Asset Details
Do you wish to reserve the book?
GABAB autoreceptor-mediated cell type-specific reduction of inhibition in epileptic mice
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
GABAB autoreceptor-mediated cell type-specific reduction of inhibition in epileptic mice
Do you wish to request the book?
GABAB autoreceptor-mediated cell type-specific reduction of inhibition in epileptic mice
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
GABAB autoreceptor-mediated cell type-specific reduction of inhibition in epileptic mice
2013
Overview
GABA B receptors (GABA BRs) mediate slow inhibitory effects on neuronal excitability and synaptic transmission in the brain. However, the GABA BR agonist baclofen can also promote excitability and seizure generation in human patients and animals models. Here we show that baclofen has concentration-dependent effects on the hippocampal network in a mouse model of mesial temporal lobe epilepsy. Application of baclofen at a high dose (10 mg/kg i.p.) reduced the power of γ oscillations and the frequency of pathological discharges in the Cornu Ammonis area 3 (CA3) area of freely moving epileptic mice. Unexpectedly, at a lower dose (1 mg/kg), baclofen markedly increased γ activity accompanied by a higher incidence of pathological discharges. Intracellular recordings from CA3 pyramidal cells in vitro further revealed that, although at a high concentration (10 µM), baclofen invariably resulted in hyperpolarization, at low concentrations (0.5 µM), the drug had divergent effects, producing depolarization and an increase in firing frequency in epileptic but not control mice. These excitatory effects were mediated by the selective muting of inhibitory cholecystokinin-positive basket cells (CCK ⁺ BCs), through enhanced inhibition of GABA release via presynaptic GABA BRs. We conclude that cell type–specific up-regulation of GABA BR-mediated autoinhibition in CCK ⁺ BCs promotes aberrant high frequency oscillations and hyperexcitability in hippocampal networks of chronic epileptic mice.
Publisher
National Academy of Sciences,National Acad Sciences
