Cortico-thalamo-hippocampal networks in alternative learning

Classical studies in perceptual decision-making have shown that animals and humans can effectively integrate previously learnt associations with current sensory inputs to select appropriate behavioural strategies. In naturalistic scenarios, contextual influences are an omnipresent modulator of decision-making. Yet, a mechanistic understanding of how contextual information is integrated into the selection of behavioural strategies has thus far remained elusive. A key impediment to a mechanistic understanding of the neural circuitry involved is the broad neuroanatomical distribution of the various brain regions shown to be involved in decision-making processes. The Retrosplenial cortex (RSC), a well-established integrative centre in the brain has been previously shown to be pivotal in spatial cognition, memory and decision-making. Utilising unbiased structural connectivity mapping from learning ensembles in the RSC, in conjunction with loss of function and behavioural rescue experiments, I identified distributed and functionally delineated network nodes in the Dorsal Subiculum and the Anteroventral (AV) and Laterodorsally (LD) nuclei of the thalamus that enable switching of behavioural strategies exclusively in context-dependent learning paradigms. Further, the direct convergence of these thalamic and hippocampal networks onto a newly identified and genetically tractable subpopulation of Cortico-Striatal neurons in the RSC enables the context-dependent updating of behavioural strategies. Taken together, these results identify a circuit module dedicated to context-related strategy updating embedded within a specific hippocampal-thalamo-cortical network.