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Local circuit regulation of paraventricular nucleus stress integration
Abstract
Limbic neurocircuits play a central role in regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Limbic influences on adrenocortical hormone secretion are mediated by transynaptic activation or inhibition of hypophysiotrophic neurons in the medial parvocellular paraventricular nucleus (PVN). Projections from the ventral subiculum, prefrontal cortex, medial amygdala, lateral septum, paraventricular thalamus and suprachiasmatic nucleus (SN) terminate in the immediate surround of the PVN, an area heavily populated by GABAergic interneurons. As such, these regions are positioned to modulate paraventricular output via excitation or inhibition of interneuronal projections into the PVN. In addition, the same limbic and diencephalic regions have projections to local PVN-projecting hypothalamic and basal telencephalic nuclei, including the dorsomedial and medial preoptic nuclei and the bed nucleus of the stria terminalis. These regions are involved in both inhibitory and excitatory regulation of the stress axis, indicating that they contain heterogeneous neuronal populations whose relative impact on the PVN is determined by the nature of afferent stimuli. Thus, limbic modulation of the pituitary-adrenocortical system appears to be a multisynaptic process integrated at the level of local PVN-projecting neurocircuits. Local circuits are likely the primary integrators of anticipatory stress responses, and may indeed be the focus of HPA dysfunction seen with aging or affective disease.
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“Because there are no direct hippocampal, prefrontal, or amygdalar connections to the PVN, feedback from these regions are instead relayed via the BNST, lateral septum, and ventromedial hypothalamus (VMH), which are all predominantly GABAergic (Herman et al., 2002(Herman et al., , 2004)).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Herman et al., 2002
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Metadata
- Authors
- Herman, J. P., Tasker, J. G., Ziegler, D. R., & Cullinan, W. E.
- Affiliations
- University of Cincinnati (US)
- Tulane University (US)
- Marquette University (US)
- Corresponding author
- Herman, James P.
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 71
- Issue
- 3
- Pages
- 457-468
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W1265796269
- Cited by
- 274
- References
- 103
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 5 · 2023: 6 · 2022: 11 · 2021: 12 · 2020: 10 · 2019: 7 · 2018: 9 · 2017: 4 · 2016: 10 · 2015: 13 · 2014: 13 · 2013: 15 · 2012: 9
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29ns031187-05, 5r03mh060819-03)
- National Institute of Mental Health (R01 MH56577, MH 60819, R01MH049698, R01 MH11980, R01 MH49698)
- National Institute of Neurological Disorders and Stroke (NS31187)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- paraventricular nucleus, hypothalamic-pituitary-adrenal axis, stress response, GABAergic interneurons, limbic system, ventral subiculum, medial amygdala, suprachiasmatic nucleus, bed nucleus of the stria terminalis, dorsomedial hypothalamus, medial preoptic nucleus, anticipatory stress, aging, mood disorders
- MeSH terms
- Animals, gamma-Aminobutyric Acid, Humans, Nerve Net, Neural Pathways, Paraventricular Hypothalamic Nucleus, Stress, Physiological, Glutamic Acid
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