MONTE-CARLO SIMULATION OF FAST EXCITATORY SYNAPTIC TRANSMISSION AT A HIPPOCAMPAL SYNAPSE

1. A simulation of fast excitatory synaptic transmission at a hippocam pal synapse is presented. Individual neurotransmitter molecules are fo llowed as they diffuse through the synaptic cleft and interact with th e postsynaptic receptors. The ability of the model to reproduce publis hed results of patch-clamp experiments on CA3 pyramidal cells is illus trated; parameters of the model that affect the time course and variab ility of the excitatory postsynaptic current (EPSC) are then investiga ted. 2. To simulate an EPSC, we release 4,000 neurotransmitter molecul es simultaneously from a point source centered 15 nm above a rectangul ar grid of 14 x 14 postsynaptic receptors. The simulated EPSC at room temperature has a 10-90% rise time of 0.28 ms and a peak open probabil ity of 0.27, and decays with a time constant of 2.33 ms, comparing wel l with values in the literature. 3. To simulate changes in temperature , we use a 10 degrees temperature coefficient (Q(10)) for diffusion of 1.3 and apply a Q(10) of 3.0 to all the rate constants of the kinetic scheme. At 37 degrees C, the 10-90 rise time is 0.07 ms, the peak ope n probability is 0.56, and the decay time constant is 0.70 ms. The coe fficient of variation (CV) at the peak of the EPSC is 9.4% at room tem perature; at 37 degrees C, the CV at the peak drops to 6.6%. 4. We use the diffusion coefficient of glutamine, 7.6 X 10(-6) cm(2)/s, to mode l the random movement of glutamate molecules in the synaptic cleft. Sl ower rates of diffusion increase the peak response and slow the time c ourse of decay of the EPSC. 5. Random variations in release site posit ion have little effect on the time course of the average EPSC or on th e CV of the peak response. We simulate a dose-response curve for the e ffects of releasing between 100 and 7,500 neurotransmitter molecules p er vesicle. The half-maximal response occurs for 1,740 molecules. For a simulation with 100 postsynaptic receptors and a diffusion coefficie nt of 2.0 X 10(-6) cm(2)/s, 4,000 molecules approaches a saturating do se. 6. Changes to the width of the synaptic cleft, or to the number an d spacing of the postsynaptic receptors, have marked effects on the pe ak height of the simulated EPSC. 7. We extend the model to include a s pherical vesicle (50 nm diam) connected to the synaptic cleft by a cyl indrical pore 15 nm long. Neurotransmitter molecules are randomly dist ributed within the vesicle and allowed to diffuse into the synaptic cl eft through the pore, which opens to its full diameter in one time ste p. We find that the pore must open to a diameter of greater than or eq ual to 7 nm within 1 mu s in order to match the time courses of EPSCs in the literature.