COMPUTATIONAL MODELS OF NMDA-RECEPTORS IN VISUAL CORTEX

The goals of this proposal are to contribute to the understanding of the circuitry and synaptic mechanisms underlying the function of the cerebral cortex. Since this is the brain structure responsible for much of our conscious perception and action and of our "higher" mental functions, the implications for mental health of such understanding are profound. Excitatory transmission in the cerebral cortex is mediated primarily by glutamate receptors. The N-methyl-D-aspartate (NMDA) receptor is one of at least two subtypes of these. It is unique among glutamate receptors in that the channel it activates has a voltage-dependent conductance under physiological conditions, and the currents it activates have a very slow time course. Recent work has revealed that excitatory transmission in visual cortex depends critically on NMDA receptors. This proposal's aim is to theoretically examine the effects of this dependence on the computational properties of individual visual cortical cells and on model visual cortical networks. This will be accomplished through biophysically detailed computer modeling. Specifically, the aims are: (1) To develop a limited set of candidate biophysical models for NMDA-receptor mediated synaptic activation, through detailed single-cell modeling, constrained by observations at both the biophysical and the physiological level; (2) To combine these NMDA models with existing models of visual cortical circuitry, in order to develop unified, consistent, testable models capable of explaining experimental observations of visual cortical spatio/temporal response properties.