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The Journal of Neuroscience, February 21, 2007, 27(8):2025-2034; doi:10.1523/JNEUROSCI.4301-06.2007

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Behavioral/Systems/Cognitive
Bed Nucleus of the Stria Terminalis Subregions Differentially Regulate Hypothalamic–Pituitary–Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

Dennis C. Choi,^1,2 Amy R. Furay,^1,2 Nathan K. Evanson,^1,2 Michelle M. Ostrander,² Yvonne M. Ulrich-Lai,² and James P. Herman^1,2,3

¹Neuroscience Program and Departments of ²Psychiatry and ³Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267

Correspondence should be addressed to Dennis C. Choi, University of Cincinnati, Psychiatry North, Building E, 2nd Floor, 2170 East Galbraith Road, Cincinnati, OH 45237-0506. Email: choidc{at}ucmail.uc.edu

Limbic and cortical neurocircuits profoundly influence hypothalamic–pituitary–adrenal (HPA) axis responses to stress yet have little or no direct projections to the hypothalamic paraventricular nucleus (PVN). Numerous lines of evidence suggest that the bed nucleus of the stria terminalis (BST) is well positioned to relay limbic information to the PVN. The BST comprises multiple anatomically distinct nuclei, of which some are known to receive direct limbic and/or cortical input and to heavily innervate the PVN. Our studies test the hypothesis that subregions of the BST differentially regulate HPA axis responses to acute stress. Male Sprague Dawley rats received bilateral ibotenate lesions, targeting either the principal nucleus in the posterior BST or the dorsomedial/fusiform nuclei in the anteroventral BST. Posterior BST lesions elevated plasma ACTH and corticosterone in response to acute restraint stress, increased stress-induced PVN c-fos mRNA, and elevated PVN corticotropin-releasing hormone (CRH) and parvocellular arginine vasopressin (AVP) mRNA expression relative to sham-lesion animals. In contrast, anterior BST lesions attenuated the plasma corticosterone response and decreased c-fos mRNA induction in the PVN but did not affect CRH and parvocellular AVP mRNA expression in the PVN. These data suggest that posterior BST nuclei are involved in inhibition of the HPA axis, whereas the anteroventral BST nuclei are involved in HPA axis excitation. The results indicate that the BST contains functional subdomains that play different roles in integrating and processing limbic information in response to stress and further suggest that excitatory as well as inhibitory limbic information is funneled through these important cell groups.

Key words: BST; corticotropin-releasing hormone; vasopressin; paraventricular nucleus of the hypothalamus; corticosterone; ACTH

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Received Oct. 2, 2006; revised Jan. 19, 2007; accepted Jan. 19, 2007.

Correspondence should be addressed to Dennis C. Choi, University of Cincinnati, Psychiatry North, Building E, 2nd Floor, 2170 East Galbraith Road, Cincinnati, OH 45237-0506. Email: choidc{at}ucmail.uc.edu

This article has been cited by other articles:

				B. Bingham and V. Viau Neonatal Gonadectomy and Adult Testosterone Replacement Suggest an Involvement of Limbic Arginine Vasopressin and Androgen Receptors in the Organization of the Hypothalamic-Pituitary-Adrenal Axis Endocrinology, July 1, 2008; 149(7): 3581 - 3591. [Abstract] [Full Text] [PDF]

				J. J. Radley, B. Williams, and P. E. Sawchenko Noradrenergic Innervation of the Dorsal Medial Prefrontal Cortex Modulates Hypothalamo-Pituitary-Adrenal Responses to Acute Emotional Stress J. Neurosci., May 28, 2008; 28(22): 5806 - 5816. [Abstract] [Full Text] [PDF]

				D. C. Choi, N. K. Evanson, A. R. Furay, Y. M. Ulrich-Lai, M. M. Ostrander, and J. P. Herman The Anteroventral Bed Nucleus of the Stria Terminalis Differentially Regulates Hypothalamic-Pituitary-Adrenocortical Axis Responses to Acute and Chronic Stress Endocrinology, February 1, 2008; 149(2): 818 - 826. [Abstract] [Full Text] [PDF]

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