The Functions of Cholinergic Neurotransmission in the Nucleus Accumbens

Abstract

The nucleus accumbens (NAc) has long been regarded as essential brain structure for learning and motivated behavior. Acetylcholine (ACh), from local cholinergic interneurons, comprise a significant source of neuromodulation in the NAc. Though how these cholinergic interneurons function in the striatum is not fully understood, they have been shown to encode both salient and reward-related stimuli and have been implicated in supporting certain forms of learning. This thesis attempts to improve our characterizations of this neuromodulatory population and expand our understanding of its role in learning and behavior. In the case of cholinergic interneurons, while recent work has demonstrated the necessity of cholinergic transmission to reward-context learning several gaps remain in our understanding of this neuromodulator. A causal role for cholinergic activation, for instance, has not been convincingly shown in the striatum for Pavlovian reward learning and acetylcholine’s relationship to neural plasticity is not well characterized. Using optogenetic approaches to resolve these problems, we demonstrate how striatal cholinergic activation influences reward-context learning. Using ex-vivo electrophysiology, we then examine how cholinergic mediated changes in learning correspond to synaptic plasticity. These are the first findings that convincingly link changes in cholinergic activation with learning and plasticity.