title: A Basal Forebrain Site Coordinates the Modulation of Endocrine and Behavioral Stress Responses via Divergent Neural Pathways.
abstract: The bed nuclei of the stria terminalis (BST) are critically important for integrating stress-related signals between the limbic forebrain and hypothalamo-pituitary-adrenal (HPA) effector neurons in the paraventricular hypothalamus (PVH). Nevertheless, the circuitry underlying BST control over the stress axis and its role in depression-related behaviors has remained obscure. Utilizing optogenetic approaches in rats, we have identified a novel role for the anteroventral subdivision of BST in the coordinated inhibition of both HPA output and passive coping behaviors during acute inescapable (tail suspension, TS) stress. Follow-up experiments probed axonal pathways emanating from the anteroventral BST which accounted for separable endocrine and behavioral functions subserved by this cell group. The PVH and ventrolateral periaqueductal gray were recipients of GABAergic outputs from the anteroventral BST that were necessary to restrain stress-induced HPA activation and passive coping behavior, respectively, during TS and forced swim tests. In contrast to other BST subdivisions implicated in anxiety-like responses, these results direct attention to the anteroventral BST as a nodal point in a stress-modulatory network for coordinating neuroendocrine and behavioral coping responses, wherein impairment could account for core features of stress-related mood disorders.
  
  
  
  Dysregulation of the neural pathways modulating stress-adaptive behaviors is implicated in stress-related psychiatric illness. While aversive situations activate a network of limbic forebrain regions thought to mediate such changes, little is known about how this information is integrated to orchestrate complex stress responses. Here we identify novel roles for the anteroventral bed nuclei of the stria terminalis in inhibiting both stress hormone output and passive coping behavior via divergent projections to regions of the hypothalamus and midbrain. Inhibition of these projections produced features observed with rodent models of depression, namely stress hormone hypersecretion and increased passive coping behavior, suggesting that dysfunction in these networks may contribute to expression of pathological changes in stress-related disorders.
authors.affiliation: Interdisciplinary Neuroscience Program.
authors.forename: Shane B
authors.identifier: 0000-0003-3425-9726
authors.initials: SB
authors.lastname: Johnson
authors.affiliation: Interdisciplinary Neuroscience Program.
authors.forename: Eric B
authors.identifier: 0000-0001-5351-5073
authors.initials: EB
authors.lastname: Emmons
authors.affiliation: Department of Psychological and Brain Sciences, and.
authors.forename: Rachel M
authors.identifier: 0000-0003-1069-9161
authors.initials: RM
authors.lastname: Anderson
authors.affiliation: Department of Psychological and Brain Sciences, and.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Glanz
authors.affiliation: Department of Psychological and Brain Sciences, and.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Romig-Martin
authors.affiliation: Interdisciplinary Neuroscience Program, Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242.
authors.forename: Nandakumar S
authors.initials: NS
authors.lastname: Narayanan
authors.affiliation: Interdisciplinary Neuroscience Program, Department of Psychological and Brain Sciences, and.
authors.forename: Ryan T
authors.identifier: 0000-0002-1235-0521
authors.initials: RT
authors.lastname: LaLumiere
authors.affiliation: Interdisciplinary Neuroscience Program, Department of Psychological and Brain Sciences, and Jason-radley@uiowa.edu.
authors.forename: Jason J
authors.identifier: 0000-0001-5563-6637
authors.initials: JJ
authors.lastname: Radley
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D066187:Basal Forebrain / Q000378:metabolism*; D000075402:Channelrhodopsins; D003345:Corticosterone / Q000378:metabolism; D004703:Endocrine System / Q000503:physiopathology*; D046352:Freezing Reaction, Cataleptic; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D062308:Optogenetics; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000473:pathology*; D016704:Synapsins / Q000378:metabolism; D014161:Transduction, Genetic; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism
chemical_list: D000075402:Channelrhodopsins; D008164:Luminescent Proteins; D016704:Synapsins; D050496:Vesicular Glutamate Transport Proteins; D000324:Adrenocorticotropic Hormone; D005968:Glutamate Decarboxylase; D003345:Corticosterone
keywords: HPA; bed nuclei of the stria terminalis; behavioral coping; corticosterone; paraventricular hypothalamus; periaqueductal gray area