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Functional role of local GABAergic influences on the HPA axis

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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.

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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

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Authors and Affiliations

  1. Department of Biomedical Sciences, College of Health Sciences, Marquette University, Milwaukee, WI, 53201-1881, USA

    William E. Cullinan & Dana R. Ziegler

  2. Department of Psychiatry, School of Medicine, University of Cincinnati, Cincinnati, OH, 45267-0559, USA

    James P. Herman

Authors
  1. William E. Cullinan
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  2. Dana R. Ziegler
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  3. James P. Herman
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Correspondence to William E. Cullinan.

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Cullinan, W.E., Ziegler, D.R. & Herman, J.P. Functional role of local GABAergic influences on the HPA axis. Brain Struct Funct 213, 63–72 (2008). https://doi.org/10.1007/s00429-008-0192-2

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  • DOI: https://doi.org/10.1007/s00429-008-0192-2

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