A Basal Forebrain Site Coordinates the Modulation of Endocrine and Behavioral Stress Responses via Divergent Neural Pathways.
UNLABELLED
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.


SIGNIFICANCE STATEMENT
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.
['Johnson|Shane B|SB|0000-0003-3425-9726', 'Emmons|Eric B|EB|0000-0001-5351-5073', 'Anderson|Rachel M|RM|0000-0003-1069-9161', 'Glanz|Ryan M|RM|', 'Romig-Martin|Sara A|SA|', 'Narayanan|Nandakumar S|NS|', 'LaLumiere|Ryan T|RT|0000-0002-1235-0521', 'Radley|Jason J|JJ|0000-0001-5563-6637']
D000324:Adrenocorticotropic Hormone D000818:Animals D066187:Basal Forebrain D000075402:Channelrhodopsins D003345:Corticosterone D004703:Endocrine System D046352:Freezing Reaction, Cataleptic D005968:Glutamate Decarboxylase D008164:Luminescent Proteins D051379:Mice D009434:Neural Pathways D009474:Neurons D062308:Optogenetics D010286:Paraventricular Hypothalamic Nucleus D051381:Rats D017207:Rats, Sprague-Dawley D013315:Stress, Psychological D016704:Synapsins D014161:Transduction, Genetic D050496:Vesicular Glutamate Transport Proteins
bed nuclei of the stria terminalis HPA paraventricular hypothalamus behavioral coping corticosterone periaqueductal gray area