the axon terminals, which in turn influence the excitability of other cells
• The level of excitability of a postsynaptic cell at any moment depends on the number of synapses active at any one time and the number that are excitatory or inhibitory
• Electrical synapses are extremely rapid in communication between cells
• Electrical synapses were formerly thought to be rare in the adult mammalian nervous system but have now been described in widespread locations
• Electrical synapses may have more important functions than previously thought, including synchronization of electrical activity of neurons clustered in local CNS networks and communication between glial cells and neurons
• Multiple isoforms of gap-junction proteins have been described, and the conductance of some of these is modulated by factors such as membrane voltage, intracellular pH, and Ca2+ concentration
• More research is required to gain a complete understanding of the modulation and all of the complex roles of electrical synapses in the nervous system
• The function of electrical synapses is better understood in cardiac and smooth muscle tissues
• The axon of the presynaptic neuron ends in slight swellings, the axon terminals, which hold the synaptic vesicles that contain neurotransmitter molecules
• The postsynaptic membrane adjacent to an axon terminal has a high density of membrane proteins that make up a specialized area called the postsynaptic density
• A 10 to 20 nm extracellular space, the synaptic cleft, separates the presynaptic and postsynaptic neurons
• Postsynaptic membrane adjacent to an axon terminal

  Has a high density of membrane proteins that make up a specialized area called the postsynaptic density
• Synaptic cleft


  A 10 to 20 nm extracellular space that separates the presynaptic and postsynaptic neurons and prevents direct propagation of the current
• Transmission of signals across the synaptic cleft

  By means of a chemical messenger - a neurotransmitter - released from the presynaptic axon terminal
• Cotransmitter


  An additional neurotransmitter released from an axon when more than one neurotransmitter is simultaneously released
• Excitatory synapse


  Brings the membrane of a postsynaptic cell closer to threshold
• Inhibitory synapse


  Prevents a postsynaptic cell from approaching threshold by hyperpolarizing or stabilizing the membrane potential
• Postsynaptic cell firing an action potential


  Depends on the number of synapses that are active and whether they are excitatory or inhibitory
• Electrical synapses


  Consist of gap junctions that allow current to flow between adjacent cells
• Neurotransmitter release


  Stored in small vesicles with lipid bilayer membranes, released when an action potential reaches the presynaptic terminal membrane
• Voltage-gated Ca2+ channels in neuron terminals

  Open during depolarization, allowing Ca2+ influx which triggers neurotransmitter release
• Neurotransmitters stored in synaptic vesicles

  Released by a presynaptic axon terminal into the synaptic cleft to transmit the signal to a postsynaptic neuron at a postsynaptic density
• Calcium ions activate processes that lead to the fusion of docked vesicles with the synaptic terminal membrane
• After fusion, vesicles can undergo at least two possible fates: completely fuse with the membrane and later recycled by endocytosis or fuse briefly and then reseal the pore and withdraw back into the axon terminal (kiss-and-run fusion)
• Depolarization of an axon terminal opens voltage-gated Ca2+ channels in the membrane
• Ca2+ diffuses through channels down its electrochemical gradient into the cytosol of the terminal
• Depolarization of an axon terminal

  1. Opens voltage-gated Ca2+ channels in the membrane

  2. Ca2+ diffuses through channels down its electrochemical gradient into the cytosol of the terminal
• What causes Ca2+ to enter the cytosol of an axon?
• Activation of the Postsynaptic Cell

  Neurotransmitters released from a presynaptic axon terminal diffuse across the cleft and interact with the postsynaptic cell
• Binding of Neurotransmitters to Receptors

  Neurotransmitters bind to receptors on the plasma membrane of the postsynaptic cell, leading to the opening or closing of specific ligand-gated ion channels in the postsynaptic plasma membrane
• There is a very brief synaptic delay of about 0.2 msec between the arrival of an action potential at a presynaptic terminal and the membrane potential changes in the postsynaptic cell
• Increased Ca2+ concentration


  Causes cytosolic proteins synaptotagmins and SNAREs to induce vesicles containing neurotransmitter to fuse with the plasma membrane, releasing neurotransmitter into the synaptic cleft
• Neurotransmitter binding to the receptor is transient and reversible