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Previous Article | Next Article
The Journal of Neuroscience, July 1, 2000, 20(13):5153-5162
Corticothalamic Inputs Control the Pattern of Activity Generated in Thalamocortical Networks
Hal Blumenfeld1, 2 and David A. McCormick1 1 Section of Neurobiology and 2 Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520
Absence seizures (3-4 Hz) and sleep spindles (6-14 Hz) occur mostly during slow-wave sleep and have been hypothesized to involve the same corticothalamic network. However, the mechanism by which this network transforms from one form of activity to the other is not well understood. Here we examine this question using ferret lateral geniculate nucleus slices and stimulation of the corticothalamic tract. A feedback circuit, meant to mimic the cortical influence in vivo, was arranged such that thalamic burst firing resulted in stimulation of the corticothalamic tract. Stimuli were either single shocks to mimic normal action potential firing by cortical neurons or high-frequency bursts (six shocks at 200 Hz) to simulate increased cortical firing, such as during seizures. With one corticothalamic stimulus per thalamic burst, 6-10 Hz oscillations resembling spindle waves were generated. However, if the stimulation was a burst, the network immediately transformed into a 3-4 Hz paroxysmal oscillation. This transition was associated with a strong increase in the burst firing of GABAergic perigeniculate neurons. In addition, thalamocortical neurons showed a transition from fast (100-150 msec) IPSPs to slow (~300 msec) IPSPs. The GABAB receptor antagonist CGP 35348 blocked the slow IPSPs and converted the 3-4 Hz paroxysmal oscillations back to 6-10 Hz spindle waves. Conversely, the GABAA receptor antagonist picrotoxin blocked spindle frequency oscillations resulting in 3-4 Hz oscillations with either single or burst stimuli. We suggest that differential activation of thalamic GABAA and GABAB receptors in response to varying corticothalamic input patterns may be critical in setting the oscillation frequency of thalamocortical network interactions.
Key words: GABA; corticothalamic; thalamocortical; absence seizures; petit mal; sleep spindles; epilepsy; sleep; networks
Copyright © 2000 Society for Neuroscience 0270-6474/00/20135153-10$05.00/0
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