| First Author | Heyer MP | Year | 2026 |
| Journal | bioRxiv | Mgi Jnum | J:391176 |
| Mgi Id | MGI:8401163 | Doi | 10.64898/2026.06.29.734826 |
| Citation | Heyer MP, et al. (2026) Cerebellar microRNA-206 tunes Purkinje neuron firing dynamics to control sensorimotor gating. bioRxiv |
| abstractText | MicroRNAs are potent regulators of gene expression in the brain, yet the cellular mechanisms through which they shape neuronal activity and behavior remain poorly understood. MicroRNA-206 (miR-206) has been genetically and transcriptionally linked to schizophrenia and other neuropsychiatric disorders, but its functions in the nervous system are largely unknown. Here we show that miR-206 expression in the brain is restricted to postnatal cerebellar Purkinje cells (PCs). miR-206 was dispensable for PC cell fate specification, dendritic morphogenesis, and cerebellar-regulated motor coordination. Transcriptional profiling with single-nucleus and spatial resolution, integrated with Ago2-associated miRNA-target repression mapping (HITS-CLIP) and ribosome-associated RNA profiling (TRAP-seq), showed that miR-206 regulates translational programs in PCs controlling neuronal excitability. Accordingly, miR-206 deficiency increased the tonic firing of PCs, whereas elevating miR-206 expression shifted PCs from tonic to high-frequency burst firing. Constitutive or PC-specific deletion of miR-206 impaired prepulse inhibition (PPI) of the acoustic startle response, a conserved form of sensorimotor gating disrupted in schizophrenia and related disorders. Restoration of miR-206 expression in PCs rescued PPI deficits in miR-206-deficient mice, while elevating miR-206 expression in PCs impaired PPI in wild-type animals. Together, these findings reveal that a schizophrenia-linked microRNA tunes Purkinje neuron firing dynamics to control sensorimotor gating. |
