The schizophrenia risk gene product miR-137 alters presynaptic plasticity

DSpace/Manakin Repository

The schizophrenia risk gene product miR-137 alters presynaptic plasticity

Citable link to this page


Title: The schizophrenia risk gene product miR-137 alters presynaptic plasticity
Author: Siegert, Sandra; Seo, Jinsoo; Kwon, Ester J.; Rudenko, Andrii; Cho, Sukhee; Wang, Wenyuan; Flood, Zachary; Martorell, Anthony J.; Ericsson, Maria; Mungenast, Alison E.; Tsai, Li-Huei

Note: Order does not necessarily reflect citation order of authors.

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.
Full Text & Related Files:
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.
Published Version: doi:10.1038/nn.4023
Other Sources:
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at
Citable link to this page:
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)


Search DASH

Advanced Search