GABAA receptors: immunocytochemical distribution of 13 subunits in the adult rat brain

Pirker, Susanne; Schwarzer, Christoph; Wieselthaler, Anna; Sieghart, Werner; Sperk, Günther

doi:10.1016/s0306-4522(00)00442-5

Cited by 1,210 publications

(1,292 citation statements)

References 96 publications

Supporting

130

Mentioning

1,122

Contrasting

Unclassified

Order By: Relevance

“…When using furosemide, which is a selective blocker of the latter, 28 we observed a significantly stronger suppression of IPSCs in neurons from tg than from wt mice (Figure 6c). Since a6-containing GABA A Rs are not expressed in hippocampus 29 and are much more sensitive to furosemide than a4GABA A Rs (IC 50 6 vs 162 mM), 28 the effect of 0.6 mM furosemide in dnActRIB hippocampi can be best explained by assuming a more pronounced contribution of a4GABA A Rs to the IPSC. In addition to potentiating IPSCs, diazepam has been reported to augment the small tonic GABA current in CA1 pyramidal cells.…”

Section: Diazepam Response Is Attenuated In Dnactrib Hippocampusmentioning

confidence: 99%

Activin tunes GABAergic neurotransmission and modulates anxiety-like behavior

Zheng

Adelsberger²,

et al. 2008

Mol Psychiatry

View full text Add to dashboard Cite

Activin, a member of the transforming growth factor-b superfamily, affords neuroprotection in acute brain injury, but its physiological functions in normal adult brain are largely unknown. Using transgenic (tg) mice expressing a dominant-negative activin receptor mutant under the control of the CaMKIIa promoter in forebrain neurons, we identified activin as a key regulator of c-aminobutyric acid (GABA)ergic synapses and anxiety-like behavior. In the open field, wildtype (wt) and tg mice did not differ in spontaneous locomotion and exploration behavior. However, tg mice visited inner fields significantly more often than wt mice. In the light-dark exploration test, tg mice made more exits, spent significantly more time on a well-lit elevated bar and went farther away from the dark box as compared to wt mice. In addition, the anxiolytic effect of diazepam was abrogated in tg mice. Thus the disruption of activin receptor signaling produced a low-anxiety phenotype that failed to respond to benzodiazepines. In whole-cell recordings from hippocampal pyramidal cells, enhanced spontaneous GABA release, increased GABA tonus, reduced benzodiazepine sensitivity and augmented GABA B receptor function emerged as likely substrates of the low-anxiety phenotype. These data provide strong evidence that activin influences pre-and postsynaptic components of GABAergic synapses in a highly synergistic fashion. Given the crucial role of GABAergic neurotransmission in emotional states, anxiety and depression, dysfunctions of activin receptor signaling could be involved in affective disorders: and drugs affecting this pathway might show promise for psychopharmacological treatment.

show abstract

Section: Diazepam Response Is Attenuated In Dnactrib Hippocampusmentioning

confidence: 99%

Activin tunes GABAergic neurotransmission and modulates anxiety-like behavior

Zheng

Adelsberger²,

et al. 2008

Mol Psychiatry

View full text Add to dashboard Cite

show abstract

“…In the mPOA and the SON, β 2/3 subunits are expressed at notably higher levels than is the β 1 subunit, (Wisden et al, 1992;Fritschy and Mohler, 1995;Fénelon et al, 1995;Herbison and Fénelon, 1995). Delta subunit mRNA subunit expression is undetectable in the hypothalamus (Wisden et al, 2002), but while Fritschy and Mohler (1995) report no detectable level of δ subunit immunoreactivity throughout the mPOA/ hypothalamus, Pirker et al (2000) describe expression of α 5 , β 1 and δ subunits on SON perikarya and α 1 , α 2 , and β 1-3 subunit immunoreactivities on dendritic networks in this region. As is characteristic of most of the brain, expression of the γ 2 subunit predominates in the SON/ PVN Fénelon and Herbison, 1996b).…”

Section: Subunit Expression In the Hypothalamus/basal Forebrainmentioning

confidence: 99%

“…Thus, it is tempting to postulate that allopregnanolone modulation of these extrasynaptic, rather than synaptic, conductances may be the critical factor in mediating the changes in oxytocin neuronal firing that occur during late pregnancy and parturition. Delta-containing receptors are known to give rise to most tonic, extrasynaptic conductances in other brain regions, however, given that δ subunit expression in the hypothalamus/basal forebrain is debatable (Fritschy and Mohler, 1995;Pirker et al, 2000) and expression of ε in this brain region is marked (Whiting et al, 1997;Sinkkonen et al, 2000;McIntyre et al, 2002), most notably in the GnRH neurons (Moragues et al, 2003), an intriguing possibility is that ε-containing receptors may play a comparable role in regulating tonic GABAergic conductances and allosteric modulation to both the endogenous neurosteroids and the AAS.…”

