title: Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness.
abstract: In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of CaV3.1 T-type Ca(2+) channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking CaV3.1 channels (CaV3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that CaV3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (CaV3.1 WT). Intriguingly, we also found that CaV3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, CaV3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in CaV3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of CaV3.1 WT mice, during unconsciousness. These results suggest that the CaV3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states.
authors.affiliation: Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016; Marine Biological Laboratory, Woods Hole, MA 02543;
authors.forename: Soonwook
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016; Marine Biological Laboratory, Woods Hole, MA 02543;
authors.forename: Eunah
authors.initials: E
authors.lastname: Yu
authors.affiliation: Department of Mathematics, Pohang University of Science and Technology, Pohang 790-784, Republic of Korea.
authors.forename: Seongwon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016; Marine Biological Laboratory, Woods Hole, MA 02543; rodolfo.llinas@nyumc.org.
authors.forename: Rodolfo R
authors.initials: RR
authors.lastname: Llinás
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology*; D002940:Circadian Rhythm; D051379:Mice; D013788:Thalamus / Q000502:physiology*; D014474:Unconsciousness
chemical_list: C498197:Cacna1g protein, mouse; D020747:Calcium Channels, T-Type
keywords: coherence; electroencephalogram; local field potential; mediodorsal thalamus