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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: Data demonstrate that a single gene mutation can selectively alter the development of cortical interneurons in a region- and cell subtype-specific manner, with deficits leading to long-lasting changes in circuit organization and behavior.
Abstract: The generation of properly functioning circuits during brain development requires precise timing of cell migration and differentiation Disruptions in the developmental plan may lead to neurological and psychiatric disorders Neocortical circuits rely on inhibitory GABAergic interneurons, the majority of which migrate from subcortical sources We have shown that the pleiotropic molecule hepatocyte growth factor/scatter factor (HGF/SF) mediates interneuron migration Mice with a targeted mutation of the gene encoding urokinase plasminogen activator receptor (uPAR), a key component in HGF/SF activation and function, have decreased levels of HGF/SF and a 50% reduction in neocortical GABAergic interneurons at embryonic and perinatal ages Disruption of interneuron development leads to early lethality in most models Thus, the long-term consequences of such perturbations are unknown Mice of the uPAR −/− strain survive until adulthood, and behavior testing demonstrates that they have an increased anxiety state The uPAR −/− strain also exhibits spontaneous seizure activity and higher susceptibility to pharmacologically induced convulsions The neocortex of the adult uPAR −/− mouse exhibits a dramatic region- and subtype-specific decrease in GABA-immunoreactive interneurons Anterior cingulate and parietal cortical areas contain 50% fewer GABAergic interneurons compared with wild-type littermates However, interneuron numbers in piriform and visual cortical areas do not differ from those of normal mice Characterization of interneuron subpopulations reveals a near complete loss of the parvalbumin subtype, with other subclasses remaining intact These data demonstrate that a single gene mutation can selectively alter the development of cortical interneurons in a region- and cell subtype-specific manner, with deficits leading to long-lasting changes in circuit organization and behavior

337 citations

Journal ArticleDOI
18 Nov 2010-Neuron
TL;DR: In this article, the authors used array tomography to determine the composition of glutamate and GABA synapses in somatosensory cortex of Line-H-YFP Thy-1 transgenic mice.

333 citations

Journal ArticleDOI
TL;DR: Seizures are not generated in a normal circuit in which GABA-mediated inhibition is simply impaired, but in a profoundly rewired network in which several properties of GABA function are altered.

331 citations

Journal ArticleDOI
TL;DR: It is found that Tlx3 was required for specification of, and expressed in, glutamatergic neurons, and excess GABA-mediated inhibition caused dysfunction of central respiratory circuits in TlX3 mutant mice.
Abstract: Glutamatergic and GABAergic neurons mediate much of the excitatory and inhibitory neurotransmission, respectively, in the vertebrate nervous system. The process by which developing neurons select between these two cell fates is poorly understood. Here we show that the homeobox genes Tlx3 and Tlx1 determine excitatory over inhibitory cell fates in the mouse dorsal spinal cord. First, we found that Tlx3 was required for specification of, and expressed in, glutamatergic neurons. Both generic and region-specific glutamatergic markers, including VGLUT2 and the AMPA receptor Gria2, were absent in Tlx mutant dorsal horn. Second, spinal GABAergic markers were derepressed in Tlx mutants, including Pax2 that is necessary for GABAergic differentiation, Gad1/2 and Viaat that regulate GABA synthesis and transport, and the kainate receptors Grik2/3. Third, ectopic expression of Tlx3 was sufficient to suppress GABAergic differentiation and induce formation of glutamatergic neurons. Finally, excess GABA-mediated inhibition caused dysfunction of central respiratory circuits in Tlx3 mutant mice.

331 citations

Journal ArticleDOI
03 Oct 1997-Science
TL;DR: Activation of single ferret perigeniculate neurons generated three distinct patterns of GABAergic IPSPs in thalamocortical neurons of the dorsal lateral geniculate nucleus, which can reconfigure the operations of thalamOCortical networks into patterns of activity associated with waking, slow-wave sleep, and generalized seizures.
Abstract: The inhibitory gamma-aminobutyric acid-containing (GABAergic) neurons of the thalamic reticular and perigeniculate nuclei are involved in the generation of normal and abnormal synchronized activity in thalamocortical networks. An important factor controlling the generation of activity in this system is the amplitude and duration of inhibitory postsynaptic potentials (IPSPs) in thalamocortical cells, which depend on the pattern of activity generated in thalamic reticular and perigeniculate cells. Activation of single ferret perigeniculate neurons generated three distinct patterns of GABAergic IPSPs in thalamocortical neurons of the dorsal lateral geniculate nucleus: Low-frequency tonic discharge resulted in small-amplitude IPSPs mediated by GABAA receptors, burst firing resulted in large-amplitude GABAA IPSPs, and prolonged burst firing activated IPSPs mediated by GABAA and GABAB receptors. These functional properties of GABAergic inhibition can reconfigure the operations of thalamocortical networks into patterns of activity associated with waking, slow-wave sleep, and generalized seizures.

331 citations


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