{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:57:33Z","timestamp":1781074653271,"version":"3.54.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The orbitofrontal cortex (OFC) and hippocampus are critically involved in cognitive and affective functions. However, the circuit architecture and functional organization linking the OFC with distinct hippocampal subregions, particularly dorsal CA1 (dCA1) and ventral CA1 (vCA1), remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We combined viral circuit tracing with a bilateral disconnection strategy to investigate the anatomical and functional organization of OFC\u2013CA1 connectivity in mice. Dual viral tracing was used to map direct and polysynaptic pathways, and taCasp3-mediated targeted neuronal ablation was employed to assess circuit-specific functional contributions. Behavioral effects were evaluated using spatial memory assays (Y-maze and object location recognition) and emotion-related tests (open field, elevated plus maze, tail suspension, and forced swim tests).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified a unidirectional indirect pathway linking OFC to dCA1 via the claustrum (OFC\u202f\u2192\u202fclaustrum\u2192dCA1), with no evidence of reciprocal dCA1\u202f\u2192\u202fOFC connectivity. In contrast, vCA1 exhibited a distinct connectivity profile, including a direct monosynaptic projection to OFC and multiple indirect pathways through the anterior thalamic nuclei, basolateral amygdala, and entorhinal cortex, while no OFC\u202f\u2192\u202fvCA1 projection was detected. Functionally, disconnection of OFC\u2013dCA1 connectivity selectively impaired spatial memory without affecting anxiety- or depression-like behaviors. Conversely, disconnection of vCA1\u2013OFC connectivity induced anxiety- and depression-like phenotypes while preserving spatial memory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrate that the OFC interacts with dorsal and ventral CA1 subregions through anatomically distinct circuits with dissociable behavioral functions. This study provides circuit-level insight into how OFC\u2013CA1 interactions differentially regulate spatial memory and affect-related behaviors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnbeh.2026.1853168","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T06:03:45Z","timestamp":1781071425000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct orbitofrontal circuits with dorsal and ventral CA1 differentially regulate spatial memory and emotional behaviors"],"prefix":"10.3389","volume":"20","author":[{"given":"Yanling","family":"Liang","sequence":"first","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiran","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zizhuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibing","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nrn3677","article-title":"Hippocampal synaptic plasticity, spatial memory and anxiety","volume":"15","author":"Bannerman","year":"2014","journal-title":"Nat. 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