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Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by δ subunit-containing GABAA receptors
- B. Stell, S. Brickley, C. Y. Tang, M. Farrant, I. Módy
- Biology, PsychologyProceedings of the National Academy of Sciences…
- 17 November 2003
It is reported that, at concentrations known to occur in vivo, neuroactive steroids specifically enhance a tonic inhibitory conductance in central neurons that is mediated by extrasynaptic δ subunit-containing GABAARs.
Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke.
- A. Clarkson, Ben S. Huang, Sarah E. Macisaac, I. Módy, S. Carmichael
- Biology, PsychologyNature
- 11 November 2010
This work shows that after a stroke in mice, tonic neuronal inhibition is increased in the peri-infarct zone, and identifies new pharmacological targets that provide the rationale for a novel strategy to promote recovery after stroke and possibly other brain injuries.
Which GABAA Receptor Subunits Are Necessary for Tonic Inhibition in the Hippocampus?
Depending on the cell type, the α5 and δ subunits are the principal GABAAR subunits responsible for mediating the lion's share of tonic inhibition in hippocampal neurons.
Ovarian cycle–linked changes in GABAA receptors mediating tonic inhibition alter seizure susceptibility and anxiety
Disturbances of neuronal excitability changes during the ovarian cycle may elevate seizure frequency in women with catamenial epilepsy and enhance anxiety in premenstrual dysphoric disorder (PMDD).…
Selective modulation of tonic and phasic inhibitions in dentate gyrus granule cells.
It is demonstrated that a tonic GABA(A) receptor-mediated conductance can be recorded from dentate gyrus granule cells of adult rats in in vitro slice preparations, and distinct pharmacological tools to selectively modify tonic and phasic inhibitions are identified, allowing future studies to investigate their specific roles in neuronal function.
Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices.
In both hippocampal regions, the epileptiform activity evolved without significant alterations in the resting membrane potential (RMP) and input resistance (RN) of the neurons, although a 2- to 5-mV reduction in action potential threshold was noted.
Increased number of synaptic GABAA receptors underlies potentiation at hippocampal inhibitory synapses
The postsynaptic insertion of new GABAA receptors and the corresponding increase in post Synaptic responses augmenting the efficacy of mammalian inhibitory synapses are established.
Extrasynaptic GABAA Receptors: Their Function in the CNS and Implications for Disease
Activation of GABAA Receptors: Views from Outside the Synaptic Cleft
Receptors with Different Affinities Mediate Phasic and Tonic GABAA Conductances in Hippocampal Neurons
It is demonstrated that a low concentration of the highly specific competitive GABA(A) antagonist SR95531 (gabazine) reduces phasic inhibition in hippocampal granule cells by 71% but has no effect on tonic inhibition, whereas a high concentration (10 microm) of the antagonist blocked both conductances.