Simulations of the Role of the Muscarinic-Activated Calcium-Sensitive Nonspecific Cation CurrentINCMin Entorhinal Neuronal Activity during Delayed Matching Tasks

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Abstract
Entorhinal lesions impair performance in delayed matching tasks, and blockade of muscarinic cholinergic receptors also impairs performance in these tasks. Physiological data demonstrate that muscarinic cholinergic receptor stimulation activates intrinsic cellular currents in entorhinal neurons that could underlie the role of entorhinal cortex in performance of these tasks. Here we use a network biophysical simulation of the entorhinal cortex to demonstrate the potential role of this cellular mechanism in the behavioral tasks. Simulations demonstrate how the muscarinic-activated calcium-sensitive nonspecific cation current INCM could provide a cellular mechanism for features of the neuronal activity observed during performance of delayed matching tasks. In particular, INCM could underlie (1) the maintenance of sustained spiking activity during the delay period, (2) the enhancement of spiking activity during the matching period relative to the sample period, and (3) the resistance of sustained activity to distractors. Simulation of a larger entorhinal network with connectivity chosen randomly within constraints on number, distribution, and weight demonstrates appearance of other phenomena observed in unit recordings from awake animals, including match suppression, non-match enhancement, and non-match suppression.