Study of the role of the lateral habenula in fear conditioning and stress response in rat

Adapting our behavioral response when facing a threating environment is essential to survival. This ability is supported by a wide brain network. The lateral habenula (LHb) seems to be an important structure of the stress response as it shows important activation in the presence of various stressors; it is postulated to interact with limbic structures such as the medial prefrontal cortex, the extended amygdala, and the hippocampus in order to participate to stress coping. However, these interactions remain poorly explored. The goal of my PhD project was to study in rats the role of the LHb in the stress response and how it is integrated into the wide network supporting such response, at the emotional, cognitive, and behavioral levels. In a first study, we demonstrated the implication of the LHb in fear memory, as well as its interaction with the key limbic structures engaged in this process. In our second study, we explored the functional network engaged during restraint stress and found the close interaction between the LHb and the whole stress response network, also including monoaminergic systems, suggesting the LHb contributes to the balance of the monoaminergic control over key limbic structures involved in the stress response. In our last study, using local field potential recordings, we discovered that the LHb was differentially engaged during the different steps of the response to immobilization stress, whether they take place during periods of active waking, or during sleep. Altogether, these results increase our knowledge of the engagement of the LHb in stress coping, in coordination with the key limbic regions involved in emotional processes; they further support the idea that this structure is a crucial hub of information integration, updating the network supporting the stress response.