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The Journal of Neuroscience, October 1, 2003, 23(26):8978-8988

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Behavioral/Systems/Cognitive
Inhibitory Interconnections Control Burst Pattern and Emergent Network Synchrony in Reticular Thalamus

Vikaas S. Sohal and John R. Huguenard

Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, California 94305-5122

Inhibitory connections between neurons of the thalamic reticular (RE) nucleus are thought to help prevent spike-wave discharge (SWD), characteristic of generalized absence epilepsy, in thalamic and thalamocortical circuits. Indeed, oscillations in thalamic slices resemble SWD when intra-RE inhibition is blocked and are suppressed when intra-RE inhibition is enhanced. To elucidate the cellular mechanisms underlying these network changes, we recorded from RE cells during oscillations in thalamic slices and either blocked intra-RE inhibition with picrotoxin or enhanced it with clonazepam. We found that intra-RE inhibition limits the number and synchrony, but not the duration, of RE cell bursts. We then performed simulations that demonstrate how inhibition can shift network activity into a desynchronized mode simply by vetoing occasional RE cell bursts. In contrast, when intra-RE inhibition is blocked, RE cells burst synchronously, enabling even short RE cell bursts to promote epileptogenesis in two ways: first, by activating GABA_B receptors, and second, through the GABA_B receptor-independent emergence of network synchrony.

Key words: generalized absence epilepsy; spike wave discharge; thalamus; oscillations; computational modeling; GABA_A receptors

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Received June 13, 2003; revised August 1, 2003; accepted August 13, 2003.

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