A Model for the Action of NMDA Conductances in the Visual Cortex

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Abstract
A model is presented for the behavior of N-methyl-D-aspartate (NMDA) receptors during neuronal responses to visual stimuli in visual cortex based on classical steady-state equations for membrane conductance, and for binding of transmitter with NMDA and non-NMDA receptors. Constraints in the equations and the equation for voltage dependency of the NMDA receptors come from measurements in hippocampus, embryonic CNS neurons, and cortex. An excitatory amino acid transmitter released from terminals in the visual cortex is assumed to be related to the contrast of the stimulus by a hyperbolic tangent formula. The transmitter is assumed to be glutamate. The model is a two compartment representation of a single neuron at steady state. The model fits results obtained from contrast-response curves measured in the visual cortex in control conditions and with iontophoresis of NMDA and non-NMDA agonists or antagonists. The model shows how NMDA receptors contribute to the visual response in a graded multiplicative fashion at all levels of contrast. NMDA receptors do not show switch behavior, that is, they are not turned on at high levels of stimulation only. The difference in NMDA receptor current between low and high levels of stimulation cannot be accounted for solely by the voltage dependency of the NMDA receptor. One needs, in addition, another factor, such as a difference in the Hill coefficient for binding of glutamate at the NMDA receptor.