title: CRF receptor type 2 neurons in the posterior bed nucleus of the stria terminalis critically contribute to stress recovery.
abstract: The bed nucleus of the stria terminalis (BNST) is critical in mediating states of anxiety, and its dysfunction has been linked to stress-related mental disease. Although the anxiety-related role of distinct subregions of the anterior BNST was recently reported, little is known about the contribution of the posterior BNST (pBNST) to the behavioral and neuroendocrine responses to stress. Previously, we observed abnormal expression of corticotropin-releasing factor receptor type 2 (CRFR2) to be associated with post-traumatic stress disorder (PTSD)-like symptoms. Here, we found that CRFR2-expressing neurons within the pBNST send dense inhibitory projections to other stress-related brain regions (for example, the locus coeruleus, medial amygdala and paraventricular nucleus), implicating a prominent role of these neurons in orchestrating the neuroendocrine, autonomic and behavioral response to stressful situations. Local CRFR2 activation by urocortin 3 depolarized the cells, increased the neuronal input resistance and increased firing of action potentials, indicating an enhanced excitability. Furthermore, we showed that CRFR2-expressing neurons within the pBNST are critically involved in the modulation of the behavioral and neuroendocrine response to stress. Optogenetic activation of CRFR2 neurons in the pBNST decreased anxiety, attenuated the neuroendocrine stress response, ameliorated stress-induced anxiety and impaired the fear memory for the stressful event. Moreover, activation following trauma exposure reduced the susceptibility for PTSD-like symptoms. Optogenetic inhibition of pBNST CRFR2 neurons yielded opposite effects. These data indicate the relevance of pBNST activity for adaptive stress recovery.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: M J A G
authors.initials: MJAG
authors.lastname: Henckens
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Printz
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: U
authors.initials: U
authors.lastname: Shamgar
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Dine
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Lebow
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Drori
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kuehne
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kolarz
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Eder
authors.affiliation: Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Deussing
authors.affiliation: Center for Metabolic and Degenerative Diseases, Institute of Molecular Medicine, University of Texas Health Sciences Center, Houston, TX, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Justice
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: O
authors.identifier: http://orcid.org/0000-0003-4228-1448
authors.initials: O
authors.lastname: Yizhar
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.|Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000473:pathology; D004198:Disease Susceptibility / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D012686:Septal Nuclei / Q000378:metabolism* / Q000473:pathology; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism / Q000473:pathology; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D046509:Tissue Culture Techniques; D054832:Urocortins / Q000378:metabolism
chemical_list: C101531:CRF receptor type 2; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C000602668:Ucn3 protein, mouse; D054832:Urocortins