Reciprocal inhibitory connections regulate the spatiotemporal properties of intrathalamic oscillations.
Mice with an inactivated GABA(A) receptor beta(3) subunit gene have features of Angelman syndrome, including absence-like seizures. This suggests the occurrence of abnormal hypersynchrony in the thalamocortical system. Within the thalamus, the efficacy of inhibitory synapses between thalamic reticular (RE) neurons is selectively compromised, and thalamic oscillations in vitro are prolonged and lack spatial phase gradients (). Here we used computational models to examine how intra-RE inhibition regulates intrathalamic oscillations. A major effect is an abbreviation of network responses, which is caused by long-lasting intra-RE inhibition that shunts recurrent excitatory input. In addition, differential activation of RE cells desynchronizes network activity. Near the slice center, where many cells are initially activated, there is a resultant high level of intra-RE inhibition. This leads to RE cell burst truncation in the central region and a gradient in the timing of thalamocortical cell activity similar to that observed in vitro. Although RE cell burst durations were shortened by this mechanism, there was very little effect on the times at which RE cells began to burst. The above results depended on widespread stimuli that activated RE cells in regions larger than the diameter of intra-RE connections. By contrast, more focal stimuli could elicit oscillations that lasted several cycles and remained confined to a small region. These results suggest that intra-RE inhibition restricts intrathalamic activity to particular spatiotemporal patterns to allow focal recurrent activity that may be relevant for normal thalamocortical function while preventing widespread synchronization as occurs in seizures.
Sohal
V S
VS
Department of Neurology, Stanford University School of Medicine, Stanford, California 94305-5122, USA.
Huntsman
M M
MM
Huguenard
J R
JR
D017204:Angelman Syndrome / Q000503:physiopathology; D000818:Animals; D004832:Epilepsy, Absence / Q000503:physiopathology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D010507:Periodicity; D011930:Reaction Time / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D013788:Thalamus / Q000166:cytology* / Q000502:physiology
D011963:Receptors, GABA-A