Astrocytes Control Sensory Acuity via Tonic Inhibition in the Thalamus

Hankyul Kwak; Wuhyun Koh; Sangwoo Kim; Kiyeong Song; Jeong-Im Shin; Jung Moo Lee; Elliot H Lee; Jin Young Bae; Go Eun Ha; Ju-Eun Oh; Yongmin Mason Park; Sunpil Kim; Jiesi Feng; Seung Eun Lee; Ji Won Choi; Ki Hun Kim; Yoo Sung Kim; Junsung Woo; Dongsu Lee; Taehwang Son; Soon Woo Kwon; Ki Duk Park; Bo-Eun Yoon; Jaeick Lee; Yulong Li; Hyunbeom Lee; Yong Chul Bae; C Justin Lee; Eunji Cheong

doi:10.1016/j.neuron.2020.08.013

Astrocytes Control Sensory Acuity via Tonic Inhibition in the Thalamus

Neuron. 2020 Nov 25;108(4):691-706.e10. doi: 10.1016/j.neuron.2020.08.013. Epub 2020 Sep 8.

Authors

Hankyul Kwak¹, Wuhyun Koh², Sangwoo Kim¹, Kiyeong Song¹, Jeong-Im Shin³, Jung Moo Lee⁴, Elliot H Lee¹, Jin Young Bae⁵, Go Eun Ha¹, Ju-Eun Oh⁶, Yongmin Mason Park², Sunpil Kim⁷, Jiesi Feng⁸, Seung Eun Lee⁹, Ji Won Choi¹⁰, Ki Hun Kim¹¹, Yoo Sung Kim¹², Junsung Woo¹³, Dongsu Lee¹, Taehwang Son¹⁴, Soon Woo Kwon¹⁵, Ki Duk Park¹⁶, Bo-Eun Yoon¹², Jaeick Lee¹¹, Yulong Li¹⁷, Hyunbeom Lee⁶, Yong Chul Bae⁵, C Justin Lee¹⁸, Eunji Cheong¹⁹

Affiliations

¹ Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
² Division of Bio-Medical Science &Technology, KIST School, Korea University of Science and Technology, Seoul 02792, South Korea; Center for Glia-Neuron Interaction, Korea Institute of Science and Technology, Seoul 02792, South Korea; Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea.
³ Division of Bio-Medical Science &Technology, KIST School, Korea University of Science and Technology, Seoul 02792, South Korea; Center for Glia-Neuron Interaction, Korea Institute of Science and Technology, Seoul 02792, South Korea.
⁴ Center for Glia-Neuron Interaction, Korea Institute of Science and Technology, Seoul 02792, South Korea; Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, South Korea.
⁵ Department of Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 41566, South Korea.
⁶ Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul 02792, South Korea.
⁷ Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, South Korea.
⁸ State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China.
⁹ Virus Facility, Research Animal Resource Center, Korea Institute of Science and Technology, Seoul 02792, South Korea.
¹⁰ Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, South Korea.
¹¹ Doping Control Center, Korea Institute of Science and Technology, Seoul 02792, South Korea.
¹² Department of Molecular Biology, College of Natural Science, Dankook University, Cheonan 31116, South Korea.
¹³ Center for Glia-Neuron Interaction, Korea Institute of Science and Technology, Seoul 02792, South Korea.
¹⁴ School of Electrical and Electronic Engineering, Yonsei University, Seoul 03722, South Korea.
¹⁵ Radiation Medicine Clinical Research Division, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea.
¹⁶ Division of Bio-Medical Science &Technology, KIST School, Korea University of Science and Technology, Seoul 02792, South Korea; Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology, Seoul 02792, South Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, South Korea.
¹⁷ State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China.
¹⁸ Division of Bio-Medical Science &Technology, KIST School, Korea University of Science and Technology, Seoul 02792, South Korea; Center for Glia-Neuron Interaction, Korea Institute of Science and Technology, Seoul 02792, South Korea; Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea. Electronic address: cjl@ibs.re.kr.
¹⁹ Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea; POSTECH Biotech Center, POSTECH, Pohang, South Korea. Electronic address: eunjicheong@yonsei.ac.kr.

PMID: 32905785
DOI: 10.1016/j.neuron.2020.08.013

Abstract

Sensory discrimination is essential for survival. However, how sensory information is finely controlled in the brain is not well defined. Here, we show that astrocytes control tactile acuity via tonic inhibition in the thalamus. Mechanistically, diamine oxidase (DAO) and the subsequent aldehyde dehydrogenase 1a1 (Aldh1a1) convert putrescine into GABA, which is released via Best1. The GABA from astrocytes inhibits synaptically evoked firing at the lemniscal synapses to fine-tune the dynamic range of the stimulation-response relationship, the precision of spike timing, and tactile discrimination. Our findings reveal a novel role of astrocytes in the control of sensory acuity through tonic GABA release.

Keywords: Best1; aldehyde dehydrogenase; astrocyte; diamine oxidase; sensory acuity; tactile discrimination; temporal fidelity; thalamus; tonic GABA; tonic inhibition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aldehyde Dehydrogenase 1 Family / metabolism
Amine Oxidase (Copper-Containing) / metabolism
Animals
Astrocytes / metabolism
Astrocytes / physiology*
Astrocytes / ultrastructure
Bestrophins / biosynthesis
Bestrophins / genetics
Female
GABA Antagonists
Immunohistochemistry
Inhibitory Postsynaptic Potentials / physiology
Macrolides / pharmacology
Male
Mice
Mice, Knockout
Microscopy, Electron
Neural Inhibition / physiology*
Neurons / metabolism
Neurons / physiology
Patch-Clamp Techniques
Picrotoxin / pharmacology
Primary Cell Culture
Pyridazines / pharmacology
RNA, Small Interfering / pharmacology
Retinal Dehydrogenase / metabolism
Thalamus / physiology*
Touch Perception / physiology*
gamma-Aminobutyric Acid / biosynthesis
gamma-Aminobutyric Acid / pharmacology
gamma-Aminobutyric Acid / physiology*

Substances

Best1 protein, mouse
Bestrophins
GABA Antagonists
Macrolides
Pyridazines
RNA, Small Interfering
Picrotoxin
gamma-Aminobutyric Acid
concanamycin A
gabazine
Aldehyde Dehydrogenase 1 Family
ALDH1A1 protein, mouse
Retinal Dehydrogenase
Amine Oxidase (Copper-Containing)