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 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.
Footnotes
The authors declare no competing financial interests.
This work was supported by Department of Health and Human Services (HHS) National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grants R01DK114279 (to Q.T.); R01DK109934 (to B.R.A. and Q.T.); R01DK117281, R01DK101379, and P01DK113954 (to Yong Xu); the HHS NIH National Institute of Neurological Disorders and Stroke Grant R21NS108091 (to Q.T.); the HHS NIH National Institute on Drug Abuse Grant 5F31DA041703 (to L.R.M.); and the HHS NIH National Institute on Minority Health and Health Disparities Grant U54 HD083092. R.M.C. was supported by the TL1 Training Grant 4TL1TR000369 (Center for Clinical and Translational Sciences, The University of Texas Health Science Center at Houston).
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.