Detection of a High-Turnover Serotonin Circuit in the Mouse Brain Using Mass Spectrometry Imaging
Eiji Sugiyama,
Matteo M. Guerrini,
Kurara Honda,
Yuko Hattori,
Manabu Abe,
Patrik Källback,
Per E. Andrén,
Kenji F. Tanaka,
Mitsutoshi Setou,
Sidonia Fagarasan,
Makoto Suematsu,
Yuki Sugiura
Affiliations
Eiji Sugiyama
Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan
Matteo M. Guerrini
Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Tsurumi Ward, Suehirocho, 1 Chome-7-22, Yokohama, Kanagawa Prefecture 230-0045, Japan
Kurara Honda
Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan
Yuko Hattori
Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan
Manabu Abe
Department of Animal Model Development, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8585, Japan
Patrik Källback
Medical Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Box 591 BMC, 75124 Uppsala, Sweden; Science for Life Laboratory, National Resource for Mass Spectrometry Imaging, Uppsala University, Box 591 BMC, 75124 Uppsala, Sweden
Per E. Andrén
Medical Mass Spectrometry Imaging, Department of Pharmaceutical Biosciences, Uppsala University, Box 591 BMC, 75124 Uppsala, Sweden; Science for Life Laboratory, National Resource for Mass Spectrometry Imaging, Uppsala University, Box 591 BMC, 75124 Uppsala, Sweden
Kenji F. Tanaka
Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan
Mitsutoshi Setou
Department of Cellular and Molecular Anatomy and International Mass Imaging Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan
Sidonia Fagarasan
Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Tsurumi Ward, Suehirocho, 1 Chome-7-22, Yokohama, Kanagawa Prefecture 230-0045, Japan
Makoto Suematsu
Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan
Yuki Sugiura
Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan; Corresponding author
Summary: Monoamine neurotransmitters are released by specialized neurons regulating behavioral, motor, and cognitive functions. Although the localization of monoaminergic neurons in the brain is well known, the distribution and kinetics of monoamines remain unclear. Here, we generated a murine brain atlas of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels using mass spectrometry imaging (MSI). We found several nuclei rich in both 5-HT and a catecholamine (DA or NE) and identified the paraventricular nucleus of the thalamus (PVT), where 5-HT and NE are co-localized. The analysis of 5-HT fluctuations in response to acute tryptophan depletion and infusion of isotope-labeled tryptophan in vivo revealed a close kinetic association between the raphe nuclei, PVT, and amygdala but not the other nuclei. Our findings imply the existence of a highly dynamic 5-HT-mediated raphe to PVT pathway that likely plays a role in the brain monoamine system. : Spectroscopy; Neuroscience; Systems Neuroscience Subject Areas: Spectroscopy, Neuroscience, Systems Neuroscience
