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The neuropsychological manifestations affect multiple domains of cognition and behavior, but their etiology remains elusive. Transgenic DMSXL mice carry the DM1 mutation, show behavioral abnormalities, and express low levels of GLT1, a critical regulator of glutamate concentration in the synaptic cleft. However, the impact of glutamate homeostasis on neurotransmission in DM1 remains unknown. We confirmed reduced glutamate uptake in the DMSXL hippocampus. Patch clamp recordings in hippocampal slices revealed increased amplitude of tonic glutamate currents in DMSXL CA1 pyramidal neurons and DG granule cells, likely mediated by higher levels of ambient glutamate. Unexpectedly, extracellular GABA levels and tonic current were also elevated in DMSXL mice. Finally, we found evidence of synaptic dysfunction in DMSXL mice, suggestive of abnormal short-term plasticity, illustrated by an altered LTP time course in DG and in CA1. Synaptic dysfunction was accompanied by RNA foci accumulation in localized areas of the hippocampus and by the mis-splicing of candidate genes with relevant functions in neurotransmission. Molecular and functional changes triggered by toxic RNA may induce synaptic abnormalities in restricted brain areas that favor neuronal dysfunction.<\/jats:p>","DOI":"10.3390\/ijms23020592","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T01:15:26Z","timestamp":1641518126000},"page":"592","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["DM1 Transgenic Mice Exhibit Abnormal Neurotransmitter Homeostasis and Synaptic Plasticity in Association with RNA Foci and Mis-Splicing in the Hippocampus"],"prefix":"10.3390","volume":"23","author":[{"given":"Brigitte","family":"Potier","sequence":"first","affiliation":[{"name":"LuMIn, CNRS FRE2036, ENS Paris-Saclay, CentraleSupelec, Universit\u00e9 Paris-Saclay, 91190 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4436-6712","authenticated-orcid":false,"given":"Louison","family":"Lallemant","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Myologie, Institut de Myologie, Inserm, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9836-0391","authenticated-orcid":false,"given":"Sandrine","family":"Parrot","sequence":"additional","affiliation":[{"name":"Lyon Neuroscience Research Center, Inserm U1028, CNRS UMR5292, Universit\u00e9 Lyon 1, 69500 Bron, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Huguet-Lachon","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Myologie, Institut de Myologie, Inserm, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Gourdon","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Myologie, Institut de Myologie, Inserm, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Dutar","sequence":"additional","affiliation":[{"name":"LuMIn, CNRS FRE2036, ENS Paris-Saclay, CentraleSupelec, Universit\u00e9 Paris-Saclay, 91190 Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3533-0873","authenticated-orcid":false,"given":"M\u00e1rio","family":"Gomes-Pereira","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Myologie, Institut de Myologie, Inserm, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"ref_1","unstructured":"Harper, P.S.P.S. 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