T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites

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T-type Ca2+ channels (T channels) underlie rhythmic burst discharges during neuronal oscillations that are typical during sleep. However, the Ca2+-dependent effectors that are selectively regulated by T currents remain unknown. We found that, in dendrites of nucleus reticularis thalami (nRt), intracellular Ca2+ concentration increases were dominated by Ca2+ influx through T channels and shaped rhythmic bursting via competition between Ca2+-dependent small-conductance (SK)-type K+ channels and Ca2+ uptake pumps. Oscillatory bursting was initiated via selective activation of dendritically located SK2 channels, whereas Ca2+ sequestration by sarco/endoplasmic reticulum Ca2+-ATPases (SERCAs) and cumulative T channel inactivation dampened oscillations. Sk2−/− (also known as Kcnn2) mice lacked cellular oscillations, showed a greater than threefold reduction in low-frequency rhythms in the electroencephalogram of non–rapid-eye-movement sleep and had disrupted sleep. Thus, the interplay of T channels, SK2 channels and SERCAs in nRt dendrites comprises a specialized Ca2+ signaling triad to regulate oscillatory dynamics related to sleep.

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Figure 1: SK currents are selectively activated by T currents to control nRt cell oscillations.
Figure 2: T channels dominate dendritic [Ca2+]i increases during low-threshold bursts.
Figure 3: SK currents in nRt are carried by SK2-containing SK channels.
Figure 4: SK2 channel subunits are selectively expressed in nRt dendrites.
Figure 5: Repetitive low-threshold bursting is accompanied by a decrease in the amplitude of Δ[Ca2+]i.
Figure 6: SERCAs antagonize SK2 current activation by T-type Ca2+, but not by HVA Ca2+, currents.
Figure 7: SERCAs modulate the strength of nRt oscillations.
Figure 8: Lack of Sk2 greatly impacts the EEG and fragmentation of NREMS.


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We thank M. Tafti, K. Vogt and N. Wanaverbecq for constructive input and A. Reisch for carrying out preliminary electrophysiological experiments. We thank L. Acsády, A. Destexhe, B. Gähwiler, U. Gerber, C. Kopp and D. Ulrich for stimulating discussions and helpful comments on the manuscript. This work was supported by grants from the Swiss National Science Foundation (A.L.), the US National Institutes of Health (P.F. and J.P.A.) and the Spanish Ministry of Education and Science (R.L.).

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Correspondence to Anita Lüthi.

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Supplementary Text and Figures

Supplementary Figures 1–5, Supplementary Table 1, Supplementary Note and Supplementary Methods (PDF 2441 kb)

Supplementary Movie 1

Fluorescent signals in a dendrite of a nRt neuron filled with the Ca2+ dye magfura-2 during a dampened electrical oscillation. (WMV 482 kb)

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Cueni, L., Canepari, M., Luján, R. et al. T-type Ca2+ channels, SK2 channels and SERCAs gate sleep-related oscillations in thalamic dendrites. Nat Neurosci 11, 683–692 (2008) doi:10.1038/nn.2124

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