Two novel GABAA receptor subunits exist in distinct neuronal subpopulations

Shivers, Brenda D.; Killisch, Iris; Sprengel, Rolf; Sontheimer, Harald; Köhler, Martin; Schofield, Peter R.; Seeburg, Peter H.

doi:10.1016/0896-6273(89)90257-2

Cited by 517 publications

(228 citation statements)

References 24 publications

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“…GABA A receptors containing the delta subunit are restricted to these extrasynaptic locations (Nusser et al, 1998;Wei et al, 2003). Receptors containing the δ subunit are unique as they are benzodiazepine-insensitive (Shivers et al, 1989) and neurosteroid sensitive (Mihalek et al, 1999;Stell et al, 2003;Wohlfarth et al, 2002). GABA A receptors containing this subunit are highly abundant in the cerebellar granule cells, hippocampus and thalamus (Laurie et al, 1997;Laurie et al, 1992a) and cortex (Mihalek et al, 1999;Pirker et al, 2000).…”

Section: Gaba a Receptor Expression During Embryonic Developmentmentioning

confidence: 99%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

189

117

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Neurosteroids are a relatively new class of neuroactive compounds, brought to prominence in the past two decades. Despite knowing of their presence in the nervous system of various species for over twenty years and knowing of their functions as GABA A and NMDA ligands, new and unexpected functions of these compounds are continuously being identified. Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity. This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of four distinct neurosteroids -pregnenolone, progesterone, allopregnanolone and dehydroepiandrosterone.

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Section: Gaba a Receptor Expression During Embryonic Developmentmentioning

confidence: 99%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

189

117

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“…Presence of Extrasynaptic GABA A Rs in LC Neurons-Extrasynaptic GABA A Rs were first described in cerebellar cortical gray matter (37) and found later in many other brain areas, such as the cerebral cortex, dentate gyrus granule, thalamus, and neocortex (38 -43). Extrasynaptic GABA A Rs are sensitive to low levels of ambient GABA with little desensitization.…”

Section: Discussionmentioning

confidence: 99%

Methyl CpG Binding Protein 2 Gene Disruption Augments Tonic Currents of γ-Aminobutyric Acid Receptors in Locus Coeruleus Neurons

Zhong

Cui

Jin

et al. 2015

Journal of Biological Chemistry

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“…Sections were then incubated overnight at 37 Њ C with 75 l/section of hybridization buffer containing 50% deionized formamide, 10 mm dithiothreitol, 10 mm Tris (Ph 7.5), 600 mm sodium chloride, 1 mm EDTA, 10% dextran sulfate, 1 ϫ Denhardt's solution, 100 g salmon sperm DNA, 100 g/ml yeast tRNA, with 1 ϫ 10 6 CPM [ 35 S] ddATP labeled ␥ 2 oligonucleotide probe. The ␥ 2 oligonucleotide probe (5 Ј -3 Ј : GTC ATA GCC ATA TTC TTC ATC CCT CTC TTG AAG GTG GGT GGC; Shivers et al 1989) was synthesized (Beckman 1000 DNA Synthesizer, Beckman, USA) and labeled using a DNA 3 Ј -end labeling kit (Boehringer Mannheim, USA). Preliminary studies using a scrambled version of the probe yielded no specific signal on brain sections (data not shown).…”

Section: In Situ Hybridizationmentioning

confidence: 99%

The Effects of Early Rearing Environment on the Development of GABAA and Central Benzodiazepine Receptor Levels and Novelty-Induced Fearfulness in the Rat

Caldji

Francis

Sharma

et al. 2000

Neuropsychopharmacology

516

337

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We compared the effects of handling or maternal separation from the day following birth until postnatal day 14 on behavioral responses to novelty and on GABA A and central benzodiazepine (CBZ) receptor levels in the rat. As adults, handled animals showed reduced startle responsivity, increased exploration in a novel open field, and decreased novelty-induced suppression of feeding relative to the handled (H) and/or maternal separation (MS) groups. As compared with handled animals, both nonhandled (NH) and MS animals displayed: (1) reduced GABA A receptor levels in the locus coeruleus (LC) and the n. tractus solitarius (NTS); (2) reduced CBZ receptor sites in the central and lateral n. of the amygdala, the frontal cortex, and in the LC and NTS; and (3) The development of behavioral and endocrine responses to acute stress is greatly influenced by the early postnatal rearing environment (for reviews see Levine 1975;Denenberg 1964;Meaney et al. 1996). These environmental effects persist throughout the life of the animal, resulting in stable individual differences in stress reactivity. Indeed, there is considerable plasticity in the development of these systems. Postnatal handling during the first week of life greatly decreases behavioral fearfulness and hypothalamic-pituitary-adrenal (HPA) responses to stress; whereas, repeated periods of prolonged maternal separation produce enhanced reactivity. Increased stress reactivity has been associated with an enhanced risk for several forms of illness, including affective disorders, diabetes, autoimmune disorders, and coronary heart disease (Chrousos and Gold 1992;Higley et al. 1991;McEwen and Steller 1993;Seckl and Meaney 1994). Thus, in determining the magnitude of behavioral and endocrine responses to stress, early life events NO . 3 contribute to vulnerability to disease in later life (Seckl and Meaney 1994). The critical question, then, concerns the mechanisms for these early environmental effects on the development of behavioral and endocrine responses to stress.Postnatal handling has been shown to decrease fearfulness to novelty (Levine 1962(Levine , 1957Denenberg 1964;Bodnoff et al. 1987). As adults, handled (H) rats show reduced novelty-induced suppression of appetitive behavior and increased exploration in novel environments. The behavioral effects of repeated maternal separation in rats are less documented, although, in primates, there is considerable evidence for enhanced fearfulness in animals exposed to maternal separation in early life (Sackett 1969).The mechanisms underlying these early environmental effects on behavioral responses to novelty are unclear. Bodnoff et al. (1987) reported that neonatal handling increased forebrain central benzodiazepine (CBZ) receptor levels, with no indication of where in the forebrain such differences might exist. Nevertheless, these data are certainly consistent with the wellestablished, anxiolytic effects of benzodiazepines on behavioral responses to novelty (see File 1995 for a review). Moreover, these findings are a...

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Two novel GABAA receptor subunits exist in distinct neuronal subpopulations

Cited by 517 publications

References 24 publications

Neurosteroid regulation of central nervous system development

Neurosteroid regulation of central nervous system development

Methyl CpG Binding Protein 2 Gene Disruption Augments Tonic Currents of γ-Aminobutyric Acid Receptors in Locus Coeruleus Neurons

The Effects of Early Rearing Environment on the Development of GABAA and Central Benzodiazepine Receptor Levels and Novelty-Induced Fearfulness in the Rat

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