Passlack, Jessica; (2024) Role of Nucleus Reuniens in flexible behaviour dependent on cues and outcomes. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The ability to flexibly adjust our decision-making is vital for navigating a complex world where the best decisions depend on the current context. Crucially, there are two distinct strategies supported by two distinct brain regions that can be used to identify the current context. The prefrontal cortex (PFC) reacts to the observed outcomes of behaviours to identify which behaviours are currently relevant. In contrast, the hippocampus (HPC) uses information from the environment around us in the form of predictive cues to predict the current relevant behaviour. Crucially, it is thought that the bidirectional connection of the PFC and HPC through the nucleus reuniens of the thalamus (nRE) is vital for performing such contextual inference. However, little is known about how interaction of PFC and HPC via nRE guides behaviour. To address this, we used a cued T-maze in mice, where a cue at the beginning of the maze indicates the reward location. First, using circuit tracing, we found that largely non-overlapping nRE populations project only to either PFC or HPC, as well as receiving distinct inputs. On this basis, we next investigated what role these parallel circuits in nRE play in behaviour. We found that inhibition of nRE projectors to PFC, but not to HPC, during learning led mice to switch from a predictive cue- based strategy to an outcome-based strategy. Contrastingly, manipulation of nRE projectors to HPC, but not PFC, following learning led mice to switch from a predictive to an outcome-based strategy. Next, we used computational models of PFC and HPC which learnt to perform Bayesian inference over either outcome-or cue-focused model-based representations to show that nRE activity is crucial to balance the contributions of HPC and PFC during contextual inference. Together, our results indicate that nRE mediates between predictive HPC strategies and outcome-based PFC strategies for contextual inference.

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