Afferent Stream Integration in a Model of the Nucleus Accumbens

The Nucleus Accumbens (Nacc) receives convergent input from a number of structures including prefrontal cortex, hippocampus, and amygdala, as well as substantial dopaminergic modulation. The principle cell in the Nacc, the medium spiny projection neuron (MSP), has bistable properties that have been proposed as a primary mediator of the integrative properties in the Nacc. In order to determine the minimum biophysical properties required to generate a nonlinear "bistable" membrane potential, we constructed a 29 compartment MSP cell in GENESIS. This included an inward rectifying K+ (KIR), an A-current K+, HVA Ca2+ and suitable fast Na+ and delayed rectifier K+ channels. Various amounts and distributions of afferent input were examined to determine the amount of coincident input required to move the membrane from the "down" state (-85 mV) to the "up" state (-60 mV) and to fire the cell. The number of synchronous afferents required was substantially higher than previously estimated. We modeled the effect of dopaminergic modulation by increasing the conductance of the KIR and Ca2+ channels, demonstrating that the response to input is dependent on state. In parallel studies, in vivo extracellular recordings were obtained from Nacc and neocortex in anesthetized mice. Simultaneous recordings revealed that cortex and Nacc oscillate in synchrony. Lesions that disrupt slow oscillations in the cortex alter rhythmicity in the Nacc, suggesting interdependency of the mechanisms generating bistability.