{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:58:51Z","timestamp":1788328731424,"version":"build-2803163510"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"R.L.","award":["T32GM149363"],"award-info":[{"award-number":["T32GM149363"]}]},{"name":"National Institute for Health","award":["R56MH128747"],"award-info":[{"award-number":["R56MH128747"]}]},{"name":"National Institute for Health","award":["R21MH126272"],"award-info":[{"award-number":["R21MH126272"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Beyond its established role in spatial and episodic memory, the dorsal hippocampus also shapes motivated behavior by routing contextual information to downstream targets. Dorsal CA1 (dCA1) projects to the nucleus accumbens (NAc) and lateral septum (LS); here, we show that these pathways regulate distinct behaviors. We mapped and selectively manipulated these circuits in mice using projection-specific viral tracing, intersectional labeling, and terminal optogenetics. Activating dCA1-to-NAc terminals selectively increased social interaction without altering locomotion or novel-object exploration, consistent with a role in social motivation rather than generalized exploration. In contrast, the dCA1-to-LS pathway bidirectionally regulated locomotion, with activation increasing movement and inhibition decreasing locomotion without specifically influencing social behavior. Intersectional labeling also identified a small population of dCA1 neurons that projects to both targets. Together, these findings suggest that distinct dCA1 output pathways can differentially regulate social interaction and locomotor state, providing a circuit-level view of how hippocampal contextual signals are routed to subcortical regions.<\/jats:p>","DOI":"10.1093\/cercor\/bhag059","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T11:32:34Z","timestamp":1776771154000},"source":"Crossref","is-referenced-by-count":1,"title":["Dorsal CA1 projections to nucleus accumbens and lateral septum differentially regulate social and locomotor behavior"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4687-7193","authenticated-orcid":false,"given":"Ye","family":"Han","sequence":"first","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center , 1161 21st Avenue South, Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gai-Linn","family":"Besing","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center , 1161 21st Avenue South, Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachelle","family":"Larivee","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center , 1161 21st Avenue South, Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Y","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , 100 York Street, New Haven, CT 06520 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snigdha","family":"Mukerjee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University , 2222 Pierce Ave, Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty R","family":"Erickson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University , 2222 Pierce Ave, Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center , 1161 21st Avenue South, Nashville, TN 37232 ,","place":["United States"]},{"name":"Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center , 1601 23rd Ave S, Nashville, TN 37212 ,","place":["United States"]},{"name":"Department of Psychiatry, Albany Medical Center , 43 New Scotland Avenue, Albany, NY 12208 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William P","family":"Nobis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center , 1161 21st Avenue South, Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle A","family":"Lyman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yale School of Medicine , 100 York Street, New Haven, CT 06520 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody A","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University , 2222 Pierce Ave, Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dane M","family":"Chetkovich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center , 1161 21st Avenue South, Nashville, TN 37232 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"2026051903540139600_ref1","doi-asserted-by":"publisher","first-page":"7062","DOI":"10.1038\/ncomms8062","article-title":"Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression","volume":"6","author":"Bagot","year":"2015","journal-title":"Nat Commun"},{"key":"2026051903540139600_ref2","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.neubiorev.2004.03.004","article-title":"Regional dissociations within the hippocampus\u2014memory and anxiety","volume":"28","author":"Bannerman","year":"2004","journal-title":"Neurosci Biobehav Rev"},{"key":"2026051903540139600_ref3","doi-asserted-by":"publisher","first-page":"3196","DOI":"10.1038\/s41467-024-47361-x","article-title":"A hippocampus-accumbens code guides goal-directed appetitive behavior","volume":"15","author":"Barnstedt","year":"2024","journal-title":"Nat Commun"},{"key":"2026051903540139600_ref4","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1126\/science.1210789","article-title":"Empathy and pro-social behavior in rats","volume":"334","author":"Bartal","year":"2011","journal-title":"Science."