{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:18:23Z","timestamp":1761092303721,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Projects of the Ministry of Science and Technology of China","award":["2021ZD0202300"],"award-info":[{"award-number":["2021ZD0202300"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundations of China","doi-asserted-by":"crossref","award":["32070986","32171005"],"award-info":[{"award-number":["32070986","32171005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>17\u03b2-estradiol (E2) enhances the cerebellar molecular layer interneurons (MLIs)\u2014Purkinje cells (PCs) synaptic transmission via activation of the Er\u03b2 in vivo in mice. Whether E2 regulates cerebellar MLI-PC synaptic plasticity is unknown. To investigate the mechanism of E2, we evaluated the modulation of facial stimulation-evoked MLI-PC long-term plasticity in mice. Cell-attached recordings from PCs of Crus II were performed using an Axopatch-700B patch-clamp amplifier. The MLI-PC synaptic transmission was evoked by facial stimulation. Immunohistochemistry was used to detect the expression of ER\u03b2. Under control conditions, 1 Hz facial stimuli induced long-term depression (LTD) at MLI-PC synapses, characterized by a sustained reduction in P1 amplitude and a simple spike (SS) pause. The facial stimulus-induced MLI-PC LTD was completely prevented by E2, but this effect was reversed by a selective ER\u03b1\/ER\u03b2 antagonist, ICI182780. Blockade of cannabinoid receptor 1 (CB1R) eliminated the MLI-PC LTD under control conditions, but revealed an E2-triggered long-term potentiation (LTP). The E2-triggered MLI-PC LTP persisted in the presence of an ER\u03b1 antagonist but was absent in the presence of an ER\u03b2 antagonist PHTPP. The E2-triggered MLI-PC LTP remained unaffected by protein kinase A inhibition but was abolished by inhibition of protein kinase C (PKC) and intracellular Ca2+ depletion. Moreover, ER\u03b2 immunoreactivity was abundantly distributed around dendrites and somas of PCs in the Crus II region of the mouse cerebellar cortex. The present results suggest that E2 activates ER\u03b2, thereby triggering facial stimulation-induced MLI-PC LTP via the PKC signaling cascade, which occludes CB1R-dependent MLI-PC LTD in the cerebellar cortex of mice in vivo.<\/jats:p>","DOI":"10.3390\/ijms26209973","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T15:20:12Z","timestamp":1760973612000},"page":"9973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Estradiol Triggers Cerebellar MLI-PC LTP via ER\u03b2\/Protein Kinase C Signaling Cascades in Mice In Vivo"],"prefix":"10.3390","volume":"26","author":[{"given":"Zhao-Yi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China"},{"name":"Department of Neural Circuit, Institute of Brain Science, Jilin Medical University, Jilin 132013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China"},{"name":"Department of Neural Circuit, Institute of Brain Science, Jilin Medical University, Jilin 132013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Ze","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neural Circuit, Institute of Brain Science, Jilin Medical University, Jilin 132013, China"},{"name":"Department of Physiology, College of Basic Medicine, Jilin Medical University, Jilin 132013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Yue","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neural Circuit, Institute of Brain Science, Jilin Medical University, Jilin 132013, China"},{"name":"Department of Physiology, College of Basic Medicine, Jilin Medical University, Jilin 132013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neural Circuit, Institute of Brain Science, Jilin Medical University, Jilin 132013, China"},{"name":"Department of Physiology, College of Basic Medicine, Jilin Medical University, Jilin 132013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7379-1374","authenticated-orcid":false,"given":"Yuki","family":"Todo","sequence":"additional","affiliation":[{"name":"Faculty of Electrical, Information and Communication Engineering, Kanazawa University, Kanazawa 920-1192, Ishikawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Computer Engineering and Science, Shanghai University, Shanghai 200444, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Cong","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Neural Circuit, Institute of Brain Science, Jilin Medical University, Jilin 132013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin-Yong","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Neural Circuit, Institute of Brain Science, Jilin Medical University, Jilin 132013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6921-5028","authenticated-orcid":false,"given":"Chun-Ping","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China"},{"name":"Department of Neural Circuit, Institute of Brain Science, Jilin Medical University, Jilin 132013, China"},{"name":"Department of Physiology, College of Basic Medicine, Jilin Medical University, Jilin 132013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2152-3024","authenticated-orcid":false,"given":"Yin-Hua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neural Circuit, Institute of Brain Science, Jilin Medical University, Jilin 132013, China"},{"name":"Department of Neurology, College of Medicine, Yanbian University, Yanji 133002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8825-4707","authenticated-orcid":false,"given":"De-Lai","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China"},{"name":"Department of Neural Circuit, Institute of Brain Science, Jilin Medical University, Jilin 132013, China"},{"name":"Department of Physiology, College of Basic Medicine, Jilin Medical University, Jilin 132013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1146\/annurev.ne.12.030189.000505","article-title":"Long-term depression","volume":"12","author":"Ito","year":"1989","journal-title":"Annu. 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