dc.contributor.author | Siegert, Sandra | en_US |
dc.contributor.author | Seo, Jinsoo | en_US |
dc.contributor.author | Kwon, Ester J. | en_US |
dc.contributor.author | Rudenko, Andrii | en_US |
dc.contributor.author | Cho, Sukhee | en_US |
dc.contributor.author | Wang, Wenyuan | en_US |
dc.contributor.author | Flood, Zachary | en_US |
dc.contributor.author | Martorell, Anthony J. | en_US |
dc.contributor.author | Ericsson, Maria | en_US |
dc.contributor.author | Mungenast, Alison E. | en_US |
dc.contributor.author | Tsai, Li-Huei | en_US |
dc.date.accessioned | 2016-02-01T15:45:27Z | |
dc.date.issued | 2015 | en_US |
dc.identifier.citation | Siegert, S., J. Seo, E. J. Kwon, A. Rudenko, S. Cho, W. Wang, Z. Flood, et al. 2015. “The schizophrenia risk gene product miR-137 alters presynaptic plasticity.” Nature neuroscience 18 (7): 1008-1016. doi:10.1038/nn.4023. http://dx.doi.org/10.1038/nn.4023. | en |
dc.identifier.issn | 1097-6256 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:24983896 | |
dc.description.abstract | Non-coding variants in the human MIR137 gene locus increase schizophrenia risk at a genome-wide significance level. 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 (SNPs) in MIR137, and observed increased MIR137 levels compared to major allele-carrying cells. We found that miR-137 gain-of-function causes 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 results in changes in synaptic vesicle pool distribution, impaired mossy fiber-LTP induction 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. | en |
dc.language.iso | en_US | en |
dc.relation.isversionof | doi:10.1038/nn.4023 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506960/pdf/ | en |
dash.license | LAA | en_US |
dc.title | The schizophrenia risk gene product miR-137 alters presynaptic plasticity | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Nature neuroscience | en |
dash.depositing.author | Ericsson, Maria | en_US |
dc.date.available | 2016-02-01T15:45:27Z | |
dc.identifier.doi | 10.1038/nn.4023 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Ericsson, Maria | |