},{"key":"2026051903540139600_ref5","doi-asserted-by":"publisher","first-page":"8521","DOI":"10.1038\/ncomms9521","article-title":"Theta oscillations regulate the speed of locomotion via a hippocampus to lateral septum pathway","volume":"6","author":"Bender","year":"2015","journal-title":"Nat Commun"},{"key":"2026051903540139600_ref7","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41583-019-0125-5","article-title":"Heterogeneity within classical cell types is the rule: lessons from hippocampal pyramidal neurons","volume":"20","author":"Cembrowski","year":"2019","journal-title":"Nat Rev Neurosci"},{"key":"2026051903540139600_ref8","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.neuron.2015.12.013","article-title":"Spatial gene-expression gradients underlie prominent heterogeneity of CA1 pyramidal neurons","volume":"89","author":"Cembrowski","year":"2016","journal-title":"Neuron."},{"key":"2026051903540139600_ref9","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1016\/j.cell.2018.03.031","article-title":"Dissociable structural and functional hippocampal outputs via distinct subiculum cell classes","volume":"173","author":"Cembrowski","year":"2018","journal-title":"Cell."},{"key":"2026051903540139600_ref10","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.biopsych.2013.09.020","article-title":"Amygdala-ventral pallidum pathway decreases dopamine activity after chronic mild stress in rats","volume":"76","author":"Chang","year":"2014","journal-title":"Biol Psychiatry"},{"key":"2026051903540139600_ref11","doi-asserted-by":"publisher","first-page":"155721","DOI":"10.1101\/2020.06.16.155721","article-title":"Ventral hippocampus-lateral septum circuitry promotes foraging-related memory","author":"D\u00e9carie-Spain","year":"2022","journal-title":"bioRxiv"},{"key":"2026051903540139600_ref12","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nature12518","article-title":"Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin","volume":"501","author":"D\u00f6len","year":"2013","journal-title":"Nature."},{"key":"2026051903540139600_ref13","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.neuron.2009.11.031","article-title":"Are the dorsal and ventral hippocampus functionally distinct structures?","volume":"65","author":"Fanselow","year":"2010","journal-title":"Neuron."},{"key":"2026051903540139600_ref14","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1038\/nmeth.2996","article-title":"Targeting cells with single vectors using multiple-feature Boolean logic","volume":"11","author":"Fenno","year":"2014","journal-title":"Nat Methods"},{"key":"2026051903540139600_ref15","doi-asserted-by":"publisher","first-page":"4915","DOI":"10.1523\/jneurosci.21-13-04915.2001","article-title":"Glutamatergic afferents from the hippocampus to the nucleus accumbens regulate activity of ventral tegmental area dopamine neurons","volume":"21","author":"Floresco","year":"2001","journal-title":"J Neurosci"},{"key":"2026051903540139600_ref16","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1038\/s41593-020-0705-8","article-title":"Circuit and molecular architecture of a ventral hippocampal network","volume":"23","author":"Gergues","year":"2020","journal-title":"Nat Neurosci"},{"key":"2026051903540139600_ref17","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1016\/j.cell.2014.05.017","article-title":"Natural neural projection dynamics underlying social behavior","volume":"157","author":"Gunaydin","year":"2014","journal-title":"Cell."},{"key":"2026051903540139600_ref18","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.nlm.2004.03.005","article-title":"On the delay-dependent involvement of the hippocampus in object recognition memory","volume":"82","author":"Hammond","year":"2004","journal-title":"Neurobiol Learn Mem"},{"key":"2026051903540139600_ref19","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1038\/mp.2016.99","article-title":"HCN-channel dendritic targeting requires bipartite interaction with TRIP8b and regulates antidepressant-like behavioral effects","volume":"22","author":"Han","year":"2017","journal-title":"Mol Psychiatry"},{"key":"2026051903540139600_ref20","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1038\/s41467-024-44836-9","article-title":"Dorsal hippocampus to