PT - JOURNAL ARTICLE AU - Gian Pietro Serra AU - Adriane Guillaumin AU - Jérome Baufreton AU - François Georges AU - Åsa Wallén-Mackenzie TI - Aversion encoded in the subthalamic nucleus AID - 10.1101/2020.07.09.195610 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.07.09.195610 4099 - http://biorxiv.org/content/early/2020/07/10/2020.07.09.195610.short 4100 - http://biorxiv.org/content/early/2020/07/10/2020.07.09.195610.full AB - Activation of the subthalamic nucleus (STN) is associated with the stopping of ongoing behavior via the basal ganglia. However, we recently observed that optogenetic STN excitation induced a strong jumping/escaping behavior. We hypothesized that STN activation is aversive. To test this, place preference was assessed. Optogenetic excitation of the STN caused potent place aversion. Causality between STN activation and aversion has not been demonstrated previously. The lateral habenula (LHb) is a critical hub for aversion. Optogenetic stimulation of the STN indeed caused firing of LHb neurons, but with delay, suggesting the involvement of a polysynaptic circuit. To unravel a putative pathway, the ventral pallidum (VP) was investigated. VP receives projections from the STN and in turn projects to the LHb. Optogenetic excitation of STN-VP terminals caused firing of VP neurons and induced aversive behavior. This study identifies the STN as critical hub for aversion, potentially mediated via an STN-VP-LHb pathway.Competing Interest StatementThe authors have declared no competing interest.