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  • Transmitter Release Is Regulated by Depolarization of the Presynaptic Terminal

  • Release Is Triggered by Calcium Influx

    • The Relation Between Presynaptic Calcium Concentration and Release

    • Several Classes of Calcium Channels Mediate Transmitter Release

  • Transmitter Is Released in Quantal Units

  • Transmitter Is Stored and Released by Synaptic Vesicles

    • Synaptic Vesicles Discharge Transmitter by Exocytosis and Are Recycled by Endocytosis

    • Capacitance Measurements Provide Insight into the Kinetics of Exocytosis and Endocytosis

    • Exocytosis Involves the Formation of a Temporary Fusion Pore

    • The Synaptic Vesicle Cycle Involves Several Steps

  • Exocytosis of Synaptic Vesicles Relies on a Highly Conserved Protein Machinery

    • The Synapsins Are Important for Vesicle Restraint and Mobilization

    • SNARE Proteins Catalyze Fusion of Vesicles with the Plasma Membrane

    • Calcium Binding to Synaptotagmin Triggers Transmitter Release

    • The Fusion Machinery Is Embedded in a Conserved Protein Scaffold at the Active Zone

  • Modulation of Transmitter Release Underlies Synaptic Plasticity

    • Activity-Dependent Changes in Intracellular Free Calcium Can Produce Long-Lasting Changes in Release

    • Axo-axonic Synapses on Presynaptic Terminals Regulate Transmitter Release

  • An Overall View

Some of the brain's most remarkable abilities, such as learning and memory, are thought to emerge from the elementary properties of chemical synapses, where presynaptic terminals release chemical transmitters that activate receptors in the membrane of the postsynaptic cell. In the last three chapters we saw how postsynaptic receptors control ion channels that generate the postsynaptic potential. Here we consider how electrical and biochemical events in the presynaptic terminal lead to the secretion of neurotransmitters. In the next chapter we examine the chemistry of the neurotransmitters themselves.

Transmitter Release Is Regulated by Depolarization of the Presynaptic Terminal

What are the signals at the presynaptic terminal that lead to the release of transmitter? Bernard Katz and Ricardo Miledi first demonstrated the importance of depolarization of the presynaptic membrane through the firing of a presynaptic action potential. For this purpose they used the giant synapse of the squid, a synapse large enough to permit insertion of electrodes into both pre- and postsynaptic structures. Two electrodes are inserted into the presynaptic terminal—one for stimulating and one for recording—and one electrode is inserted into the postsynaptic cell for recording the excitatory postsynaptic potential (EPSP), which provides an index of transmitter release (Figure 12–1A).

Figure 12–1
Transmitter release is triggered by changes in presynaptic membrane potential.

(Adapted, with permission, from Katz and Miledi 1967a.)

A. Voltage recording electrodes are inserted in both the pre- and postsynaptic fibers of the giant synapse in the stellate ganglion of a squid. A current-passing electrode is also inserted presynaptically to elicit a presynaptic action potential.

B. Tetrodotoxin (TTX) is added to the solution bathing the cell to block the voltage-gated Na+ channels that underlie the action potential. The amplitudes of both the presynaptic action potential and the excitatory postsynaptic potential (EPSP) gradually decrease as more and more Na+ channels are blocked. After 7 min the presynaptic action ...

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