PHYSIOLOGICAL AND STATISTICAL APPROACHES TO MODELING OF SYNAPTIC RESPONSES
P.G. Patil, M. West, H.V. Wheal and D.A. Turner
Duke University
Synaptic function centers on the physiological behavior of individual and combined synaptic sites, defined at the anatomical level as a unit consisting of a single postsynaptic density and presynaptic release region. However, multiple synaptic sites are usually activated together in a physiological response, even between two individual neurons. These multiple sites may be either grouped together, as at the neuromuscular junction, or distributed spatially, as in a complex dendritic neuron. The physiological efficacy of responses at each synaptic site can be defined by a few critical parameters, including probability of release, postsynaptic site response amplitude ("quantal" amplitude), the degree of fluctuation around that characteristic amplitude ("quantal" variance) distributed both over time and between sites, and the efficacy of electrotonic conduction between the synaptic site of origin and the output or summation site. These parameters all vary as a highly dynamic process, fluctuating with the history of use at each synapse over short and long time frames, and between adjacent synaptic sites on dendritic trees. Such heterogeneity between synaptic responses can lead to summated synaptic responses which are difficult to interpret in terms of the behavior of each individual synaptic site. However, the influence of these various factors on synaptic plasticity at multiple time spans is critical to further understand mechanisms of development, memory and neuronal circuitry function. Statistical models for analysis of synaptic function have become increasingly sophisticated to account quantitatively for these diverse sources of variability in the explanation of physiological processes. We review the use of various statistical models, which are used to infer descriptions of synaptic release characteristics under appropriate physiological conditions, including a novel Bayesian analysis format, to investigate formally many of these sources of variability. Together, constrained physiological preparations and sophisticated statistical models have defined both the presence of considerable heterogeneity between synaptic sites and mechanisms, which may contribute to synaptic plasticity in the CNS.