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dc.contributor.authorChin, Pei Wernen_US
dc.contributor.authorWan, Jinxiaen_US
dc.contributor.authorLi, Yulongen_US
dc.contributor.authorAugustine, George Jamesen_US
dc.identifier.citationChin, P. W., Wan, J., Li, Y. & Augustine, G. J. (2022). Cerebellar modulation of anxiety: serotonergic involvement examined via a new 5-HT sensor. Neuroscience 2022.en_US
dc.description.abstractCerebellar involvement in anxiety and anxiety-related behavior is supported by numerous clinical and animal studies (Behav. Brain Res. 112:107). Because the neuromodulator serotonin (5-HT) is well-known to play a role in anxiety (Nature 537:97) and serotonergic axons are amongst the most abundant fibers in the cerebellar cortex (Neuroscience 462:106), we determined whether cerebellar 5-HT is involved in anxiety. We first identified a locus for anxiety within the mouse cerebellum. We found that photostimulation of lobule VII in transgenic mice expressing channelrhodopsin in molecular layer interneurons (Cell Rep. 7:1601) caused a 67% decrease in time spent in the open quadrants of an elevated-zero maze (EZM; n = 8), indicating an anxiogenic effect. This is consistent with a previous observation that inhibiting lobule VII interneurons decreases anxiety (eLife 7: e36401) and indicates that lobule VII output is important for anxiety. To measure 5-HT levels in lobule VII, we expressed a novel fluorescent 5-HT indicator (GRAB5HT2h) with improved sensitivity to 5-HT compared to previous sensors (Nat. Neurosci. 24:746). GRAB5HT2h fiber photometry revealed higher 5-HT levels when mice were in open quadrants of the EZM, compared to the closed quadrants, indicating that 5-HT is higher during a low-anxiety state. To determine whether 5-HT levels affect anxiety, we optogenetically controlled the activity of serotonergic axons in lobule VII of a transgenic mouse line expressing channelrhodopsin or archaerhodopsin in serotonergic neurons (PNAS 102:16472). Photostimulation of 5-HT fibers caused a 106% increase in the amount of time spent in open quadrants of the EZM (n = 8), indicating an anxiolytic effect. Conversely, photoinhibition of 5-HT fibers produced an 81% decrease in the time spent in the open quadrants (n = 4), indicating an anxiogenic effect. Collectively, these results support the hypothesis that 5-HT levels in cerebellar lobule VII regulate anxiety, with higher 5-HT reducing anxiety.en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.rights© 2022 Society for Neuroscience. All rights reserved.en_US
dc.subjectScience::Biological sciences::Zoology::Animal behavioren_US
dc.titleCerebellar modulation of anxiety: serotonergic involvement examined via a new 5-HT sensoren_US
dc.typeConference Paperen
dc.contributor.schoolInterdisciplinary Graduate School (IGS)en_US
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.conferenceNeuroscience 2022en_US
dc.contributor.organizationSchool of Life Sciences, Peking Universityen_US
dc.contributor.organizationPKU-IDG/McGovern Inst. for Brain Res, Peking Universityen_US
dc.contributor.organizationPeking-Tsinghua Ctr. for Life Sciences, Acad. for Advanced Interdisciplinary Studies, Peking Universityen_US
dc.contributor.organizationChinese Institute for Brain Research (CIBR)en_US
dc.citation.conferencelocationSan Diego, California, USAen_US
dc.description.acknowledgementGrant/Other Support: : Ministry of Education, Singapore, MOE AcRF Tier 3 Award MOE2017-T3-1-002, MOE AcRF Tier 2 Award MOE2016-T2-1-097 and Interdisciplinary Graduate School bench fees.en_US
item.fulltextNo Fulltext- Kong Chian School of Medicine-
Appears in Collections:IGS Conference Papers
LKCMedicine Conference Papers

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