Excitatory SST neurons in the medial paralemniscal nucleus control repetitive self and encode reward

The use of body-focused repetitive behaviors (BFRBs) is conceptualized as a means of coping with stress. However, the neurological mechanism by which repetitive behaviors affect anxiety regulation is unclear. Here, we identify that the excitatory somatostatin-positive neurons in the medial paralemniscal nucleus (MPLSST neurons) in mice promote self-grooming and encode reward. MPLSST neurons display prominent grooming-related neuronal activity. Loss of function of MPLSST neurons impairs both self-grooming and post-stress anxiety alleviation. Activation of MPLSST neurons is rewarding and sufficient to drive reinforce-ment by activating dopamine (DA) neurons in the ventral tegmental area (VTA) and eliciting dopamine release. The neuropeptide SST facilitates the rewarding impact of MPLSST neurons. MPLSST neuron-mediated self -grooming is triggered by the input from the central amygdala (CeA). Our study reveals a dual role of CeA-MPLSST-VTADA circuit in self-grooming and post-stress anxiety regulation and conceptualizes MPLSST neu-rons as an interface linking the stress and reward systems in mice.