Hippocampal interactions with striatal subnetworks for reward prediction and evaluation

Project Summary Drug addiction is a debilitating disorder that represents a significant public health burden. It is widely believed that addiction hijacks normal processes within the brain that assign reward values to past and future actions. These processes are not understood, which has hindered our ability to identify effective therapeutic targets. Part of the brain known as the ventral striatum (VS) has been shown to encode reward values, but it is not known how these value representations are linked to specific past or future actions, or how the functional implementations of reward evaluation and prediction are subdivided among different neuronal cell types within the VS. In this proposal, we address these questions by studying interactions between the VS and the hippocampus (HPC), one of its major inputs. In specific aim 1, we will test the hypothesis that coordinated activity between the HPC and the VS that occurs after reward collection is involved in linking the reward value to the previous action and updating the brain’s estimate of how valuable that reward was. In specific aim 2, we will test the hypothesis that HPC-VS interactions before reward collection are involved in choosing among several possible actions based on which has the highest predicted reward value. In specific aim 3, we will test the hypothesis that the neuronal populations in VS that interact with HPC before or after reward collection are genetically distinct neuronal subtypes. We expect this project will contribute broadly to our knowledge of how the brain evaluates past rewards and predicts future rewards, which may identify new therapeutic targets for treating drug addiction.