CA1 spatial coding as a predictor for vulnerability to compulsive alcohol seeking

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Compulsive alcohol seeking and choice of alcohol-predicting contexts - that often result in relapse to alcohol consumption - are hallmarks of alcohol use disorders (AUD). While the neuronal networks driving these pathological behaviors are poorly understood, those supporting navigation towards rewards are likely to be important. Goal-oriented navigation in mammals relies on the use of internal representations of space produced in the dorsal hippocampus. Consistently, recent work has shown that activity of the dorsal hippocampus is driving spatial memory related to cocaine. It is thus natural to suppose that neuronal networks involving the dorsal hippocampus, also play a fundamental role in maladaptive alcohol seeking. Yet, studying these networks in laboratory animals has been prevented by many technical limitations: impossibility to track activity of a large number of neurons of live subjects, poor behavioral stratification of individuals, as well as lack of tools to precisely control the activity of specific brain circuits. Here, we propose to combine: (i) wide field head mounted microscopes to image neuronal activity of hundreds of pyramidal neurons in the dorsal CA1 area (dCA1) of mice, (ii) genetic and chemogenetic tools to label and manipulate neuronal networks with cell-type and projection specificity, (iii) a novel behavioral task and apparatus (E-maze) to investigate the dCAl representations during spatial planning, decision, navigation and consumption of alcohol and (iv) an established animal model of AUD. These methods will enable us to study whether dCA1 coding during alcohol seeking predicts the emergence of addicted-like behavioral phenotypes.