An unpredicted salient event – rewarding or aversive – triggers a rapid emotional reaction that has profound impact in making a future choice. The early neurobiological processes behind it are matter of intense study. However, the hierarchical anatomical and functional organization as well as the cellular mechanisms underlying acute perception of reward and aversive events remains unknown. Intriguingly, salience experience alters the activity in the medial globus pallidus of the basal ganglia and the lateral habenula (LHb) as well as in dopamine and serotonin neurons. Here, I hypothesize that rewarding and aversive experiences require the medial globus pallidus-LHb pathway, and rapid cellular adaptations in LHb to orchestrate dopamine and serotonin systems. To test this my specific aims are: 1 - Anatomical-functional circuit dissection to map LHb inputs from the medial globus pallidus, and LHb outputs to the midbrain using viral-based mapping 2 – Assess the effect of salience (reward, aversion) on the LHb using synaptic physiology and optogenetics and 3 - Causally link LHb activity with behaviours modelling reward/aversion to probe LHb function at the network level using in vivo electrophysiology and optogenetics. I propose to unravel early cellular processes fundamental to “pursue a reward, escape a danger”, which is relevant for encoding rewarding and aversive stimuli in health and neuropsychiatry (i.e. addiction, depression, post-traumatic stress disorders).
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Funding SchemeERC-SG - ERC Starting Grant