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Authors & Affiliations
Patricia Molina Molina, Sarah Mondoloni, Mauro Congiu, Manuel Mameli
Abstract
The increasing prevalence of psychiatric disorders, such as depression, highlights the need to elucidate their underlying neurobiological mechanisms. The lateral habenula (LHb) and its neuronal activity contribute to the pathophysiology of depression when dysfunctional. Among the existing rodent models of depression, chronic corticosterone administration for 3-4 weeks recapitulates relevant behavioural aspects of the disease such as anhedonia and increased passive coping. However, the temporal emergence of these features and the cellular underpinnings remain unclear. Thus, we assessed the emergence of specific behavioural phenotypes and their potential neuronal correlates in the LHb over the course of chronic corticosterone treatment. The corticosterone-treated group displayed reduced grooming in the splash test already after 1 day of treatment, which persisted after 7 and 21 days. Despair-like behaviour, measured with the tail suspension test, and reduced active coping manifested instead after 7 days. Next, we injected mice with a viral vector expressing the calcium indicator GCaMP8m and implanted a GRIN lens in the LHb to track the calcium dynamics of individual neurons in response to an aversive stimulus (airpuff). Two-photon recordings were conducted at baseline and after 1, 7, 14, and 21 days of corticosterone administration. Analysis of ~100 LHb neurons revealed adaptations in their response to airpuff that developed throughout the treatment. In summary, our findings suggest that discrete temporal features emerge at the behavioural and cellular levels in a mouse model of depression.