Cited by 1,244Neuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors StudyReceptor Mechanisms and Signaling

GABA A ‐receptor heterogeneity in the adult rat brain: Differential regional and cellular distribution of seven major subunits

Fritschy, Jean‐Marc, Mohler, Hanns·1995·Journal of Comparative Neurology

Abstract

GABAA-receptors display an extensive structural heterogeneity based on the differential assembly of a family of at least 15 subunits (alpha 1-6, beta 1-3, gamma 1-3, delta, rho 1-2) into distinct heteromeric receptor complexes. The subunit composition of receptor subtypes is expected to determine their physiological properties and pharmacological profiles, thereby contributing to flexibility in signal transduction and allosteric modulation. In heterologous expression systems, functional receptors require a combination of alpha-, beta-, and gamma-subunit variants, the gamma 2-subunit being essential to convey a classical benzodiazepine site to the receptor. The subunit composition and stoichiometry of native GABAA-receptor subtypes remain unknown. The aim of this study was to identify immunohistochemically the main subunit combinations expressed in the adult rat brain and to allocate them to identified neurons. The regional and cellular distribution of seven major subunits (alpha 1, alpha 2, alpha 3, alpha 5, beta 2,3, gamma 2, delta) was visualized by immunoperoxidase staining with subunit-specific antibodies (the beta 2- and beta 3-subunits were covisualized with the monoclonal antibody bd-17). Putative receptor subtypes were identified on the basis of colocalization of subunits within individual neurons, as analyzed by confocal laser microscopy in double- and triple-immunofluorescence staining experiments. The results reveal an extraordinary heterogeneity in the distribution of GABAA-receptor subunits, as evidenced by abrupt changes in immunoreactivity along well-defined cytoarchitectonic boundaries and by pronounced differences in the cellular distribution of subunits among various types of neurons. Thus, functionally and morphologically diverse neurons were characterized by a distinct GABAA-receptor subunit repertoire. The multiple staining experiments identified 12 subunit combinations in defined neurons. The most prevalent combination was the triplet alpha 1/beta 2,3/gamma 2, detected in numerous cell types throughout the brain. An additional subunit (alpha 2, alpha 3, or delta) sometimes was associated with this triplet, pointing to the existence of receptors containing four subunits. The triplets alpha 2/beta 2,3/gamma 2, alpha 3/beta 2,3/gamma 2, and alpha 5/beta 2,3/gamma 2 were also identified in discrete cell populations. The prevalence of these seven combinations suggest that they represent major GABAA-receptor subtypes. Five combinations also apparently lacked the beta 2,3-subunits, including one devoid of gamma 2-subunit (alpha 1/alpha 2/gamma 2, alpha 2/gamma 2, alpha 3/gamma 2, alpha 2/alpha 3/gamma 2, alpha 2/alpha 5/delta).(ABSTRACT TRUNCATED AT 400 WORDS)

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Crossref · 10.1002/cne.903590111

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  • α2GABAARs are densely expressed in the central amygdala.

    “α2-GABAARs are densely expressed in the central amygdala [35, 36, 40], but their precise cellular location and function are still unknown.”

    From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [35]

  • α5GABAARs are expressed at negligible levels in the CeA.

    “This finding is striking, as α5GABAARs are expressed at negligible levels in the CeA [35, 36]”

    From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [35]

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Authors
Fritschy, J., & Mohler, H.
Affiliations
University of Zurich (CH)
Corresponding author
Fritschy, Jean‐Marc
Venue
Journal of Comparative Neurology
Publisher
Wiley
Published
1995-08-14
Volume
359
Issue
1
Pages
154-194
ISSN
  • 0021-9967 (ISSN-L)
  • 1096-9861
OpenAlex
W2039738625
Cited by
1,244
References
125
Citations by year
2026: 17 · 2025: 11 · 2024: 24 · 2023: 15 · 2022: 24 · 2021: 35 · 2020: 28 · 2019: 19 · 2018: 33 · 2017: 31 · 2016: 33 · 2015: 24 · 2014: 46 · 2013: 28 · 2012: 45
FWCI
14.52
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Comparative Neurology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
GABAA receptor, benzodiazepine binding site, subunit stoichiometry, regional distribution, neuronal cell types, GABAergic interneurons, GABAergic projection neurons
MeSH terms
Amygdala, Animals, Basal Ganglia, Brain Chemistry, Brain Stem, Cerebellum, Cerebral Cortex, Fluorescent Antibody Technique, Hypothalamus, Immunohistochemistry, Male, Neurons, Olfactory Bulb, Receptors, GABA-A, Subcellular Fractions, Superior Colliculi, Thalamus, Prosencephalon, Rats, Sprague-Dawley, Rats

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