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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #367612
Title: Defensive behaviors driven by a hypothalamic-ventral midbrain circuit

Author
item MANGIERI, LEANDRA - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER
item JIANG, ZHIYING - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER
item LU, YUNGANG - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER
item XU, YUANZHONG - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER
item CASSIDY, RYAN - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER
item JUSTICE, NICHOLAS - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER
item XU, YONG - CHILDREN'S NUTRITION RESEARCH CENTER (CNRC)
item ARENKIEL, BENJIAMIN - BAYLOR COLLEGE OF MEDICINE
item TONG, QINGCHUN - UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER

Submitted to: eNeuro
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/17/2019
Publication Date: 7/22/2019
Citation: Mangieri, L., Jiang, Z., Lu, Y., Xu, Y., Cassidy, R.M., Justice, N., Xu, Y., Arenkiel, B., Tong, Q. 2019. Defensive behaviors driven by a hypothalamic-ventral midbrain circuit. eNeuro. 6(4):1-19. https://doi.org/10.1523/ENEURO.0156-19.2019.
DOI: https://doi.org/10.1523/ENEURO.0156-19.2019

Interpretive Summary: Defensive behavior is essential for survival. However, the brain mechanisms for this behavior remain unclear. Here we discovered a novel neural circuit within the brain that regulates the defensive behavior of mice. Defensive behaviors such as shelter-seeking and escape represent innate behaviors that are crucial for survival. Findings from this study help researchers to better understand coping strategies in people which may involve social avoidance and behavioral compulsions which may include overeating.

Technical Abstract: 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 nondopaminergic 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.