Post-tetanic potentiation involves the presynaptic binding of calcium to calmodulin

A subset of synaptic vesicles undergoes exocytosis upon Ca 2+ influx into the presynaptic terminal. This group of vesicles constitutes a readily releasable pool (RRP) of ves-icles, which is replenished from a larger reserve pool of vesicles. The RRP is thought to represent the vesicles docked to the nerve terminal membrane at active zones (Fig. 1). During a prolonged depolarizing pulse–mediated stimulation, the RRP can be divided into two separate pools: a fast-releasing pool that recovers slowly, and a slowly releasing pool that recovers quickly (Neher and Sakaba, 2008). The size of an RRP is a key determinant of a synapse's efficacy, or synaptic strength, and fluctuations in pool fullness determine in part the synaptic strength during ongoing stimulation. However, the previous history of synaptic use can alter the size of the RRP. For example , the number of vesicles released by an action potential can increase after repetitive stimulation, via an increase in release probability and/or RRP size (Zucker and Regehr, 2002). Such short-term facilitation and post-tetanic potentiation (PTP) were first recognized in the frog neuromuscular junction and were thought to be due to Ca 2+ accumulation in the presynaptic nerve terminal (Feng, 1941; Rosenthal, 1969). Recently, an increasing number of studies indicate that diverse signaling mechanisms are involved in the trafficking, docking, and fusion of vesicles (Atwood and Karunanithi, 2002). These mechanisms thus have the potential to regulate short-term plasticity. The calyx of Held, a giant glutamatergic synapse in the auditory brainstem, is an accessible central nervous system model synapse for studying short-term plasticity because direct patch clamp recordings can be made from the presynaptic terminal and its postsynaptic neuron, the principal cell of the medial nucleus of the trapezoid body. During high-frequency repetitive activity, excit-atory postsynaptic currents at the calyx of Held undergo severe frequency-dependent depression (Borst et al., 1995). This short-term depression has a presynaptic origin because it is due to synaptic vesicle pool depletion (von Gersdorff et al., 1997). Interestingly, after a prolonged 5-second train of action potentials at 100 Hz, this synapse also exhibits PTP (Habets and Borst, 2005; Korogod et al., 2005). What is the mechanism underlying PTP? An increase in release probability (Pr), or an increase in RRP, or an increase in both? These two parameters can be modulated independently during PTP as indicated by the finding that a small depolarization of the calyceal terminal (resulting in a submicromolar elevation of basal …