Serotonergic neurons control cortical neuronal intracellular energy dynamics by modulating astrocyte-neuron lactate shuttle
Akiyo Natsubori,
Shinobu Hirai,
Soojin Kwon,
Daisuke Ono,
Fei Deng,
Jinxia Wan,
Momoka Miyazawa,
Takashi Kojima,
Haruo Okado,
Akihiro Karashima,
Yulong Li,
Kenji F. Tanaka,
Makoto Honda
Affiliations
Akiyo Natsubori
Sleep Disorders Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan; Corresponding author
Shinobu Hirai
Sleep Disorders Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan
Soojin Kwon
Sleep Disorders Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan
Daisuke Ono
Department of Neuroscience Ⅱ, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan; Department of Neural Regulation, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Fei Deng
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China
Jinxia Wan
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China
Momoka Miyazawa
Sleep Disorders Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan; Faculty of Science Division Ⅱ, Tokyo University of Science, Shinjuku-ku, Tokyo 162-8601, Japan
Takashi Kojima
Sleep Disorders Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan
Haruo Okado
Sleep Disorders Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan
Akihiro Karashima
Department of Electronics, Graduate School of Engineering, Tohoku Institute of Technology, Sendai 982-8577, Japan
Yulong Li
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China
Kenji F. Tanaka
Division of Brain Sciences, Institute for Advanced Medical Research, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
Makoto Honda
Sleep Disorders Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan
Summary: The central serotonergic system has multiple roles in animal physiology and behavior, including sleep-wake control. However, its function in controlling brain energy metabolism according to the state of animals remains undetermined. Through in vivo monitoring of energy metabolites and signaling, we demonstrated that optogenetic activation of raphe serotonergic neurons increased cortical neuronal intracellular concentration of ATP, an indispensable cellular energy molecule, which was suppressed by inhibiting neuronal uptake of lactate derived from astrocytes. Raphe serotonergic neuronal activation induced cortical astrocytic Ca2+ and cAMP surges and increased extracellular lactate concentrations, suggesting the facilitation of lactate release from astrocytes. Furthermore, chemogenetic inhibition of raphe serotonergic neurons partly attenuated the increase in cortical neuronal intracellular ATP levels as arousal increased in mice. Serotonergic neuronal activation promoted an increase in cortical neuronal intracellular ATP levels, partly mediated by the facilitation of the astrocyte-neuron lactate shuttle, contributing to state-dependent optimization of neuronal intracellular energy levels.
