A role of prefrontal inputs to lateral hypothalamus in coping with stress

Stress is an adaptive mechanism that enables an optimal response to danger. However, chronic stress disrupts normal bodily functions and can lead to various disorders. The medial prefrontal cortex (mPFC) is involved in the regulation of stress responses. One of the output targets of the mPFC is the lateral hypothalamus (LH), a brain region that regulates innate behaviours known to be affected by stress. In this work, we analysed effects of optogenetic stimulation of mPFC inputs to LH on innate behaviours in freely behaving mice exposed to different stressors.Optogenetic stimulation of mPFC projections to the LH in unstressed mice promoted social interactions at the expense of feeding behaviour. However, following acute food restriction the stimulation had opposite effects, changing the balance between consumption and social interactions in favour of consumption. This effect was not detected following prolonged food restriction. When mPFC projections to the LH were stimulated during acute restraint, we observed reduced time in the shelter, as well as increased sociability.Thus, the activation of mPFC inputs to LH promoted behaviours that alleviated stress, such as food seeking following fasting or seeking out conspecifics following restraint. An increase in sociability in response to stress could reflect social buffering, an active coping behaviour engaged to overcome distress. Hence, mPFC input to LH can promote adaptation in response to stress.We gratefully acknowledge support by the ERC Consolidator Grant (772994, FeedHypNet, to T.K.) and the DFG (233886668-GRK1960, to R.F., Project-ID 431549029 – SFB 1451, to T.K., EXC2030 CECAD, to T.K.).