Synapsin controls both reserve and releasable synaptic vesicle pools during neuronal activity and short-term plasticity in Aplysia

Neurotransmitter release is a highly efficient secretory process exhibiting resistance to fatigue and plasticity attributable to the existence of dist inct pools of synaptic vesicles (SVs), namely a readily releasable pool and a reserve pool from which vesicles can be recruited after activity. Synapt ic vesicles in the reserve pool are thought to be reversibly tethered to th e actin-based cytoskeleton by the synapsins, a family of synaptic vesicle-a ssociated phosphoproteins that have been shown to play a role in the format ion, maintenance, and regulation of the reserve pool of synaptic vesicles a nd to operate during the post-docking step of the release process. In this paper, we have investigated the physiological effects of manipulating synap sin levels in identified cholinergic synapses of Aplysia californica. When endogenous synapsin was neutralized by the injection of specific anti-synap sin antibodies, the amount of neurotransmitter released per impulse was una ffected, but marked changes in the secretory response to high-frequency sti mulation were observed, including the disappearance of post-tetanic potenti ation (PTP) that was substituted by post-tetanic depression (PTD), and incr eased rate and extent of synaptic depression. Opposite changes on post-teta nic potentiation were observed when synapsin levels were increased by injec ting exogenous synapsin I. Our data demonstrate that the presence of synaps in-dependent reserve vesicles allows the nerve terminal to release neurotra nsmitter at rates exceeding the synaptic vesicle recycling capacity and to dynamically change the efficiency of release in response to conditioning st imuli (e.g., posttetanic potentiation). Moreover, synapsin-dependent regula tion of the fusion competence of synaptic vesicles appears to be crucial fo r sustaining neurotransmitter release during short periods at rates faster than the replenishment kinetics and maintaining synchronization of quanta i n evoked release.