{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:12:27Z","timestamp":1787497947896,"version":"build-2736575974"},"reference-count":83,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      MicroRNAs are small, highly conserved non\u2010coding RNAs that negatively regulate mRNA translation and stability. In the brain, miRNAs contribute to neuronal development, synaptogenesis, and synaptic plasticity. MicroRNA 138\u20105p (miR\u2010138\u20105p) controls inhibitory synaptic transmission in the hippocampus and is highly expressed in cerebellar excitatory neurons. However, its specific role in cerebellar synaptic transmission remains unknown. Here, we investigated excitatory transmission in the cerebellum of mice expressing a sponge construct that sequesters endogenous miR\u2010138\u20105p. Mossy fibre stimulation\u2010evoked EPSCs in granule cells were \u223c40% larger in miR\u2010138\u20105p sponge mice compared to controls. Furthermore, we observed larger miniature EPSC amplitudes, suggesting an increased number of functional postsynaptic AMPA receptors. High\u2010frequency train stimulation revealed enhanced short\u2010term depression following miR\u2010138\u20105p downregulation. Together with computational modelling, this suggests a negative regulation of presynaptic release probability. Overall, our results demonstrate that miR\u2010138\u20105p suppresses synaptic strength through pre\u2010 and postsynaptic mechanisms, providing a potentially powerful mechanism for tuning excitatory synaptic input into the cerebellum.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16731-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>MicroRNAs are powerful regulators of mRNA translation and control key cell biological processes including synaptic transmission, but their role in regulating synaptic function in the cerebellum has remained elusive.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In this study, we investigated how microRNA\u2010138\u20105p (miR\u2010138\u20105p) modulates excitatory transmission at adult murine cerebellar mossy fibre to granule cell synapses.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Downregulation of miR\u2010138\u20105p enhances excitatory synaptic strength at the cerebellar input layer and increases short\u2010term depression.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>miR\u2010138\u20105p exerts its regulatory function through both pre\u2010 and postsynaptic mechanisms by negatively regulating release probability at mossy fibre boutons, as well as functional AMPA receptor numbers in granule cells.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These findings provide insights into the role of miR\u2010138\u20105p in the cerebellum and expand our understanding of microRNA\u2010dependent control of excitatory synaptic transmission and short\u2010term plasticity.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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