Library Subscription: Guest
Begell Digital Portal Begell Digital Library eBooks Journals References & Proceedings Research Collections
Critical Reviews™ in Neurobiology
SJR: 0.121

ISSN Print: 0892-0915
ISSN Online: 2375-0014

Archives: Volume 10, 1996 to Volume 20, 2008

Critical Reviews™ in Neurobiology

DOI: 10.1615/CritRevNeurobiol.v10.i3-4.50
pages 371-394

Neuronal Circuit Regulation of the Hypothalamo-Pituitary-Adrenocortical Stress Axis

James P. Herman
Department of Anatomy and Neurobiology, University of Kentucky School of Medicine, 800 Rose Street, Lexington, KY 40536-0084
Chantai M.-F. Prewitt
Department of Anatomy and Neurobiology, University of Kentucky School of Medicine, 800 Rose Street, Lexington, KY 40536-0084
William E. Cullinan
Department of Basic Health Sciences, Marquette University, Milwaukee, Wl 53233


The hypothalamo-pituitary-adrenocortical (HPA) axis is the primary modulator of the adrenal glucocorticoid stress response. Activation of this axis occurs by way of a discrete set of neurons in the hypothalamic paraventricular nucleus (PVN). The PVN neuron appears to be affected by multiple sources, including (1) brainstem aminergic/peptidergic afferents; (2) blood-borne information; (3) indirect input from limbic system-associated regions, including the prefrontal cortex, hippocampus, and amygdala; and (4) local-circuit interactions with the preoptic-hypothalamic continuum. Analysis of the literature suggests that different classes of stressor employ different stress circuits. Severe physiologic ("systemic") stress appears to trigger brainstem/circumventricular organ systems that project directly to the paraventricular nucleus. In contrast, stressors requiring interpretation with respect to previous experience ("processive" stressors) reach the PVN by way of multisynaptic limbic pathways. Limbic regions mediating processive stress responses appear to have bisynaptic connections with the PVN, forming intervening connections with preoptic/hypothalamic GABAergic neurons. Stressors of the latter category may thus require interaction with homeostatic information prior to promoting an HPA response. The HPA stress response thus appears to be a product of both the physiologic importance of the stimulus and the specific pathways a given stimulus excites.

Articles with similar content:

Scavenger Receptor-A (CD204): A Two-Edged Sword in Health and Disease
Critical Reviews™ in Immunology, Vol.34, 2014, issue 3
Jim L. Kelley, John B. Schweitzer, Tammy R. Ozment, Chuanfu Li, David L. Williams
Immune Functions of Proteinase 3
Critical Reviews™ in Immunology, Vol.25, 2005, issue 5
Shunji Sugawara
A Functional Neuroanatomy of Anxiety and Fear: Implications for the Pathophysiology and Treatment of Anxiety Disorders
Critical Reviews™ in Neurobiology, Vol.10, 1996, issue 3-4
Ariel Deutch, Dennis S. Charney
PAX Proteins and Fables of Their Reconstruction
Critical Reviews™ in Eukaryotic Gene Expression, Vol.22, 2012, issue 2
Darrell Alan Underhill
Functional Relationship Among Medial Prefrontal Cortex, Nucleus Accumbens, and Ventral Tegmental Area in Locomotion and Reward
Critical Reviews™ in Neurobiology, Vol.14, 2000, issue 2
Werner J. Schmidt, Thomas M. Tzschentke