Computational Modeling of Medium Spiny Projection Neurons in Nucleus Accumbens: Toward the Cellular Mechanisms of Afferent Stream Integration

摘要

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, KIR and KA. 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 KIR and L-type Ca2+ 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.