MONTE CARLO SIMULATION OF FAST EXCITATORY SYNAPTIC TRANSMISSION AT A HIPPOCAMPAL SYNAPSE. Wahl, L.M., C. Pouzat & K. J. Stratford. University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, United Kingdom, Laboratoire de Neurobiologie, Ecole Normale Sup[theta]rieure, 46 rue d'Ulm, 75005 Paris, France, Tel : -44 (865) 272535 / 272500; Fax : -44 (865) 272469.
APStracts 2:0285N, 1995.
SUMMARY AND CONCLUSIONS
1. A simulation of fast excitatory synaptic transmission at a hippocampal synapse is presented. Individual neurotransmitter molecules are followed as they diffuse through the synaptic cleft and interact with the post-synaptic receptors. The ability of the model to reproduce published results of patch clamp experiments on CA3 pyramidal cells is illustrated; parameters of the model which affect the time course and variability of the excitatory post- synaptic current (EPSC) are then investigated. 2. To simulate an EPSC, we release 4000 neurotransmitter molecules simultaneously from a point source centered 15 nm above a rectangular grid of 14x14 post-synaptic receptors. The simulated EPSC at room temperature has a 10-90 rise time of 0.28 ms, a peak open probability of 0.27, and decays with a time constant of 2.33 ms, comparing well with values in the literature. 3. To simulate changes in temperature, we use a Q10 for diffusion of 1.3, and apply a Q10 of 3.0 to all the rate constants of the kinetic scheme. At 37°C, the 10-90 rise time is 0.07 ms, the peak open probability 0.56, and the decay time constant 0.70 ms. The coefficient of variation (CV) at the peak of the EPSC is 9.4% at room temperature; at 37°C, the CV at the peak drops to 6.6%. 4. We use the diffusion coefficient of glutamine, 7.6 x 10-6 cm2/s, to model the random movement of glutamate molecules in the synaptic cleft. Slower rates of diffusion increase the peak response and slow the time course of decay of the EPSC. 5. Random variations to release site position have little effect on the time course of the average EPSC or on the CV of the peak response. We simulate a dose-response curve for the effects of releasing between 100 and 7500 neurotransmitter molecules per vesicle. The half maximal response occurs for 1740 molecules. For a simulation with 100 post-synaptic receptors and a diffusion coefficient of 2.0 x 10-6 cm2/s, 4000 molecules approaches a saturating dose. 6. Changes to the width of the synaptic cleft, or to the number and spacing of the post-synaptic receptors, have marked effects on the peak height of the simulated EPSC. 7. We extend the model to include a spherical vesicle (50 nm diameter) connected to the synaptic cleft by a cylindrical pore, 15 nm long. Neurotransmitter molecules are randomly distributed within the vesicle and allowed to diffuse into the synaptic cleft through the pore, which opens to its full diameter in one timestep. We find that the pore must open to a diameter of at least 7 to 10 nm within 1 ms in order to match the time courses of EPSCs in the literature. 

Received 13 March 1995; accepted in final form 12 September 1995.
APS Manuscript Number J162-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95