{"intvolume":"        18","extern":1,"publisher":"Nature Publishing Group","publist_id":"5308","abstract":[{"text":"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.","lang":"eng"}],"publication_status":"published","citation":{"ama":"Siegert S, Seo J, Kwon E, et al. The schizophrenia risk gene product miR-137 alters presynaptic plasticity. <i>Nature Neuroscience</i>. 2015;18:1008-1016. doi:<a href=\"https://doi.org/10.1038/nn.4023\">10.1038/nn.4023</a>","ieee":"S. Siegert <i>et al.</i>, “The schizophrenia risk gene product miR-137 alters presynaptic plasticity,” <i>Nature Neuroscience</i>, vol. 18. Nature Publishing Group, pp. 1008–1016, 2015.","chicago":"Siegert, Sandra, Jinsoo Seo, Ester Kwon, Andrii Rudenko, Sukhee Cho, Wenyuan Wang, Zachary Flood, et al. “The Schizophrenia Risk Gene Product MiR-137 Alters Presynaptic Plasticity.” <i>Nature Neuroscience</i>. Nature Publishing Group, 2015. <a href=\"https://doi.org/10.1038/nn.4023\">https://doi.org/10.1038/nn.4023</a>.","short":"S. Siegert, J. Seo, E. Kwon, A. Rudenko, S. Cho, W. Wang, Z. Flood, A. Martorell, M. Ericsson, A. Mungenast, L. Tsai, Nature Neuroscience 18 (2015) 1008–1016.","apa":"Siegert, S., Seo, J., Kwon, E., Rudenko, A., Cho, S., Wang, W., … Tsai, L. (2015). The schizophrenia risk gene product miR-137 alters presynaptic plasticity. <i>Nature Neuroscience</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/nn.4023\">https://doi.org/10.1038/nn.4023</a>","mla":"Siegert, Sandra, et al. “The Schizophrenia Risk Gene Product MiR-137 Alters Presynaptic Plasticity.” <i>Nature Neuroscience</i>, vol. 18, Nature Publishing Group, 2015, pp. 1008–16, doi:<a href=\"https://doi.org/10.1038/nn.4023\">10.1038/nn.4023</a>.","ista":"Siegert S, Seo J, Kwon E, Rudenko A, Cho S, Wang W, Flood Z, Martorell A, Ericsson M, Mungenast A, Tsai L. 2015. The schizophrenia risk gene product miR-137 alters presynaptic plasticity. Nature Neuroscience. 18, 1008–1016."},"acknowledgement":"S.S. was supported by a Human Frontier Science Program (HFSP) long-term postdoctoral fellowship and a Swiss National Science Foundation fellowship for prospective researchers. E.J.K. was supported by a Simons Foundation Postdoctoral Fellowship. A.R. was supported by a NARSAD Young Investigator Award. This work was supported by a Seed Grant from the Simons Center for the Social Brain and US National Institutes of Health grant RO1 MH 091115 to L.-H.T.","doi":"10.1038/nn.4023","author":[{"orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Sandra Siegert","last_name":"Siegert"},{"last_name":"Seo","full_name":"Seo, Jinsoo","first_name":"Jinsoo"},{"last_name":"Kwon","full_name":"Kwon, Ester J","first_name":"Ester"},{"full_name":"Rudenko, Andrii","last_name":"Rudenko","first_name":"Andrii"},{"full_name":"Cho, Sukhee","last_name":"Cho","first_name":"Sukhee"},{"first_name":"Wenyuan","full_name":"Wang, Wenyuan","last_name":"Wang"},{"last_name":"Flood","full_name":"Flood, Zachary C","first_name":"Zachary"},{"full_name":"Martorell, Anthony J","last_name":"Martorell","first_name":"Anthony"},{"last_name":"Ericsson","full_name":"Ericsson, Maria","first_name":"Maria"},{"last_name":"Mungenast","full_name":"Mungenast, Alison E","first_name":"Alison"},{"first_name":"Lihuei","full_name":"Tsai, Lihuei","last_name":"Tsai"}],"date_published":"2015-07-01T00:00:00Z","type":"journal_article","day":"01","year":"2015","status":"public","month":"07","page":"1008 - 1016","date_updated":"2021-01-12T06:53:18Z","volume":18,"date_created":"2018-12-11T11:54:05Z","publication":"Nature Neuroscience","_id":"1802","title":"The schizophrenia risk gene product miR-137 alters presynaptic plasticity","quality_controlled":0}