Altered thalamocortical rhythmicity and connectivity in mice lacking Ca(V)3.1 T-type Ca2+ channels in unconsciousness

作者：Choi Soonwook; Yu Eunah; Lee Seongwon; Llinas Rodolfo R^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(25): 7839-7844.

DOI：10.1073/pnas.1420983112

• electroencephalogram
• local field potential
• mediodorsal thalamus
• coherence

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 Ca(V)3.1 T-type Ca2+ channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking Ca(V)3.1 channels (Ca(V)3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that Ca(V)3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (Ca(V)3.1 WT). Intriguingly, we also found that Ca(V)3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, Ca(V)3.1 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 Ca(V)3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of Ca(V)3.1 WT mice, during unconsciousness. These results suggest that the Ca(V)3.1 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.

• 出版日期2015-6-23