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They have been proposed as potential targets to restore excitatory\/inhibitory balance in acute amyloidosis models, where hyperexcitability is a hallmark. However, the role of GIRK signaling in transgenic mice models of Alzheimer\u2019s disease (AD) is largely unknown. Here, we study whether progressive amyloid-\u03b2 (A\u03b2) accumulation in the hippocampus during aging alters GIRK channel expression in mutant \u03b2-amyloid precursor protein (APPSw,Ind J9) transgenic AD mice. Additionally, we examine the impact of spatial memory training in a hippocampal-dependent task, on protein expression of GIRK subunits and Regulator of G-protein signaling 7 (RGS7) in the hippocampus of APPSw,Ind J9 mice. Firstly, we found a reduction in GIRK2 expression (the main neuronal GIRK channels subunit) in the hippocampus of 6-month-old APPSw,Ind J9 mice. Moreover, we found an aging effect on GIRK2 and GIRK3 subunits in both wild type (WT) and APPSw,Ind J9 mice. Finally, when 6-month-old animals were challenged to a spatial memory training, GIRK2 expression in the APPSw,Ind J9 mice were normalized to WT levels. Together, our results support the evidence that GIRK2 could account for the excitatory\/inhibitory neurotransmission imbalance found in AD models, and training in a cognitive hippocampal dependent task may have therapeutic benefits of reversing this effect and lessen early AD deficits.<\/jats:p>","DOI":"10.3390\/ijms232113444","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T03:28:10Z","timestamp":1667532490000},"page":"13444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Spatial Memory Training Counteracts Hippocampal GIRK Channel Decrease in the Transgenic APPSw,Ind J9 Alzheimer\u2019s Disease Mouse Model"],"prefix":"10.3390","volume":"23","author":[{"given":"Sara","family":"Temprano-Carazo","sequence":"first","affiliation":[{"name":"Neurophysiology & Behavior Lab, Centro Regional de Investigaciones Biom\u00e9dicas (CRIB), School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13079 Ciudad Real, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2185-0851","authenticated-orcid":false,"given":"Ana","family":"Contreras","sequence":"additional","affiliation":[{"name":"Neurophysiology & Behavior Lab, Centro Regional de Investigaciones Biom\u00e9dicas (CRIB), School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13079 Ciudad Real, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3692-5657","authenticated-orcid":false,"given":"Carlos A.","family":"Saura","sequence":"additional","affiliation":[{"name":"Institut de Neuroci\u00e8ncies, Department de Bioqu\u00edmica i Biolog\u00eda Molecular, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1877-7833","authenticated-orcid":false,"given":"Juan D.","family":"Navarro-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Neurophysiology & Behavior Lab, Centro Regional de Investigaciones Biom\u00e9dicas (CRIB), School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13079 Ciudad Real, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9121-0334","authenticated-orcid":false,"given":"Lydia","family":"Jim\u00e9nez-D\u00edaz","sequence":"additional","affiliation":[{"name":"Neurophysiology & Behavior Lab, Centro Regional de Investigaciones Biom\u00e9dicas (CRIB), School of Medicine of Ciudad Real, University of Castilla-La Mancha, 13079 Ciudad Real, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"ref_1","unstructured":"Gauthier, S., Rosa-Neto, P., Morais, J.A., and Webster, C. 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