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Loss of MeCP2 leads to a host of synaptic phenotypes that are believed to underlie Rett syndrome pathophysiology. Synaptic deficits vary by brain region upon MeCP2 loss, suggesting distinct molecular alterations leading to disparate synaptic outcomes. In this study, we examined the contribution of MeCP2's newly described role in miRNA regulation to regional molecular and synaptic impairments. Two miRNAs, miR\u2010101a and miR\u2010203, were identified and confirmed as upregulated in MeCP2 KO mice in the hippocampus and cortex, respectively. miR\u2010101a overexpression in hippocampal cultures led to opposing effects at excitatory and inhibitory synapses and in spontaneous and evoked neurotransmission, revealing the potential for a single miRNA to broadly regulate synapse function in the hippocampus. These results highlight the importance of regional alterations in miRNA expression and the specific impact on synaptic function with potential implications for Rett syndrome.<\/jats:p>","DOI":"10.1002\/hipo.23455","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T07:24:59Z","timestamp":1658215499000},"page":"610-623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp>MeCP2<\/scp> loss\u2010of\u2010function dysregulates <scp>microRNAs<\/scp> regionally and disrupts excitatory\/inhibitory synaptic transmission balance"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9969-8637","authenticated-orcid":false,"given":"Patricia M.","family":"Horvath","sequence":"first","affiliation":[{"name":"Department of Pharmacology Vanderbilt University  Nashville Tennessee USA"},{"name":"Department of Neuroscience The University of Texas Southwestern Medical 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