Hyun-U Cho,#1 Sunpil Kim,#2,3 Jeongeun Sim,1 Seulkee Yang,4 Heeyoung An,2,3 Min-Ho Nam,corresponding author4,5 Dong-Pyo Jang,corresponding author1 and C. Justin Leecorresponding author2,3
1Department of Biomedical Engineering, Hanyang University, Seoul, Korea
2KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Korea
3Center for Cognition and Sociality, Institute for Basic Science, Daejeon, Korea
4Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Korea
5Department of KHU-KIST Convergence Science and Technology, Kyung Hee University, Seoul, Korea
Min-Ho Nam, Email: [email protected]
corresponding authorCorresponding author.
Monoamine oxidase (MAO) is believed to mediate the degradation of monoamine neurotransmitters, including dopamine, in the brain. Between the two types of MAO, MAO-B has been believed to be involved in dopamine degradation, which supports the idea that the therapeutic efficacy of MAO-B inhibitors in Parkinson’s disease can be attributed to an increase in extracellular dopamine concentration. However, this belief has been controversial. Here, by utilizing in vivo phasic and basal electrochemical monitoring of extracellular dopamine with fast-scan cyclic voltammetry and multiple-cyclic square wave voltammetry and ex vivo fluorescence imaging of dopamine with GRABDA2m, we demonstrate that MAO-A, but not MAO-B, mainly contributes to striatal dopamine degradation. In contrast, our whole-cell patch-clamp results demonstrated that MAO-B, but not MAO-A, was responsible for astrocytic GABA-mediated tonic inhibitory currents in the rat striatum. We conclude that, in contrast to the traditional belief, MAO-A and MAO-B have profoundly different roles: MAO-A regulates dopamine levels, whereas MAO-B controls tonic GABA levels.
To visualize the GRABDA2m sensor, a blue LED (pE340fura, CoolLED) was applied to brain slices under a fluorescent upright microscope with a ×10 objective.
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The 340 nm and 380 nm LED illumination system provides the optimum excitation wavelengths for Fura-2-based calcium imaging, allowing high-precision, stable, high-throughput imaging with video-rate time resolution.
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