{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:29:57Z","timestamp":1793204997321,"version":"4.5.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN2020 \u201c2020AMLXHH\u201d"],"award-info":[{"award-number":["PRIN2020 \u201c2020AMLXHH\u201d"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Alpha7 nicotinic acetylcholine receptors (\u03b17-nAChRs) are ionotropic, Ca<jats:sup>2+<\/jats:sup>-permeable receptors highly expressed in brain regions involved in memory formation, such as the hippocampus. Their activation induces cation influx and neuronal depolarization, which in turn promotes glutamate release\u2014highlighting a crucial interplay between cholinergic and glutamatergic signaling in the healthy brain. Interestingly, the genetic deletion of \u03b17-nAChRs in mice (\u03b17-KO mice) leads to an Alzheimer\u2019s disease (AD)-like phenotype characterized by aberrant amyloid-\u03b2 accumulation, tau phosphorylation, and neuroinflammation in aged (&amp;gt;12 months) mice. However, glutamatergic transmission in these mice prior to the onset of the AD-like phenotype has been poorly investigated. We thus studied molecular and functional properties of glutamatergic transmission in 4\u20136-months-old \u03b17-KO mice, representing a prodromal phase of the AD-like neuropathology. We found that hippocampal CA1 neurons in brain slices from \u03b17-KO mice showed a reduced frequency of the spontaneous excitatory post-synaptic currents (sEPSCs) compared to those of wild-type (WT) mice. On the contrary, the amplitude of sEPSCs was not affected, although in \u03b17-KO neurons these currents displayed a longer rise time than in wild-type. CA1 neurons from \u03b17-KO mice also exhibited a significantly smaller evoked NMDA currents than WT neurons, whereas AMPA currents were unaffected. From a molecular point of view, hippocampal neurons of \u03b17-KO mice exhibited an increased expression of the pre-synaptic protein Synapsin-1 and of the NMDA subunits GluN2A and GluN2B, but no modifications in the expression of AMPA receptor subunits (GluA1 and GluA2) were found. Importantly, selective re-expression of the \u03b17-nAChRs in neurons of \u03b17-KO mice restored the evoked NMDA current amplitude and the rise time of sEPSCs, but it did not rescue the frequency of sEPSCs, thus suggesting that post-synaptic integrity depends on neuronal \u03b17-nAChRs.<\/jats:p>","DOI":"10.3389\/fphys.2025.1662171","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T05:27:54Z","timestamp":1754630874000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional deletion of \u03b17 nicotinic acetylcholine receptor impairs Ca2+-dependent glutamatergic synaptic transmission by affecting both presynaptic and postsynaptic protein expression and function"],"prefix":"10.3389","volume":"16","author":[{"given":"Beatrice","family":"Cannata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Sposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Albini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Aceto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Puliatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Lazzarino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Ripoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosaria","family":"Tropea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Puzzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Piacentini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Grassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1007\/s10571-025-01586-6","article-title":"Targeting neuronal Alpha7 nicotinic acetylcholine receptor upregulation in age-related neurological disorders","volume":"45","author":"Abraham","year":"2025","journal-title":"Cell Mol. 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