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- W2980981605 endingPage "18.2019" @default.
- W2980981605 startingPage "ENEURO.0229" @default.
- W2980981605 abstract "Network excitability is governed by synaptic efficacy, intrinsic excitability, and the circuitry in which these factors are expressed. The complex interplay between these factors determines how circuits function and, at the extreme, their susceptibility to seizure. We have developed a sensitive, quantitative estimate of network excitability in freely behaving mice using a novel optogenetic intensity-response procedure. Synchronous activation of deep sublayer CA1 pyramidal cells produces abnormal network-wide epileptiform population discharges (PDs) that are nearly indistinguishable from spontaneously-occurring interictal spikes (IISs). By systematically varying light intensity, and therefore the magnitude of the optogenetically-mediated current, we generated intensity-response curves using the probability of PD as the dependent variable. Manipulations known to increase excitability, such as sub-convulsive doses (20 mg/kg) of the chemoconvulsant pentylenetetrazol (PTZ), produced a leftward shift in the curve compared to baseline. The anti-epileptic drug levetiracetam (LEV; 40 mk/kg), in combination with PTZ, produced a rightward shift. Optogenetically-induced PD threshold (oPDT) baselines were stable over time, suggesting the metric is appropriate for within-subject experimental designs with multiple pharmacological manipulations." @default.
- W2980981605 created "2019-10-25" @default.
- W2980981605 creator A5003083153 @default.
- W2980981605 creator A5063329043 @default.
- W2980981605 creator A5070496419 @default.
- W2980981605 creator A5076299671 @default.
- W2980981605 date "2019-10-16" @default.
- W2980981605 modified "2023-10-12" @default.
- W2980981605 title "Optogenetically-Induced Population Discharge Threshold as a Sensitive Measure of Network Excitability" @default.
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