Microcircuit Mechanisms Regulating Nucleus Accumbens Circuit Function

Abstract

The nucleus accumbens (NAc) is implicated in the pathogenesis of conditions characterized by maladaptive motivational states, including addiction and depression. Embedded within the mesolimbic network, the NAc coordinates reward-related behavioral output by integrating ascending neuromodulatory input with glutamatergic afferents from cortical and allocortical limbic structures. While intense research has focused on how extrinsic monoaminergic signaling gates synaptic adaptations in the NAc, comparatively little is known how local microcircuitry within the NAc calibrates mesolimbic circuit output to shape goal-directed behaviors. Parvalbumin-expressing interneurons (PV-IN) in the NAc, a fast-spiking GABAergic interneuron with distinct biophysical properties, regulate principal medium spiny neuron (MSN) activity via feedforward inhibitory microcircuits. In this dissertation, cellular and synaptic mechanisms governing PV-IN-embedded microcircuit function are examined at feedforward synapses within the NAc core subterritory. Understanding how circuit elements within PV-IN microcircuits contribute to adaptive and maladaptive reward behavior will hopefully aid in the development of novel therapeutics for motivational disorders