Abstract

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.

1. Division of Pharmacology and Neurobiology, Biozentrum, University of Basel, Klingelbergstr. 70, CH-4056 Basel, Switzerland.
2. Departamento de Ciencias Médicas, Crib-Facultad De Medicina, Campus Biosanitario C/ Almansa 14, Universidad de Castilla-La Mancha, 02006 Albacete, Spain.
3. Center for Integrative Genomics, Génopode Building, Quartier UNIL-Sorge, University of Lausanne, CH-1015 Lausanne-Dorigny, Switzerland.
4. Department of Anatomy, Hokkaido University School of Medicine, Kita-15 Nishi-7 Kita-ku Sapporo 060-8638, Japan.
5. Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
6. Department of Cell Biology and Morphology, Faculty of Biology and Medicine, Rue du Bugnon 9, University of Lausanne, CH-1005 Lausanne, Switzerland.

Correspondence to: Anita Lüthi^1,6 e-mail: anita.luthi@unil.ch

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