Shortterm Changes in Synaptic Strength

The size of the postsynaptic response produced by a particular synaptic input in the nervous system is not fixed but instead varies, depending on the past history of activity at that particular synapse. This variation in the strength of a synaptic connection is called synaptic plasticity. The presynaptic facilitation of transmission produced by serotonin in Aplysia sensory neurons described in the preceding paragraph is one example of synaptic plasticity. In addition to enhancement of synaptic strength, synaptic plasticity sometimes involves a decline in the effectiveness of a synaptic connection. Some presynaptic factors that generate synaptic depression are summarized in Figure 9-16. During a series of presynaptic action potentials, the pool of synaptic vesicles available for release may become depleted, causing the amount of neurotransmitter released to decline with time (Figure 9-16a). In addition, accumulation of calcium inside the presynaptic terminal during a series of action potentials can depress further neurotransmitter release by closing calcium channels (Figure 9-16b; also see Chapter 12). Calcium-dependent inactivation of calcium channels reduces the amount of calcium entering during a presynaptic action potential and thus decreases the amount of neurotransmitter released. Accumulation of calcium in the presynaptic terminal can also open calcium-activated potassium channels (see Chapter 6), which would depress neurotransmitter release by hyperpolarizing the terminal and promoting rapid repolarization following an action potential.

Figure 9-16 Three mechanisms for synaptic depression. (a) After repetitive presynaptic action potentials, the pool of releasable synaptic vesicles can become depleted, leaving fewer vesicles available to respond to subsequent action potentials. (b) Accumulation of calcium ions inside the terminal can inactivate calcium channels (negative sign), or activate calcium-sensitive potassium channels (plus sign). (c) The neurotransmitter molecules (NT) released by a synaptic terminal bind to autoreceptors on the surface of the terminal. The activated autoreceptors then activate G-proteins, leading to closure of voltage-dependent calcium channels (negative sign) or opening of potassium channels (plus sign). In addition, the postsynaptic cell contacted by the synaptic terminal can feed back either directly or indirectly and release a different neurotransmitter (X), which alters calcium and/or potassium channel opening.

Figure 9-16 Three mechanisms for synaptic depression. (a) After repetitive presynaptic action potentials, the pool of releasable synaptic vesicles can become depleted, leaving fewer vesicles available to respond to subsequent action potentials. (b) Accumulation of calcium ions inside the terminal can inactivate calcium channels (negative sign), or activate calcium-sensitive potassium channels (plus sign). (c) The neurotransmitter molecules (NT) released by a synaptic terminal bind to autoreceptors on the surface of the terminal. The activated autoreceptors then activate G-proteins, leading to closure of voltage-dependent calcium channels (negative sign) or opening of potassium channels (plus sign). In addition, the postsynaptic cell contacted by the synaptic terminal can feed back either directly or indirectly and release a different neurotransmitter (X), which alters calcium and/or potassium channel opening.

Feedback mechanisms are also thought to play a role in synaptic depression (Figure 9-16c). The neurotransmitter released by previous action potentials feeds back, either directly or indirectly, onto the releasing terminal and influences the release of transmitter by subsequent action potentials. Indirect feedback can occur via presynaptic inhibition, described previously in this chapter. Direct feedback can occur via autoreceptors in the plasma membrane of the presynaptic terminal. Autoreceptors are activated by neurotransmitter released from the synaptic terminal on which they are located. Because they are usually located in parts of the synaptic terminal at a distance from the synaptic cleft, autoreceptors are activated only when enough neurotransmitter is released to spill out of the synaptic cleft and reach the surrounding parts of the extracellular space. Autoreceptors are usually members of the G-protein-coupled family of receptors, linked indirectly to ion channels via intracellular second messengers. In some cases, the activated autoreceptors reduce neuro-transmitter release by closing calcium channels, which reduces the amount of calcium entering during a presynaptic action potential. In other cases, they are linked to the opening of potassium channels, which hyperpolarizes the terminal and speeds repolarization during a presynaptic action potential.

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