| First Author | Siegert S | Year | 2015 |
| Journal | Nat Neurosci | Volume | 18 |
| Issue | 7 | Pages | 1008-16 |
| PubMed ID | 26005852 | Mgi Jnum | J:224478 |
| Mgi Id | MGI:5662336 | Doi | 10.1038/nn.4023 |
| Citation | Siegert S, et al. (2015) The schizophrenia risk gene product miR-137 alters presynaptic plasticity. Nat Neurosci 18(7):1008-16 |
| abstractText | Noncoding variants in the human MIR137 gene locus increase schizophrenia risk with genome-wide significance. However, the functional consequence of these risk alleles is unknown. Here we examined induced human neurons harboring the minor alleles of four disease-associated single nucleotide polymorphisms in MIR137. We observed increased MIR137 levels compared to those in major allele-carrying cells. microRNA-137 gain of function caused downregulation of the presynaptic target genes complexin-1 (Cplx1), Nsf and synaptotagmin-1 (Syt1), leading to impaired vesicle release. In vivo, miR-137 gain of function resulted in changes in synaptic vesicle pool distribution, impaired induction of mossy fiber long-term potentiation and deficits in hippocampus-dependent learning and memory. By sequestering endogenous miR-137, we were able to ameliorate the synaptic phenotypes. Moreover, reinstatement of Syt1 expression partially restored synaptic plasticity, demonstrating the importance of Syt1 as a miR-137 target. Our data provide new insight into the mechanism by which miR-137 dysregulation can impair synaptic plasticity in the hippocampus. |
