Computational modeling of medium spiny projection neurons in nucleus accumbens: toward the cellular mechanisms of afferent stream integration

Abstract

The nucleus accumbens (Nacc) regulates the major feedback pathways linking prefrontal cortex, hippocampus, and amygdala. We describe simulations of a biophysical level model of a single medium spiny projection (MSP) neuron, the principle cell of the Nacc. The model suggests that the unusual bistable membrane potential of MSP cells arises from the interplay between two potassium currents, K IR and K A . We find that the transition from the membrane potential down state (~-85mV) to the upstate (~-60mV)requires a significant barrage of synchronized inputs, and that ongoing afferent stimulation is required to maintain the cell in the up state. The Nacc receives the densest dopaminergic innervation in the brain, and the model demonstrates, in agreement with recent experimental evidence, that dopamine acts to increase the energy barrier to membrane potential state transitions. Through its action on K IR and L-type Ca 2+ channels, dopamine selectively lowers cell gain in the down state and increases it in the up state, a mechanism for context-dependent gain control.These findings suggest a mechanism of afferent pattern integration in the accumbens arising from transient synchronization among ensembles of MSP neurons. We attempt to relate these findings to possible origins of abnormalities of sensory gating in schizophrenia. KeywordsBistability, frontal cortex, medium spiny projection (MSP) neuron, modeling, simulation, striatum. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of the University of Pennsylvania's products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to pubs-permissions@ieee.org. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.

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