{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T02:19:08Z","timestamp":1787624348154,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>GPR158 is a G protein coupled receptor (GPCR) that is abundantly expressed in the brain and has been shown to organize synaptic architecture and regulate synaptic function. Previous studies have demonstrated a role for GPR158 in hippocampal\u2010dependent learning and stress\u2010related affective behaviors yet its contribution to cognitive function under naturalistic, low\u2010stress conditions remains unclear. Here, we investigated the role of GPR158 in spatial learning, cognitive flexibility, and working memory using both traditional and automated home\u2010cage paradigms. The use of automated, socially enriched testing paradigms minimizes stress\u2010related confounds and allows us to discover the naturalistic roles of GPR158 in cognition and behavior. Using the IntelliCage to test spatial learning and working memory in a social enriched environment, we found that female GPR158 knockout mice exhibited deficits in spatial learning but showed intact working memory. Consistent with these findings, spatial impairments were also observed in the Barnes Maze, where female GPR158 KO mice showed pronounced deficits in spatial strategy acquisition, increased latency, reduced time spent in the reward area, and impaired performance during the probe trial. Male GPR158 knockout mice showed no significant difference in either spatial learning or working memory compared to their wild\u2010type littermates in the IntelliCage, whereas in the Barnes Maze knockout mice showed mild impairment in spatial strategy acquisition. These findings reveal a profound impairment with female GPR158 knockout mice in hippocampal\u2010dependent cognition and highlight the importance of low\u2010stress, ethologically testing environments.<\/jats:p>","DOI":"10.1111\/gbb.70066","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T10:18:26Z","timestamp":1787048306000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cognitive Deficits in Female\n                    <scp>GPR158<\/scp>\n                    Knockout Mice Revealed by Automated Home\u2010Cage Testing"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9501-8163","authenticated-orcid":false,"given":"Alyson P.","family":"Blount","sequence":"first","affiliation":[{"name":"Department of Biological Sciences University of Maryland Baltimore County  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2940-0656","authenticated-orcid":false,"given":"Shradha V.","family":"Darira","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Maryland Baltimore County  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1612-334X","authenticated-orcid":false,"given":"Emmanuelle B.","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Maryland Baltimore County  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8694-2060","authenticated-orcid":false,"given":"Laurie P.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Maryland Baltimore County  Baltimore Maryland 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