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J Physiol. 2014 Nov 15;592(22):4951-68. doi: 10.1113/jphysiol.2014.278754. Epub 2014 Sep 19.

Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition.

Author information

1
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.
2
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.
3
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.
4
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.
5
Department of Oral Anatomy and Neurobiology, BK21, School of Dentistry, Kyungpook National University, Daegu, 700-412, Republic of Korea.
6
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.
7
Department of Nanobiomedical Science, Dankook University, Chungnam, 330-714, Korea.
8
WCI Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Korea.
9
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.

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.

PMID:
25239459
PMCID:
PMC4259537
DOI:
10.1113/jphysiol.2014.278754
[Indexed for MEDLINE]
Free PMC Article

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