In Vivo Visualization of Subtle, Transient, and Local Activity of Astrocytes Using an Ultrasensitive Ca2+ Indicator
Kazunori Kanemaru,
Hiroshi Sekiya,
Ming Xu,
Kaname Satoh,
Nami Kitajima,
Keitaro Yoshida,
Yohei Okubo,
Takuya Sasaki,
Satoru Moritoh,
Hidetoshi Hasuwa,
Masaru Mimura,
Kazuki Horikawa,
Ko Matsui,
Takeharu Nagai,
Masamitsu Iino,
Kenji F. Tanaka
Affiliations
Kazunori Kanemaru
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan
Hiroshi Sekiya
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan
Ming Xu
Department of Neuropsychiatry, School of Medicine, Keio University, Shinjuku, Tokyo 160-8582, Japan
Kaname Satoh
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan
Nami Kitajima
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan
Keitaro Yoshida
Department of Neuropsychiatry, School of Medicine, Keio University, Shinjuku, Tokyo 160-8582, Japan
Yohei Okubo
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan
Takuya Sasaki
Neurobiology Section and Center for Neural Circuits and Behavior, Division of Biological Sciences, University of California, San Diego, San Diego, CA, 92093-0357, USA
Satoru Moritoh
Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
Hidetoshi Hasuwa
Genome Information Research Center, Osaka University, Suita 565-0871, Japan
Masaru Mimura
Department of Neuropsychiatry, School of Medicine, Keio University, Shinjuku, Tokyo 160-8582, Japan
Kazuki Horikawa
Support Center for Advanced Medical Sciences, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan
Ko Matsui
Division of Interdisciplinary Medical Science, Center for Neuroscience, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Takeharu Nagai
The Institute of Scientific and Industrial Research, Osaka University, Ibaraki 567-0047, Japan
Masamitsu Iino
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo, Tokyo 113-0033, Japan
Kenji F. Tanaka
Department of Neuropsychiatry, School of Medicine, Keio University, Shinjuku, Tokyo 160-8582, Japan
Astrocytes generate local calcium (Ca2+) signals that are thought to regulate their functions. Visualization of these signals in the intact brain requires an imaging method with high spatiotemporal resolution. Here, we describe such a method using transgenic mice expressing the ultrasensitive ratiometric Ca2+ indicator yellow Cameleon-Nano 50 (YC-Nano50) in astrocytes. In these mice, we detected a unique pattern of Ca2+ signals. These occur spontaneously, predominantly in astrocytic fine processes, but not the cell body. Upon sensory stimulation, astrocytes initially responded with Ca2+ signals at fine processes, which then propagated to the cell body. These observations suggest that astrocytic fine processes function as a high-sensitivity detector of neuronal activities. Thus, the method provides a useful tool for studying the activity of astrocytes in brain physiology and pathology.
