title: Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition.
abstract: GABA is the major inhibitory transmitter in the brain and is released not only from a subset of neurons but also from glia. Although neuronal GABA is well known to be synthesized by glutamic acid decarboxylase (GAD), the source of glial GABA is unknown. After estimating the concentration of GABA in Bergmann glia to be around 5-10 mM by immunogold electron microscopy, we demonstrate that GABA production in glia requires MAOB, a key enzyme in the putrescine degradation pathway. In cultured cerebellar glia, both Ca(2+)-induced and tonic GABA release are significantly reduced by both gene silencing of MAOB and the MAOB inhibitor selegiline. In the cerebellum and striatum of adult mice, general gene silencing, knock out of MAOB or selegiline treatment resulted in elimination of tonic GABA currents recorded from granule neurons and medium spiny neurons. Glial-specific rescue of MAOB resulted in complete rescue of tonic GABA currents. Our results identify MAOB as a key synthesizing enzyme of glial GABA, which is released via bestrophin 1 (Best1) channel to mediate tonic inhibition in the brain.
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Center for Neural Science, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, Korea Department of Nanobiomedical Science, Dankook University, Chungnam, 330-714, Korea.
authors.forename: Bo-Eun
authors.initials: BE
authors.lastname: Yoon
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Center for Neural Science, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, Korea.
authors.forename: Junsung
authors.initials: J
authors.lastname: Woo
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Center for Neural Science, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, Korea.
authors.forename: Ye-Eun
authors.initials: YE
authors.lastname: Chun
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Center for Neural Science, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea.
authors.forename: Heejung
authors.initials: H
authors.lastname: Chun
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Korea.
authors.forename: Seonmi
authors.initials: S
authors.lastname: Jo
authors.affiliation: Department of Oral Anatomy and Neurobiology, BK21, School of Dentistry, Kyungpook National University, Daegu, 700-412, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Bae
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Center for Neural Science, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea KU-KIST School of Converging Science and Technology, Korea University, Seoul, 136-701, Korea.
authors.forename: Heeyoung
authors.initials: H
authors.lastname: An
authors.affiliation: Department of Nanobiomedical Science, Dankook University, Chungnam, 330-714, Korea.
authors.forename: Joo Ok
authors.initials: JO
authors.lastname: Min
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Center for Neural Science, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Center for Neural Science, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, Korea.
authors.forename: Kyung-Seok
authors.initials: KS
authors.lastname: Han
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea.
authors.forename: Hye Yun
authors.initials: HY
authors.lastname: Kim
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea.
authors.forename: Taekeun
authors.initials: T
authors.lastname: Kim
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea.
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Oral Anatomy and Neurobiology, BK21, School of Dentistry, Kyungpook National University, Daegu, 700-412, Republic of Korea.
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Bae
authors.affiliation: WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Center for Neural Science, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, Korea cjl@kist.re.kr.
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D009433:Neural Inhibition; D009457:Neuroglia / Q000378:metabolism* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D008995:Monoamine Oxidase; D002118:Calcium