A discrete GABAergic relay mediates medial prefrontal cortical inhibition of the neuroendocrine stress response

Jason J Radley; Kristin L Gosselink; Paul E Sawchenko

doi:10.1523/JNEUROSCI.5924-08.2009

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A discrete GABAergic relay mediates medial prefrontal cortical inhibition of the neuroendocrine stress response

Journal article

Open access

Peer reviewed

A discrete GABAergic relay mediates medial prefrontal cortical inhibition of the neuroendocrine stress response

Jason J Radley, Kristin L Gosselink and Paul E Sawchenko

The Journal of neuroscience, Vol.29(22), pp.7330-7340

06/03/2009

DOI: 10.1523/JNEUROSCI.5924-08.2009

PMCID: PMC2743123

PMID: 19494154

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Abstract

Complementing its roles in cognitive and affective information processing, the medial prefrontal cortex (mPFC) is a nodal point of a limbic forebrain circuit that modulates stress-related homeostatic mechanisms, including the hypothalamic-pituitary-adrenal (HPA) axis. mPFC influences on HPA output are predominantly inhibitory and emanate from the prelimbic and/or dorsal anterior cingulate cortical fields (PL and ACd, respectively). mPFC projections do not target HPA effector neurons in the paraventricular hypothalamic nucleus (PVH) directly, distributing instead to nearby forebrain regions, including some that house GABAergic neurons implicated in inhibitory PVH control. To identify pathway(s) subserving HPA-inhibitory mPFC influences, an initial screen for sources of GABAergic input to PVH whose sensitivity to an acute emotional (restraint) stress was diminished by PL/ACd lesions identified a discrete region of the anterior bed nucleus of the stria terminalis (aBST) as a candidate for fulfilling this role. Anatomical tracing experiments confirmed projections from PL (but not ACd) to implicated aBST cell groups, and from these to PVH. Finally, selective immunotoxin-mediated ablation of GABAergic aBST neurons recapitulated the effects of PL/ACd lesions on acute stress-induced activation of HPA output. The identification of a proximate mediator of HPA-inhibitory limbic influences provides a framework for clarifying how inhibitory neural and hormonal controls of HPA output are integrated, adaptations of the axis to chronic stress are effected, and how endocrine abnormalities may contribute to stress-related psychiatric illnesses in which mPFC dysfunction is implicated.

Ibotenic Acid - toxicity

gamma-Aminobutyric Acid - metabolism

Male

RNA, Messenger - metabolism

Neural Inhibition - physiology

Paraventricular Hypothalamic Nucleus - cytology

GABA Plasma Membrane Transport Proteins - metabolism

Phytohemagglutinins - pharmacology

Neurons - physiology

Biotin - metabolism

Corticotropin-Releasing Hormone - genetics

Neurons - drug effects

Dextrans - metabolism

Oncogene Proteins v-fos - metabolism

Stilbamidines - metabolism

Rats

Corticotropin-Releasing Hormone - blood

Glutamate Decarboxylase - genetics

Prefrontal Cortex - cytology

Rats, Sprague-Dawley

Corticotropin-Releasing Hormone - metabolism

Gene Expression Regulation - drug effects

GABA Plasma Membrane Transport Proteins - genetics

Animals

Excitatory Amino Acid Agonists - toxicity

Analysis of Variance

Prefrontal Cortex - injuries

Paraventricular Hypothalamic Nucleus - metabolism

Glutamate Decarboxylase - metabolism

Neural Inhibition - drug effects

Prefrontal Cortex - physiology

Biotin - analogs & derivatives

Stress, Psychological - physiopathology

Details

Title: Subtitle: A discrete GABAergic relay mediates medial prefrontal cortical inhibition of the neuroendocrine stress response
Creators: Jason J Radley - Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies and Clayton Medical Research Foundation, La Jolla, California 92037, USA. radley@salk.edu
Kristin L Gosselink
Paul E Sawchenko
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.29(22), pp.7330-7340
Publisher: United States
DOI: 10.1523/JNEUROSCI.5924-08.2009
PMID: 19494154
PMCID: PMC2743123
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: P01 DK026741-290012 / NIDDK NIH HHS P01 DK026741 / NIDDK NIH HHS DK-26741 / NIDDK NIH HHS
Language: English
Date published: 06/03/2009
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute
Record Identifier: 9984070793702771

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