
The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown
Published: May 11, 2025
Abstract MicroRNAs are small, highly conserved non‐coding RNAs that negatively regulate mRNA translation and stability. In the brain, miRNAs contribute to neuronal development, synaptogenesis, synaptic plasticity. MicroRNA 138‐5p (miR‐138‐5p) controls inhibitory transmission in hippocampus is expressed cerebellar excitatory neurons. However, its specific role remains unknown. Here, we investigated cerebellum of mice expressing a sponge construct sequesters endogenous miR‐138‐5p. Mossy fibre stimulation‐evoked EPSCs granule cells were ∼40% larger miR‐138‐5p compared controls. Furthermore, observed miniature EPSC amplitudes, suggesting an increased number functional postsynaptic AMPA receptors. High‐frequency train stimulation revealed enhanced short‐term depression following downregulation. Together with computational modelling, this suggests negative regulation presynaptic release probability. Overall, our results demonstrate suppresses strength through pre‐ mechanisms, providing potentially powerful mechanism for tuning input into cerebellum. image Key points regulators control key cell biological processes including transmission, but their regulating function has remained elusive. study, how microRNA‐138‐5p modulates at adult murine mossy synapses. Downregulation enhances layer increases depression. exerts regulatory both mechanisms by probability boutons, as well receptor numbers cells. These findings provide insights expand understanding microRNA‐dependent
Language: Английский