Dottorato in GENETICA E BIOLOGIA MOLECOLARE

Titolo della tesi: A Hypothalamic Micro-Circuit for Social Escape Decision Making

Animals display a wide range of behaviours that are in service to their survival, some of the most critical of which are defensive behaviours. These behavioural strategies help the animals cope with dangerous situations, and the exact behavioural choice depends upon the context and nature of threat. Some of the behavioural strategies such as active avoidance, passive defence and aggression are thought to be mediated by the centrally located hypothalamic nuclei constituting the medial hypothalamic defensive circuit. One of these is the Ventromedial Hypothalamus (VMH) which has been implicated in avoidance and attack directed towards threats. Even as the VMH has been implicated in modulating such behaviours, how it might threshold a transition to escape is unclear. In this thesis, I investigated the micro-circuit within the ventrolateral subdivision of the VMH (VMHvl) in mice that have a history of social defeat, as they faced a social threat and displayed avoidance. Using in vivo electrophysiology recordings in a novel behavioural test introduced here, I recorded from the VMHvl of male and female mice to find the neural correlates of avoidance. In combination to the extracellular recordings, I used optogenetic stimulation of targeted cell classes - namely the motor output cells and the inhibitory cells in the male VMHvl, to map out the connectivity within the micro-circuit and verify a proposed connectivity model for escape decision making. Using the activity dynamics of the correlates of avoidance, I propose a combinatorial encoding with which the cells within the male VMHvl might bring about assessment as well as avoidance behaviours, in the current context. Finally, I confirmed the presence of cells in female mice which modulated their activity with social avoidance in a manner similar to that seen in males. These results suggest a role of the VMHvl in setting an escape threshold in both the male and the female brain, under conditions of social fear.