title: Sleep spindles are generated in the absence of T-type calcium channel-mediated low-threshold burst firing of thalamocortical neurons.
abstract: T-type Ca(2+) 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 Ca(2+) 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.
authors.affiliation: Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-811, Korea.
authors.forename: Jungryun
authors.initials: J
authors.lastname: Lee
authors.forename: Kiyeong
authors.initials: K
authors.lastname: Song
authors.forename: Kyoobin
authors.initials: K
authors.lastname: Lee
authors.forename: Joohyeon
authors.initials: J
authors.lastname: Hong
authors.forename: Hyojung
authors.initials: H
authors.lastname: Lee
authors.forename: Sangmi
authors.initials: S
authors.lastname: Chae
authors.forename: Eunji
authors.initials: E
authors.lastname: Cheong
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
mesh_terms: D000818:Animals; D058256:Brain Waves / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000235:genetics; D004569:Electroencephalography; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism*; D010507:Periodicity; D012890:Sleep / Q000502:physiology*; D013788:Thalamus / Q000378:metabolism*
chemical_list: C498197:Cacna1g protein, mouse; D020747:Calcium Channels, T-Type