Mathematical model of cellular mechanisms contributing to presynaptic facilitation.

Presynaptic facilitation of transmitter release from sensory neurons is an important mechanism contributing to nonassociative and associative learning in Aplysia. In a previous modeling study (28,29), we concluded that enhancement of the postsynaptic potential (PSP) during presynaptic facilitation is mediated by at least two processes; spike broadening, which has been observed experimentally, and a process that we modeled as mobilization of transmitter. In an effort to gain insight into the relative contribution of these two mechanisms of presynaptic facilitation, we have extended our earlier model to include more detailed descriptions of: a) the kinetics of the Ca2+ channel, b) the diffusion of Ca2+ through the cytoplasm, c) the process of transmitter release, and d) the PSP. The present quantitative model provides an accurate description of the input-output relationship for synapses of sensory neurons, and predicts changes in the shape of postsynaptic potentials as a function of mobilization and spike broadening. The results confirm and extend previous experimental studies (33) and indicated that cellular analogs of sensitization (facilitation of nondecremented responses) is mediated primarily by spike broadening; whereas, analogs of dishabituation (facilitation of depressed responses) require mobilization.