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Optically activatable TrkB (optoTrkB) can temporarily and spatially evoke iPlasticity, and recently, optoTrkB (E281A) was developed as a variant that is highly sensitive to light stimulation while having lower basal activity compared to the original optoTrkB. In this study, we validate optoTrkB (E281A) activated in alpha calcium\/calmodulin-dependent protein kinase type II positive (CKII+) pyramidal neurons or parvalbumin-positive (PV+) interneurons in the mouse visual cortex by immunohistochemistry. OptoTrkB (E281A) was activated in PV+ interneurons and CKII+ pyramidal neurons with blue light (488 nm) through the intact skull and fur, and through a transparent skull, respectively. LED light stimulation significantly increased the intensity of phosphorylated ERK and CREB even through intact skull and fur. These findings indicate that the highly sensitive optoTrkB (E281A) can be used in iPlasticity studies of both inhibitory and excitatory neurons, with flexible stimulation protocols in behavioural studies.<\/jats:p>","DOI":"10.3390\/ijms231810249","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T20:52:51Z","timestamp":1662497571000},"page":"10249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Optical Activation of TrkB (E281A) in Excitatory and Inhibitory Neurons of the Mouse Visual Cortex"],"prefix":"10.3390","volume":"23","author":[{"given":"Antonia","family":"Lilja","sequence":"first","affiliation":[{"name":"Faculty of Psychology and Neuroscience, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00100 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuliano","family":"Didio","sequence":"additional","affiliation":[{"name":"Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00100 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jongryul","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won Do","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Biological Science, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea"},{"name":"Center for Cognition and Sociality, Institute for Basic Science (IBS), Daejeon 305-701, Korea"},{"name":"KAIST Institute for the BioCentury, KAIST, Daejeon 305-701, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1402-2791","authenticated-orcid":false,"given":"Eero","family":"Castr\u00e9n","sequence":"additional","affiliation":[{"name":"Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00100 Helsinki, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2595-7362","authenticated-orcid":false,"given":"Juzoh","family":"Umemori","sequence":"additional","affiliation":[{"name":"Neuroscience Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00100 Helsinki, Finland"},{"name":"Gene and Cell Technology, A.I. 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