Faculty Collaboration Database

Functional role of local GABAergic influences on the HPA axis. Brain Struct Funct 2008 Sep;213(1-2):63-72

Date

08/13/2008

Pubmed ID

18696110

DOI

10.1007/s00429-008-0192-2

Scopus ID

2-s2.0-50249092178 (requires institutional sign-in at Scopus site)   206 Citations

Abstract

Neuronatomical and pharmacological studies have established GABA-mediated inhibition of the HPA axis at the level of the PVN. The origin of this innervation is a series of local hypothalamic and adjacent forebrain regions that project to stress-integrative hypophysiotropic CRH neurons. While a role in tonic inhibition of the stress axis is likely, this system of inhibitory loci is also capable of producing a dynamic braking capacity in the context of the neuroendocrine stress response. The latter function is mediated in large part by glutamatergic forebrain afferents that increase GABA release at the level of the PVN. In addition, this local GABA system can be inhibited by upstream GABAergic projection neurons, producing activation of the HPA axis via removal of GABAergic tone. This PVN projecting GABA network interfaces with a wide range of homeostatic mechanisms, and is capable of biochemical plasticity in response to chronic stress. Collectively, the elements of this system provide for exquisite control of neuroendocrine activation in the face of stressful stimuli, and loss of this regulatory capacity may underlie many stress-related disorders.

Author List

Cullinan WE, Ziegler DR, Herman JP

Author

William E. Cullinan PhD Adjunct Associate Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Corticotropin-Releasing Hormone
Humans
Hypothalamo-Hypophyseal System
Neural Pathways
Neurons
Paraventricular Hypothalamic Nucleus
Pituitary-Adrenal System
gamma-Aminobutyric Acid