Section: Future Directionsmentioning

confidence: 99%

Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: Effects on reproductive function

Henderson

2007

Neuropharmacology

View full text Add to dashboard Cite

The hypothalamus, the seat of neuroendocrine control, is exquisitely sensitive to gonadal steroids. For decades it has been known that androgens, estrogens and progestins, acting through nuclear hormone receptors, elicit both organizational and activational effects in the hypothalamus and basal forebrain that are essential for reproductive function. While changes in gene expression mediated by these classical hormone pathways are paramount in governing both sexual differentiation and the neural control of reproduction, it is also clear that steroids impart critical control of neuroendocrine functions through nongenomic mechanisms. Specifically, endogenous neurosteroid derivatives of deoxycorticosterone, progesterone and testosterone, as well and synthetic anabolic androgenic steroids that are self-administered as drugs of abuse, elicit acute effects via allosteric modulation of γ-aminobutyric acid type A receptors. GABAergic transmission within the hypothalamus and basal forebrain is a key regulator of pubertal onset, the expression of sexual behaviors, pregnancy and parturition. Summarized here are the known actions of steroid modulators on GABAergic transmission within the hypothalamus/basal forebrain, with a focus on the medial preoptic area and the supraoptic/paraventricular nuclei that are known to be central players in the control of reproduction.

show abstract

“…The antibody against α4 subunit (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) has been characterized previously [1,12,32]. The antibodies against the γ2 (1-33) and δ (1-44) subunit of the GABA A receptor have been characterized extensively in the past by immunoprecipitation, Western blot, and immunohistochemistry [11,[19][20][21][22]32]. The antibodies against α1, α4, γ2 and δ were characterized by Western blot.…”

Section: Antibodiesmentioning

confidence: 99%

Distribution of α1, α4, γ2, and δ subunits of GABAA receptors in hippocampal granule cells

2004

View full text Add to dashboard Cite

GABA A receptors are pentamers composed of subunits derived from the α, β, γ, δ, θ, ε, and π gene families. α1, α4, γ2, and δ subunits are expressed in the dentate gyrus of the hippocampus, but their subcellular distribution has not been described. Hippocampal sections were double-labeled for the α1, α4, γ2, and δ subunits and GAD65 or gephyrin, and their subcellular distribution on dentate granule cells was studied by means of confocal laser scanning microscopy (CLSM). The synaptic versus extrasynaptic localization of these subunits was inferred by quantitative analysis of the frequency of colocalization of various subunits with synaptic markers in high-resolution images. GAD65 immunoreactive clusters colocalized with 26.24±0.86% of the α1 subunit immunoreactive clusters and 32.35±1.49% of the γ2 subunit clusters. In contrast, only 1.58±0.13% of the α4 subunit immunoreactive clusters and 1.92±0.15% of the δ subunit clusters colocalized with the presynaptic marker GAD65. These findings were confirmed by studying colocalization with immunoreactivity of a postsynaptic marker, gephyrin, which colocalized with 27.61±0.16% of the α1 subunit immunoreactive clusters and 23.45±0.32% of the γ2 subunit immunoreactive clusters. In contrast, only 1.90±0.13% of the α4 subunit immunoreactive clusters and 1.76±0.10% of the δ subunit clusters colocalized with gephyrin. These studies demonstrate that a subset of α1 and γ2 subunit clusters colocalize with synaptic markers in hippocampal dentate granule cells. Furthermore, all four subunits, α1, α4, γ2, and δ, are present in the extrasynaptic locations.

show abstract

GABAA receptors: immunocytochemical distribution of 13 subunits in the adult rat brain

Cited by 1,210 publications

References 96 publications

Activin tunes GABAergic neurotransmission and modulates anxiety-like behavior

Activin tunes GABAergic neurotransmission and modulates anxiety-like behavior

Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus: Effects on reproductive function

Distribution of α1, α4, γ2, and δ subunits of GABAA receptors in hippocampal granule cells

Contact Info

Product

Resources

About