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This Article Full Text Full Text (PDF) All Versions of this Article: 102/1/203    most recent 91158.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Kleiman-Weiner, M. Articles by Huguenard, J. R. PubMed PubMed Citation Articles by Kleiman-Weiner, M. Articles by Huguenard, J. R.

Synergistic Roles of GABA_A Receptors and SK Channels in Regulating Thalamocortical Oscillations

Departments of ¹Biological Sciences and ²Neurology and Neurological Sciences, Stanford University, Stanford, California

Submitted 17 October 2008; accepted in final form 15 April 2009

Rhythmic oscillations throughout the cortex are observed during physiological and pathological states of the brain. The thalamus generates sleep spindle oscillations and spike-wave discharges characteristic of absence epilepsy. Much has been learned regarding the mechanisms underlying these oscillations from in vitro brain slice preparations. One widely used model to understand the epileptiform oscillations underlying absence epilepsy involves application of bicuculline methiodide (BMI) to brain slices containing the thalamus. BMI is a well-known GABA_A receptor blocker that has previously been discovered to also block small-conductance, calcium-activated potassium (SK) channels. Here we report that the robust epileptiform oscillations observed during BMI application rely synergistically on both GABA_A receptor and SK channel antagonism. Neither application of picrotoxin, a selective GABA_A receptor antagonist, nor application of apamin, a selective SK channel antagonist, alone yielded the highly synchronized, long-lasting oscillations comparable to those observed during BMI application. However, partial blockade of SK channels by subnanomolar concentrations of apamin combined with picrotoxin sufficiently replicated BMI oscillations. We found that, at the cellular level, apamin enhanced the intrinsic excitability of reticular nucleus (RT) neurons but had no effect on relay neurons. This work suggests that regulation of RT excitability by SK channels can influence the excitability of thalamocortical networks and may illuminate possible pharmacological treatments for absence epilepsy. Finally, our results suggest that changes in the intrinsic properties of individual neurons and changes at the circuit level can robustly modulate these oscillations.

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				A. S. Bryant, B. Li, M. P. Beenhakker, and J. R. Huguenard Maintenance of Thalamic Epileptiform Activity Depends on the Astrocytic Glutamate-Glutamine Cycle J Neurophysiol, November 1, 2009; 102(5): 2880 - 2888. [Abstract] [Full Text] [PDF]