{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:20:50Z","timestamp":1790763650117,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T00:00:00Z","timestamp":1682467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Caen Normandy"},{"name":"Normandy Region"},{"name":"INSERM"},{"name":"FHU A2M2P"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The subtype 6 of the serotoninergic receptors (5-HT6Rs) is highly expressed in the hippocampus, and evidence indicates the beneficial effects of 5-HT6Rs blockade on short- and long-term memory in rodents. Nevertheless, the underlying functional mechanisms still need to be established. To this end, we performed electrophysiological extracellular recordings to assess the effects of the 5-HT6Rs antagonist SB-271046 on the synaptic activity and functional plasticity at the CA3\/CA1 hippocampal connections of male and female mice slices. We found that basal excitatory synaptic transmission and isolated N-methyl-D-aspartate receptors (NMDARs) activation were significantly increased by SB-271046. The NMDARs-related improvement was prevented by the GABAAR antagonist bicuculline in male but not in female mice. Regarding synaptic plasticity, neither paired-pulse facilitation (PPF) nor NMDARs-dependent long-term potentiation (LTP) (induced either by high-frequency or theta-burst stimulation) was affected by the 5-HT6Rs blockade. Taken together, our results indicate a sex-dependent 5-HT6Rs effect on synaptic activity at the CA3\/CA1 hippocampal connections through changes in the excitation\/inhibition balance.<\/jats:p>","DOI":"10.3390\/biom13050751","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T02:50:00Z","timestamp":1682563800000},"page":"751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["5-HT6 Receptors Sex-Dependently Modulate Hippocampal Synaptic Activity through GABA Inhibition"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6571-8599","authenticated-orcid":false,"given":"Caroline","family":"Lahogue","sequence":"first","affiliation":[{"name":"Department of Health, UNICAEN, INSERM, COMETE, CYCERON, FHU A<sup>2<\/sup>M<sup>2<\/sup>P, CHU Caen, Normandie Universit\u00e9, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8677-4415","authenticated-orcid":false,"given":"Jean-Marie","family":"Billard","sequence":"additional","affiliation":[{"name":"Department of Health, UNICAEN, INSERM, COMETE, CYCERON, FHU A<sup>2<\/sup>M<sup>2<\/sup>P, CHU Caen, Normandie Universit\u00e9, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4446-4451","authenticated-orcid":false,"given":"Thomas","family":"Freret","sequence":"additional","affiliation":[{"name":"Department of Health, UNICAEN, INSERM, COMETE, CYCERON, FHU A<sup>2<\/sup>M<sup>2<\/sup>P, CHU Caen, Normandie Universit\u00e9, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0857-2295","authenticated-orcid":false,"given":"Valentine","family":"Bouet","sequence":"additional","affiliation":[{"name":"Department of Health, UNICAEN, INSERM, COMETE, CYCERON, FHU A<sup>2<\/sup>M<sup>2<\/sup>P, CHU Caen, Normandie Universit\u00e9, 14000 Caen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1006\/bbrc.1993.1619","article-title":"A Novel Rat Serotonin (5-HT6) Receptor: Molecular Cloning, Localization and Stimulation of CAMP Accumulation","volume":"193","author":"Ruat","year":"1993","journal-title":"Biochem. 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