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| Item Type: | Article |
|---|---|
| Title: | miR-7 controls glutamatergic transmission and neuronal connectivity in a Cdr1as-dependent manner |
| Creators Name: | Cerda Jara, C.A., Kim, S.J., Thomas, G., Farsi, Z., Zolotarov, G., Dube, G., Deter, A., Bahry, E., Georgii, E., Woehler, A., Piwecka, M. and Rajewsky, N. |
| Abstract: | The circular RNA (circRNA) Cdr1as is conserved across mammals and highly expressed in neurons, where it directly interacts with microRNA miR-7. However, the biological function of this interaction is unknown. Here, using primary cortical murine neurons, we demonstrate that stimulating neurons by sustained depolarization rapidly induces two-fold transcriptional upregulation of Cdr1as and strong post-transcriptional stabilization of miR-7. Cdr1as loss causes doubling of glutamate release from stimulated synapses and increased frequency and duration of local neuronal bursts. Moreover, the periodicity of neuronal networks increases, and synchronicity is impaired. Strikingly, these effects are reverted by sustained expression of miR-7, which also clears Cdr1as molecules from neuronal projections. Consistently, without Cdr1as, transcriptomic changes caused by miR-7 overexpression are stronger (including miR-7-targets downregulation) and enriched in secretion/synaptic plasticity pathways. Altogether, our results suggest that in cortical neurons Cdr1as buffers miR-7 activity to control glutamatergic excitatory transmission and neuronal connectivity important for long-lasting synaptic adaptations. |
| Keywords: | circRNA, miRNA, Neuronal Activity, Cdr1as, miR-7, Animals, Mice |
| Source: | EMBO Reports |
| ISSN: | 1469-221X |
| Publisher: | Oxford University Press |
| Volume: | 25 |
| Number: | 7 |
| Page Range: | 3039 |
| Date: | July 2024 |
| Official Publication: | https://doi.org/10.1038/s44319-024-00168-9 |
| PubMed: | View item in PubMed |
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