{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:34:14Z","timestamp":1787027654912,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"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":["32171005"],"award-info":[{"award-number":["32171005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and technology development plan project of Jilin Province, China","award":["JJKH20261242KJ"],"award-info":[{"award-number":["JJKH20261242KJ"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Locus coeruleus (LC) noradrenergic neurons project their axons to the cerebellar cortex and modulate cerebellar circuit function via distinct adrenergic receptor (AR) subtypes. The present study investigated the mechanism by which optogenetic activation of LC noradrenergic neurons modulates facial stimulation-evoked long-term synaptic plasticity at cerebellar mossy fiber-granule cell (MF-GrC) synapses in urethane-anesthetized DBH-Cre mice. Blockade of GABAA receptors, 20 Hz facial stimulation induced MF-GrC long-term potentiation (LTP) in the control group, and this LTP was impaired by optogenetic activation of LC noradrenergic neurons via \u03b12-ARs. Meanwhile, facial stimulation induced LTP of glutamate sensor fluorescence in the granular layer, which was abolished by chemogenetic activation of LC noradrenergic neurons. Following NMDA receptor blockade, optogenetic activation of LC noradrenergic neurons triggered facial stimulation-induced MF-GrC long-term depression (LTD) via \u03b12A-ARs. Optogenetically activated LC noradrenergic neuron-induced MF-GrC LTD was abolished by protein kinase A (PKA) inhibition but not by protein kinase C inhibition. Immunofluorescence results revealed abundant \u03b12A-AR expression in the granular layer, with particularly high levels in glomeruli, and no colocalization with the glutamate sensor. These results indicate that optogenetic activation of LC noradrenergic neurons impairs facial stimulation-induced MF-GrC LTP by triggering presynaptic LTD via the \u03b12A-AR\/PKA signaling cascade.<\/jats:p>","DOI":"10.3390\/biology15050406","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:06:59Z","timestamp":1772467619000},"page":"406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic Activation of Locus Coeruleus Noradrenergic Neurons Modulates Cerebellar MF-GrC Synaptic Plasticity via Presynaptic \u03b12-AR\/PKA Signaling in Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Ying-Han","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China"},{"name":"Department of Neural Circuit, Brain Science Institute, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-Dong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China"},{"name":"Department of Neural Circuit, Brain Science Institute, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7631-4440","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neural Circuit, Brain Science Institute, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Zhi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China"},{"name":"Department of Neural Circuit, Brain Science Institute, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji 133002, China"},{"name":"Department of Neural Circuit, Brain Science Institute, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Brain Science Institute, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Brain Science Institute, Jilin Medical University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mapelli, L., Solinas, S., and D\u2019Angelo, E. 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