Sleep spindles are generated in the absence of T-type calcium channel-mediated low-threshold burst firing of thalamocortical neurons

Jungryun Lee, Kiyeong Song, Kyoobin Lee, Joohyeon Hong, Hyojung Lee, Sangmi Chae, Eunji Cheong, Hee Sup Shin

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Abstract

T-type Ca2+ channels in thalamocortical (TC) neurons have long been considered to play a critical role in the genesis of sleep spindles, one of several TC oscillations. A classical model for TC oscillations states that reciprocal interaction between synaptically connected GABAergic thalamic reticular nucleus (TRN) neurons and glutamatergic TC neurons generates oscillations through T-type channel-mediated low-threshold burst firings of neurons in the two nuclei. These oscillations are then transmitted from TC neurons to cortical neurons, contributing to the network of TC oscillations. Unexpectedly, however, we found that both WT and KO mice for CaV3.1, the gene for T-type Ca2+ channels in TC neurons, exhibit typical waxing-and-waning sleep spindle waves at a similar occurrence and with similar amplitudes and episode durations during non-rapid eye movement sleep. Single-unit recording in parallel with electroencephalography in vivo confirmed a complete lack of burst firing in the mutant TC neurons. Of particular interest, the tonic spike frequency in TC neurons was significantly increased during spindle periods compared with nonspindle periods in both genotypes. In contrast, no significant change in burst firing frequency between spindle and nonspindle periods was noted in the WT mice. Furthermore, spindle-like oscillations were readily generated within intrathalamic circuits composed solely of TRN and TC neurons in vitro in both the KO mutant and WT mice. Our findings call into question the essential role of low-threshold burst firings in TC neurons and suggest that tonic firing is important for the generation and propagation of spindle oscillations in the TC circuit.

Original languageEnglish
Pages (from-to)20266-20271
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number50
DOIs
Publication statusPublished - 2013 Dec 10

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T-Type Calcium Channels
Sleep
Neurons
Thalamic Nuclei
Eye Movements
Electroencephalography

All Science Journal Classification (ASJC) codes

  • General

Cite this

Lee, Jungryun ; Song, Kiyeong ; Lee, Kyoobin ; Hong, Joohyeon ; Lee, Hyojung ; Chae, Sangmi ; Cheong, Eunji ; Shin, Hee Sup. / Sleep spindles are generated in the absence of T-type calcium channel-mediated low-threshold burst firing of thalamocortical neurons. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 50. pp. 20266-20271.
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Sleep spindles are generated in the absence of T-type calcium channel-mediated low-threshold burst firing of thalamocortical neurons. / Lee, Jungryun; Song, Kiyeong; Lee, Kyoobin; Hong, Joohyeon; Lee, Hyojung; Chae, Sangmi; Cheong, Eunji; Shin, Hee Sup.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 50, 10.12.2013, p. 20266-20271.

Research output: Contribution to journalArticle

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AU - Lee, Jungryun

AU - Song, Kiyeong

AU - Lee, Kyoobin

AU - Hong, Joohyeon

AU - Lee, Hyojung

AU - Chae, Sangmi

AU - Cheong, Eunji

AU - Shin, Hee Sup

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AB - T-type Ca2+ channels in thalamocortical (TC) neurons have long been considered to play a critical role in the genesis of sleep spindles, one of several TC oscillations. A classical model for TC oscillations states that reciprocal interaction between synaptically connected GABAergic thalamic reticular nucleus (TRN) neurons and glutamatergic TC neurons generates oscillations through T-type channel-mediated low-threshold burst firings of neurons in the two nuclei. These oscillations are then transmitted from TC neurons to cortical neurons, contributing to the network of TC oscillations. Unexpectedly, however, we found that both WT and KO mice for CaV3.1, the gene for T-type Ca2+ channels in TC neurons, exhibit typical waxing-and-waning sleep spindle waves at a similar occurrence and with similar amplitudes and episode durations during non-rapid eye movement sleep. Single-unit recording in parallel with electroencephalography in vivo confirmed a complete lack of burst firing in the mutant TC neurons. Of particular interest, the tonic spike frequency in TC neurons was significantly increased during spindle periods compared with nonspindle periods in both genotypes. In contrast, no significant change in burst firing frequency between spindle and nonspindle periods was noted in the WT mice. Furthermore, spindle-like oscillations were readily generated within intrathalamic circuits composed solely of TRN and TC neurons in vitro in both the KO mutant and WT mice. Our findings call into question the essential role of low-threshold burst firings in TC neurons and suggest that tonic firing is important for the generation and propagation of spindle oscillations in the TC circuit.

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