Evidence for synaptic plasticity in the mammalian nervous system is widespread and also occurs on timescales ranging from milliseconds to days, weeks, or longer. Although these changes occur throughout the brain, short-term forms of plasticity that last for minutes or less have been studied in greatest detail at peripheral neuromuscular synapses.

Repeated activation of the neuromuscular junction triggers several sorts of change that vary in both time course and direction (Figure 25.3). Synaptic facilitation, which is a transient increase in synaptic strength, occurs when two or more action potentials invade the presynaptic terminal in close succession. Facilitation results in more neurotransmitter being released by each succeeding action potential, causing the postsynaptic end plate potential (EPP) to increase progressively. Much evidence suggests that synaptic facilitation is the result of prolonged elevation of presynaptic calcium levels following synaptic activity. Although the entry of Ca²⁺ into the presynaptic terminal occurs within a millisecond or two after an action potential invades (see Chapter 5), the mechanisms that return calcium to resting levels are much slower. Thus, when action potentials arrive close together in time, calcium builds up within the terminal and allows more neurotransmitter to be released by a subsequent presynaptic action potential. A high-frequency burst of presynaptic action potentials (colloquially referred to as a “tetanus”) can yield even more prolonged elevation of presynaptic calcium levels, causing another form of synaptic enhancement called post-tetanic potentiation (PTP). PTP is delayed in its onset and typically persists for some minutes after the train of stimuli ends. The difference in duration distinguishes PTP from synaptic facilitation. PTP is thought to arise from calcium-dependent processes that make more synaptic vesicles available for transmitter release.

Synaptic transmission also can be diminished following repeated synaptic activity. Such synaptic depression occurs when many presynaptic action potentials occur in rapid succession and depends on the amount of neurotransmitter that has been released (see Figure 25.3). Depression arises because of the progressive depletion of the pool of synaptic vesicles available for fusion in this circumstance. During synaptic depression, the strength of the synapse declines until this pool can be replenished via the mechanisms involved in recycling of synaptic vesicles (see Chapter 5).

During repeated synaptic activity, these various forms of plasticity can interact in complex ways. For example, at the neuromuscular synapse, repeated activity first facilitates synaptic transmission; then depletion of synaptic vesicles allows depression to dominate and weaken the synapse (see Figure 25.3). After the stimulus train ends, the invasion of the terminal by another action potential causes enhanced transmitter release (i.e., post-tetanic potentiation).

These forms of short-term plasticity are observed at virtually all chemical synapses and continually modify synaptic strength. Thus, the efficacy of chemical synaptic transmission changes dynamically as a consequence of the recent history of synaptic activity.