Cited by 185Stress Responses and CortisolNeuroscience and Neuropharmacology ResearchNeuropeptides and Animal Physiology

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GABAergic innervation of corticotropin-releasing hormone (CRH)-secreting parvocellular neurons and its plasticity as demonstrated by quantitative immunoelectron microscopy

Miklós, I.H, Kovács, K.J·2002·Neuroscience

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Abstract

GABA has been identified as an important neurotransmitter in stress-related circuitry mediating inhibitory effects on neurosecretory neurons that comprise the central limb of the hypothalamo-pituitary-adrenocortical axis. Using combinations of pre-embedding immunostaining and postembedding immunogold methods at the ultrastructural level, direct synaptic contacts were revealed between GABA-containing terminals and neurosecretory cells that were immunoreactive for corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN). The vast majority of axo-dendritic GABA synapses was symmetric (inhibitory) type, and 46% of all synaptic boutons in the medial parvocellular subdivision of the PVN were immunoreactive to GABA. Using the disector method, an unbiased stereological method on serial ultrathin sections, the total calculated number of synaptic contacts within the medial parvocellular subdivision of the PVN was 55.4 x 10(6)/mm(3). On CRH-positive profiles 20.1 x 10(6) GABAergic synaptic boutons were detected per mm(3) in control, colchicine-treated rats. In the medial parvocellular subdivision, 79% of GABAergic boutons terminated on CRH neurons. Following adrenalectomy, which increases the synthetic and secretory activities of CRH neurons, the number of GABAergic synapses that terminate on CRH-positive profiles was increased by 55%. GABA-containing boutons appeared to be swollen, while the contact surfaces of cellular membranes between GABAergic boutons and CRH-positive profiles were shorter in adrenalectomized animals than in controls. Our data provide ultrastructural evidence for direct inhibitory GABAergic control of stress-related CRH neurons and suggest a pivotal role of GABA-containing inputs in the functional plasticity of parvocellular neurosecretory neurons seen in response to adrenalectomy.

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Additional file 3 of Single-cell morphological characterization of CRH neurons throughout the whole mouse brain
Wang, Y., Hu, P., Shan, Q., Huang, C., Huang, Z., Chen, P., Li, A., Gong, H., & Zhou, J.-N. (2021) · Figshare · doi:10.6084/m9.figshare.14220986
Additional file 1 of Single-cell morphological characterization of CRH neurons throughout the whole mouse brain
Wang, Y., Hu, P., Shan, Q., Huang, C., Huang, Z., Chen, P., Li, A., Gong, H., & Zhou, J.-N. (2021) · Figshare · doi:10.6084/m9.figshare.14220980
Additional file 2 of Single-cell morphological characterization of CRH neurons throughout the whole mouse brain
Wang, Y., Hu, P., Shan, Q., Huang, C., Huang, Z., Chen, P., Li, A., Gong, H., & Zhou, J.-N. (2021) · Figshare · doi:10.6084/m9.figshare.14220983
Additional file 1 of Characterizing dysregulations via cell-cell communications in Alzheimer’s brains using single-cell transcriptomes
Lee, C. Y., Riffle, D., Xiong, Y., Momtaz, N., Lei, Y., Pariser, J. M., Sikdar, D., Hwang, A., Duan, Z., & Zhang, J. (2024) · Figshare · doi:10.6084/m9.figshare.26719791
Additional file 4 of Single-cell morphological characterization of CRH neurons throughout the whole mouse brain
Wang, Y., Hu, P., Shan, Q., Huang, C., Huang, Z., Chen, P., Li, A., Gong, H., & Zhou, J.-N. (2021) · Figshare · doi:10.6084/m9.figshare.14220989
Plasticité structurale du noyau suprachiasmatique associée à la synchronisation photique de l'horloge circadienne
Clemence, G. (2010) · theses.fr (ABES) · doi:10.70675/f4576f1dz0d59z4eb5z8f85zb207fb107180
Study of the role of the lateral habenula in fear conditioning and stress response in rat
Durieux, L. (2021) · theses.fr (ABES) · doi:10.70675/6aef2b06ze4d6z47dezbb31z9f954c98768d
WNK-SPAK-NKCC1/KCC2 pathway disrupts chloride homeostasis and drives hyperactivation of PVN-CRH neurons in essential hypertension
Guo, X., Ma, H., Zhao, Q., Zhang, Y., Yang, P., Zhao, Q., Jia, L., Zhang, L., Guan, Y., Zhang, Y., et al. (2026) · iScience · doi:10.1016/j.isci.2026.116593
A Hypothalamic Inhibitory Circuit Encoding the Scalability of Stress ResponsesPreprint
Cao, Y., Seese, M. H., Jiang, Z., Su, C., Yang, M., Monte, F. H. D., Tong, Q., & Xu, Y. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.30.735593
GABAergic Control of the Hypothalamic–Pituitary–Adrenal (HPA) Axis: Role of Extrasynaptic GABAA Receptors
Maguire, J. L. (2014) · The Receptors · doi:10.1007/978-1-4939-1426-5_12

Authors: Miklós, I. H., & Kovács, K. J.
Affiliations: HUN-REN Institute of Experimental Medicine (HU)
Corresponding author: Kovács, K.J
ORCID: Miklós, I.H
Kovács, K.J
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2002-09
Volume: 113
Issue: 3
Pages: 581-592
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/s0306-4522(02)00147-1
OpenAlex: W2091326035
Cited by: 182
References: 62
Citations by year: 2026: 6 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 11 · 2017: 3 · 2016: 5 · 2015: 10 · 2014: 9 · 2013: 12 · 2012: 7
FWCI: 2.48
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: GABAergic innervation, corticotropin-releasing factor, parvocellular neurons, paraventricular nucleus, hypothalamic-pituitary-adrenal axis, GABAergic synapses, synaptic plasticity, adrenalectomy, stress response, neurosecretory cells, colchicine
MeSH terms: Adrenalectomy, Animals, Corticotropin-Releasing Hormone, gamma-Aminobutyric Acid, Immunohistochemistry, Male, Neuronal Plasticity, Neurons, Paraventricular Hypothalamic Nucleus, Synapses, Microscopy, Immunoelectron, Rats, Wistar, Presynaptic Terminals, Rats

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GABAergic innervation of corticotropin-releasing hormone (CRH)-secreting parvocellular neurons and its plasticity as demonstrated by quantitative immunoelectron microscopy

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