RT Journal Article SR Electronic T1 Defensive Behaviors Driven by a Hypothalamic-Ventral Midbrain Circuit JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0156-19.2019 DO 10.1523/ENEURO.0156-19.2019 VO 6 IS 4 A1 Mangieri, Leandra R. A1 Jiang, Zhiying A1 Lu, Yungang A1 Xu, Yuanzhong A1 Cassidy, Ryan M. A1 Justice, Nicholas A1 Xu, Yong A1 Arenkiel, Benjamin R. A1 Tong, Qingchun YR 2019 UL http://www.eneuro.org/content/6/4/ENEURO.0156-19.2019.abstract AB The paraventricular hypothalamus (PVH) regulates stress, feeding behaviors and other homeostatic processes, but whether PVH also drives defensive states remains unknown. Here we showed that photostimulation of PVH neurons in mice elicited escape jumping, a typical defensive behavior. We mapped PVH outputs that densely terminate in the ventral midbrain (vMB) area, and found that activation of the PVH→vMB circuit produced profound defensive behavioral changes, including escape jumping, hiding, hyperlocomotion, and learned aversion. Electrophysiological recordings showed excitatory postsynaptic input onto vMB neurons via PVH fiber activation, and in vivo studies demonstrated that glutamate transmission from PVH→vMB was required for the evoked behavioral responses. Photostimulation of PVH→vMB fibers induced cFos expression mainly in non-dopaminergic neurons. Using a dual optogenetic-chemogenetic strategy, we further revealed that escape jumping and hiding were partially contributed by the activation of midbrain glutamatergic neurons. Taken together, our work unveils a hypothalamic-vMB circuit that encodes defensive properties, which may be implicated in stress-induced defensive responses.