An aspect often neglected in theoretical and experimental neurophysiological studies of the neocortex is that neurons in vivo are subject to an intense """"""""synaptic bombardment"""""""", which probably has important consequences for their integrative properties. This is corroborated by their high level of spontaneous activity together with the dense synaptic connectivity present in the neocortex. By contrast, the same neurons recorded in vitro show very low levels of spontaneous activity. Quantitative estimates of synaptic bombardment are thus needed to extrapolate the precise data obtained in vitro in order to build a correct model of the electrophysiological properties of neurons in vivo. Unfortunately, this data is presently unavailable. This project proposes a quantitative investigation of the synaptic bombardment in the neocortex in vivo by combining computational models with intracellular recordings of morphologically-identified pyramidal neurons. First, the conductance change and membrane potential fluctuations associated to spontaneous synaptic activity will be quantified from intracellular recordings obtained before and after microperfusion of tetrodotoxin or synaptic blockers. Second, the morphology of recorded neurons will be integrated into biophysical models to estimate synaptic conductance changes in soma and dendrites due to synaptic bombardment. Third, models will be used to study the consequences of synaptic bombardment for synaptic integration in pyramidal cells. Finally, the dendritic tree will be reduced to generate simplified models that capture the most salient features of synaptic integration under conditions of synaptic bombardment. This rare combination of models and in vivo recordings should lead to the generation of more accurate single-neuron models for use in network simulations. The potential impact of this study for the modeling community is therefore broad, from models of information processing to the simulations of pathological states, such as epilepsy.
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