Brain Structure and Function

, 213:63

Functional role of local GABAergic influences on the HPA axis

  • William E. Cullinan
  • Dana R. Ziegler
  • James P. Herman
Review

DOI: 10.1007/s00429-008-0192-2

Cite this article as:
Cullinan, W.E., Ziegler, D.R. & Herman, J.P. Brain Struct Funct (2008) 213: 63. doi:10.1007/s00429-008-0192-2

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.

Keywords

GABA Stress axis Hypothalamus Glucocorticoids Neuroanatomy Pharmacology 

Abbreviations

3V

Third ventricle

5-HT

5-Hydroxytryptamine (serotonin)

IX

Cranial nerve IX

X

Cranial nerve X

A1

Brainstem noradrenergic area, A1

A2

Brainstem noradrenergic area, A2

ac

Anterior commissure

aCSF

Artificial cerebrospinal fluid

ACTH

Adrenocorticotropic hormone

AHN

Anterior hypothalamic nucleus

Arc

Arcuate nucleus

B6

Brainstem serotoninergic area, B6

B7

Brainstem serotoninergic area, B7

B8

Brainstem serotoninergic area, B8

BNST

Bed nucleus of the stria terminalis

C1

Brainstem adrenergic area, C1

C2

Brainstem adrenergic area, C2

C3

Brainstem adrenergic areas, C3

CeA

Central amygdaloid nucleus

CG

Central grey

CV

Circumventricular organs

DMH

Dorsomedial hypothalamic nucleus

f

Fornix

GLP-1

Glucagon-like peptide 1

Glu

Glutamate

HDB

Horizontal limb, diagonal band

ic

Internal capsule

LC

Locus coeruleus

LDTg

Laterodorsal tegmental area

LH

Lateral hypothalamic area

LPB

Lateral parabrachial nucleus

LPO

Lateral preoptic area

LS

Lateral septal nucleus

MeA

Medial amygdaloid nucleus

MnPO

Median preoptic nucleus

mp

Medial parvocellular PVN

MP

Medial preoptic nucleus

MPA

Medial preoptic area

mPFC

Medial prefrontal cortex

mt

Mammillothalamic tract

Musc

Muscimol

NE

Norepinephrine

NTS

Nucleus of the solitary tract

OVLT

Organum vasculosum, lamina terminalis

ot

Optic tract

PBN

Parabrachial Nucleus

PH

Posterior hypothalamic area

pm

Posterior magnocellular PVN

PMV

Premammillary nucleus, ventral

PPn

Pedunculopontine nucleus

PVN

Paraventricular hypothalamic nucleus

PS

Parastrial nucleus

Rt

Reticular thalamic nucleus

SFO

Subfornical organ

STh

Subthalamic nucleus

VM

Ventromedial hypothalamic nucleus

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • William E. Cullinan
    • 1
  • Dana R. Ziegler
    • 1
  • James P. Herman
    • 2
  1. 1.Department of Biomedical Sciences, College of Health SciencesMarquette UniversityMilwaukeeUSA
  2. 2.Department of Psychiatry, School of MedicineUniversity of CincinnatiCincinnatiUSA