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GABAergic

About: GABAergic is a research topic. Over the lifetime, 9595 publications have been published within this topic receiving 473568 citations.


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Journal ArticleDOI
TL;DR: The present data outline the quantitative aspects of the cellular architecture of hippocampal GABAergic system and also give complementary information to the recent multidisciplinary analyses at the single cell level.

131 citations

Journal ArticleDOI
TL;DR: The expression by different populations of interneurons suggests that ErbB4 can modulate several microcircuits within the hippocampus and mediate the previously reported effects of NRG1 on network oscillations and synaptic plasticity.
Abstract: Neuregulins (NRGs) are ligands of ErbB receptor tyrosine kinases. The NRG1-ErbB4 pathway has been shown to modulate hippocampal synaptic plasticity and network oscillations in the adult rodent brain. To identify cells that mediate these effects, here we determine the expression pattern of ErbB4 in four functionally distinct classes of interneurons that represent the majority of all inhibitory neurons in the adult hippocampus. On the basis of data from nine mice and 25,000 cells, we show that ErbB4 is expressed in cells that are positive for cholecystokinin (CCK, 54%), parvalbumin (PV, 42%), or neuronal nitric oxide synthase (nNOS, 39%) in a layer-specific and region-specific manner, whereas cells expressing somatostatin (SOM) are rarely immunoreactive for ErbB4 (1%). We next compared the numerical density (cells/mm(3)) and the distribution of interneurons between ErbB4-/- mice and wildtype controls. Based on data from 25 mice and 56,000 cells, we detected reductions of PV-positive and nNOS-positive cells in knockouts (-24% and -27%, respectively) but only a minor reduction of CCK-positive cells; no changes in SOM-positive cells were observed. The overall reduction of interneurons was verified by quantification of GAD67-immunoreactive cells (-24% in ErbB4-/- mice). The reduction of interneurons along the dorsoventral axis was more severe in intermediate and ventral portions than in the dorsal hippocampus, and regional reductions occurred in the CA1-3 regions and subiculum, whereas we found no significant changes in the dentate gyrus (DG). The expression by different populations of interneurons suggests that ErbB4 can modulate several microcircuits within the hippocampus and mediate the previously reported effects of NRG1 on network oscillations and synaptic plasticity. The selective reduction of GABAergic cells in ErbB4-/- mice is consistent with the role of NRG-ErbB4 signaling in the generation and migration of interneurons during development, and with neuronal and behavioral functional deficits in adult ErbB4 knockouts.

131 citations

Journal Article
TL;DR: No simple relationship was observed between the degree of motor impairment caused by either ethanol or gamma-acetylenic GABA and changes in GABA concentration in three brain areas, and the interaction does not involve a direct activation of GABA receptors by ethanol.
Abstract: Direct or indirect pharmacological manipulation of gamma-aminobutyric acid (GABA) receptor activity was examined in relation to the motor incoordinating actions of ethanol in the rat. Ethanol (1.13-3.0 g/kg i.p.) caused a dose-dependent increase in the height of aerial righting. This motor impairment was increased selectively by intracisternal injection of the GABA agonists muscimol (0.10 microgram), 4,5,6,7-tetrahydroisoxazole(5,4-c) pyridin(3-ol) (1.0 microgram) and GABA (1000 micrograms). The GABA antagonist, bicuculline (1.0 and 5.0 micrograms intracisternally), reduced impairment. Thus, direct manipulation of GABA receptor activity modulated motor incoordination caused by ethanol. In addition, indirect-acting GABA-mimetics, such as gamma-acetylenic GABA (100 mg/kg i.p.), aminooxyacetic acid (50 mg/kg i.p.), ethanolamine-O-sulfate (250 mg/kg i.p.) and L-2,4-diaminobutyric acid (600 mg/kg i.p.) all potentiated the increase in the height of aerial righting caused by ethanol treatment. Failure of ethanol to modify the binding of [3H]muscimol to cerebral cortical membranes in vitro suggested there was no direct competition for GABA binding sites or facilitation of the binding of GABA to these sites by ethanol. Also, no simple relationship was observed between the degree of motor impairment caused by either ethanol or gamma-acetylenic GABA and changes in GABA concentration in three brain areas. Although GABAergic neurons may be involved in the mechanism underlying ethanol-induced depression of motor coordination, the interaction does not involve a direct activation of GABA receptors by ethanol.

131 citations

Journal Article
TL;DR: This study supports the hypothesis that GABAergic mechanisms play a role in the etiology or pathophysiology of Autistic Disorder, however, the hypothesis remains unspecified owing to lack of research.
Abstract: Background Autistic Disorder is an early-onset developmental disorder with severe lifelong impact on social functioning, communication, and behavior. There is currently no marker or cure. The pathophysiology and etiology are obscure. Evidence for abnormal gamma-aminobutyric acid (GABA) function in Autistic Disorders is limited. A few case-reports and small studies have reported differences in GABA levels in plasma, platelets, and urine, compared to controls. Further studies on abnormalities of GABA function in Autistic Disorder are warranted. Material/methods Plasma GABA levels were measured using a new and sensitive technique, based on gas chromatography/mass spectrometry, in a small group of youngsters with Autistic Disorder and Attention-Deficit/Hyperactivity Disorder. Participants were outpatients between ages 5-15, satisfying modern criteria for these disorders. Results Elevated plasma GABA levels were found in youngsters with Autistic Disorder. Psychotropic medications did not seem to affect plasma GABA levels in this study. Plasma GABA levels decreased with age. Conclusions Elevated plasma GABA levels may be a biochemical marker of Autistic Disorder. This study supports the hypothesis that GABAergic mechanisms play a role in the etiology or pathophysiology of Autistic Disorder. However, the hypothesis remains unspecified owing to lack of research. Future studies on the clinical associations of seizure disorders, mood disorders, and catatonia in autistic people may provide the necessary data to formulate a coherent theory of GABA dysfunction in Autistic Disorder. More trials of medication with known or suspected effects on GABA function are warranted.

131 citations

Journal ArticleDOI
Isobel Lever1, Joanna Cunningham1, John Grist1, Ping K. Yip1, Marzia Malcangio1 
TL;DR: It is concluded that BDNF‐induced release of GABA could be a mechanism to explain the antinociceptive action of intrathecal BDNF in neuropathic animals.
Abstract: Damage to peripheral nerves is associated with changes in excitability and/or phenotype of primary afferent neurons as well as increased neuronal excitability (central sensitization) and reduced inhibitory tone in the dorsal horn. For instance, in dorsal root ganglia (DRG) brain derived neurotrophic factor (BDNF) is down-regulated in small cells whilst de novo expressed in large diameter cells. In the dorsal horn, GABA content is decreased. In this study, in a dorsal horn, 'with dorsal roots attached' preparation obtained from spinal nerve lesioned Wistar rats, stimulation of ipsilateral dorsal roots at either A fibre or A + C fibre strength did not evoke release of BDNF. In separate experiments, activity-induced release of GABA in the isolated dorsal horn of neuropathic rats was significantly reduced compared to release in sham operated rats. GABA release could be significantly restored following topical application of BDNF through the dorsal horn preparation. Finally, neuropathic rats developed thermal and mechanical hypersensitivity and thermal hyperalgesia was reduced by intrathecal injection of BDNF. We concluded that BDNF-induced release of GABA could be a mechanism to explain the antinociceptive action of intrathecal BDNF in neuropathic animals. Furthermore, reduced availability of sensory neuron-derived BDNF might contribute to the reduced GABAergic tone in the dorsal horn of neuropathic rats.

130 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023371
2022749
2021341
2020320
2019301
2018297