Ein semi-mikroskopisches Modell synaptischer Übertragung und Plastizität

A stochastic model of synaptic transmission has been designed on the basis of electro-physiological experiments. Monte Carlo simulations are performed which include presynaptic mechanisms of recruitment and calcium related release of vesicles, transmitter dynamics in the cleft and postsynaptic receptor kinetics. The model of presynaptic vesicle dynamics has been designed on the basis of experimentally observed patterns of synaptic depression (and facilitation) at the Calyx of Held in the mammalian auditory pathway. It comprises two types of vesicles, readily-releasable vesicles and in addition reluctantly-releasable vesicles, as well as facilitation of release as consequence of changes in the global residual calcium accumulating during previous repetitive activity. It is demonstrated that the transmitter dynamics within the cleft can be effectively modeled by a two-dimensional diffusion process, where absorbing boundary conditions reflect the effect of transmitter uptake by transporters and diffusion into extra-synaptic space. The transmitter diffusion within the cleft is slowed down compared to aqueous solution and an estimate of the effective diffusion coefficient is provided. The neurotransmitter interacts with individual spatially distributed receptors, which are included in the model on the basis of kinetic Markov models. The modeling steps of presynaptic vesicle dynamics, transmitter motion in the cleft and its interaction with postsynaptic receptors are combined to create a model of a single synaptic connection between two neurons. Postsynaptic responses are studied as function of input-frequency and possible physiological determinants. It is shown that the specific combination of release-probability, receptor desensitization and presynaptic release-machinery determines whether synaptic connections facilitate or depress and sets the range of input-rates, i.e. frequencies that can be transmitted towards the postsynaptic side