THE EFFECTS OF GEOMETRICAL PARAMETERS ON SYNAPTIC TRANSMISSION - A MONTE-CARLO SIMULATION STUDY

Monte Carlo simulations of transmitter diffusion and its interactions with postsynaptic receptors have been used to study properties of quan tal responses at central synapses. Fast synaptic responses characteris tic of those recorded at glycinergic junctions on the teleost Mauthner cell (time to peak similar to 0.3-0.4 ms and decay time constant simi lar to 3-6 ms) served as the initial reference, and smaller contacts w ith fewer postsynaptic receptors were also modeled. Consistent with ex perimental findings, diffusion, simulated using a random walk algorith m and assuming a diffusion coefficient of 0.5-1.0 x 10(-5) cm(2) s(-1) , was sufficiently fast to account for transmitter removal from the sy naptic cleft. Transmitter-receptor interactions were modeled as a two- step binding process, with the double-bound state having opened and cl osed conformations. Addition of a third binding step only slightly dec reased response amplitude but significantly slowed both its rising and decay phases. The model allowed us to assess the sources of response variability and the likelihood of postsynaptic saturation as functions of multiple kinetic and spatial parameters. The method of nonstationa ry fluctuation analysis, typically used to estimate the number of func tional channels at a synapse and single channel current, proved unreli able, presumably because the receptors in the postsynaptic matrix are not uniformly exposed to the same profile of transmitter concentration . Thus, the time course of the probability of channel opening most lik ely varies among receptors. Finally, possible substrates for phenomena of synaptic plasticity, such as long-term potentiation, were explored , including the diameter of the contact zone, defined by the region of pre-and postsynaptic apposition, the number and distribution of the r eceptors, and the degree of vesicle filling. Surprisingly, response am plitude is quite sensitive to the size of the receptor-free annulus su rrounding the receptor cluster, such that expansion of the contact zon e could produce an appreciable increase in quantal size, normally attr ibuted to either the presence of more receptors or the release of more transmitter molecules.