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Cited by 153Stress Responses and CortisolNeuropeptides and Animal PhysiologyNeuroscience and Neuropharmacology Research

Synaptic regulation of the hypothalamic–pituitary–adrenal axis and its modulation by glucocorticoids and stress

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Levy, Benjamin H., Tasker, Jeffrey G.·2012·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2012.00024PMC PMC3349941
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Abstract

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in a range of affective and stress-related disorders. The regulatory systems that control HPA activity are subject to modulation by environmental influences, and stressful life events or circumstances can promote subsequent HPA dysregulation. The brain is a major regulator of the HPA axis, and stress-induced plasticity of the neural circuitry involved in HPA regulation might constitute an etiological link between stress and the development of HPA dysregulation. This review focuses on the synaptic regulation of neuroendocrine corticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus, which are the cells through which the brain predominantly exerts its influence on the HPA axis. CRH neuronal activity is largely orchestrated by three neurotransmitters: GABA, glutamate, and norepinephrine. We discuss our current understanding of the neural circuitry through which these neurotransmitters regulate CRH cell activity, as well as the plastic changes in this circuitry induced by acute and chronic stress and the resultant changes in HPA function.

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  • Noradrenergic inputs originating in the brainstem act on peri- and intra-paraventricular GABAergic and glutamatergic interneurons to regulate CRH release.

    “Noradrenergic inputs originating in the brainstem act on peri- and intra-paraventricular GABAergic and glutamatergic interneurons to regulate CRH release.”

    From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [110]

    The Figure 2 caption and NOREPINEPHRINE INPUTS section say brainstem noradrenergic inputs modulate GABA and glutamate inputs to PVN CRH neurons. The GABA INPUTS and GLUTAMATE INPUTS sections identify peri- and intra-PVN local circuits. However, the paper describes noradrenergic action on local glutamatergic circuits as preliminary and regulates CRH neuronal activity rather than directly establishing the claimed pathway to CRH release. Page numbers are unavailable in our copy. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • CRH neurons in the hypothalamic paraventricular nucleus require tight regulation predominantly exerted by GABA, glutamate, and norepinephrine.

    “On the HPA axis side, the CRH neurons in the hypothalamic paraventricular nucleus require a tight regulation predominantly exerted by three neurotransmitters: GABA, glutamate, and norepinephrine [108–110].”

    From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [110]

  • Norepinephrine both suppresses and enhances GABAergic inhibition, whereas its excitatory effect on the HPA axis is mainly due to facilitation of glutamate release onto CRH neurons.

    “Norepinephrine both suppresses and enhances GABAergic inhibition, whereas its excitatory effect on the HPA axis is mainly due to a facilitation of glutamate release onto CRH neurons [110].”

    From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [110]

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Cited by

Sorted by citations

Authors
Levy, B. H., & Tasker, J. G.
Affiliations
Tulane University (US)
Corresponding author
Tasker, Jeffrey G.
ORCID
Tasker, Jeffrey G.
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2012
Volume
6
Pages
24-24
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2012.00024
PMC
PMC3349941
OpenAlex
W2145691687
Cited by
153
References
10
Citations by year
2026: 9 · 2025: 11 · 2024: 13 · 2023: 8 · 2022: 12 · 2021: 11 · 2020: 15 · 2019: 7 · 2018: 4 · 2017: 6 · 2016: 7 · 2015: 14 · 2014: 17 · 2013: 16 · 2012: 2
FWCI
6.56
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
hypothalamic-pituitary-adrenal axis, corticotropin-releasing hormone neurons, paraventricular nucleus, synaptic regulation, glucocorticoids, stress, HPA axis dysregulation, GABA, glutamate, norepinephrine, neuroplasticity, stress-related disorders

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