nucleus accumbens projections drive reinforcement via activation of accumbal dynorphin neurons","volume":"15","author":"Ibrahim","year":"2024","journal-title":"Nat Commun"},{"key":"2026051903540139600_ref21","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1016\/j.neubiorev.2003.11.015","article-title":"Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning","volume":"27","author":"Kelley","year":"2004","journal-title":"Neurosci Biobehav Rev"},{"key":"2026051903540139600_ref22","doi-asserted-by":"publisher","first-page":"10825","DOI":"10.1073\/pnas.152112399","article-title":"Reduced fear expression after lesions of the ventral hippocampus","volume":"99","author":"Kjelstrup","year":"2002","journal-title":"Proc Natl Acad Sci"},{"key":"2026051903540139600_ref23","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/s41586-018-0740-8","article-title":"Reward behaviour is regulated by the strength of hippocampus\u2013nucleus accumbens synapses","volume":"564","author":"LeGates","year":"2018","journal-title":"Nature."},{"key":"2026051903540139600_ref24","doi-asserted-by":"publisher","first-page":"7424","DOI":"10.1523\/jneurosci.0936-11.2011","article-title":"Deletion of the hyperpolarization-activated cyclic nucleotide-gated channel auxiliary subunit TRIP8b impairs hippocampal Ih localization and function and promotes antidepressant behavior in mice","volume":"31","author":"Lewis","year":"2011","journal-title":"J Neurosci"},{"key":"2026051903540139600_ref25","doi-asserted-by":"publisher","first-page":"eabl4580","DOI":"10.1126\/scitranslmed.abl4580","article-title":"Hippocampal cAMP regulates HCN channel function on two time scales with differential effects on animal behavior","volume":"13","author":"Lyman","year":"2021","journal-title":"Sci Transl Med"},{"key":"2026051903540139600_ref26","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.tins.2021.10.010","article-title":"Neurobiology of the lateral septum: regulation of social behavior","volume":"45","author":"Menon","year":"2022","journal-title":"Trends Neurosci"},{"key":"2026051903540139600_ref27","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1002\/(sici)1098-1063(1998)8:6&lt;608::aid-hipo3&gt;3.0.co;2-7","article-title":"Functional differentiation in the hippocampus","volume":"8","author":"Moser","year":"1998","journal-title":"Hippocampus."},{"key":"2026051903540139600_ref28","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.biopsych.2020.05.021","article-title":"Ventral-hippocampal afferents to nucleus accumbens encode both latent vulnerability and stress-induced susceptibility","volume":"88","author":"Muir","year":"2020","journal-title":"Biol Psychiatry"},{"key":"2026051903540139600_ref29","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1126\/science.aaf7003","article-title":"Ventral CA1 neurons store social memory","volume":"353","author":"Okuyama","year":"2016","journal-title":"Science."},{"key":"2026051903540139600_ref30","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1101\/lm.051797.120","article-title":"Hippocampal efferents to retrosplenial cortex and lateral septum are required for memory acquisition","volume":"27","author":"Opalka","year":"2020","journal-title":"Learn Memory"},{"key":"2026051903540139600_ref31","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1038\/npp.2017.56","article-title":"Bidirectional control of anxiety-related behaviors in mice: role of inputs arising from the ventral hippocampus to the lateral septum and medial prefrontal cortex","volume":"42","author":"Parfitt","year":"2017","journal-title":"Neuropsychopharmacology."},{"key":"2026051903540139600_ref32","doi-asserted-by":"publisher","first-page":"e3002722","DOI":"10.1371\/journal.pbio.3002722","article-title":"Ventral hippocampus to nucleus accumbens shell circuit regulates approach decisions during motivational conflict","volume":"23","author":"Patterson","year":"2025","journal-title":"PLoS Biol"},{"key":"2026051903540139600_ref33","doi-asserted-by":"publisher","first-page":"16865","DOI":"10.1523\/jneurosci.2449-13.2013","article-title":"The infralimbic cortex bidirectionally modulates mesolimbic dopamine neuron activity via distinct neural pathways","volume":"33","author":"Patton","year":"2013","journal-title":"J Neurosci"},{"key":"2026051903540139600_ref34","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1038\/s41380-020-0686-8","article-title":"Cooperative synaptic and intrinsic plasticity in a disynaptic limbic circuit drive stress-induced anhedonia and passive coping in mice","volume":"26","author":"Pignatelli","year":"2021","journal-title":"Mol Psychiatry"},{"key":"2026051903540139600_ref35","doi-asserted-by":"publisher","first-page":"582638","DOI":"10.1101\/2024.02.28.582638","article-title":"A ventral hippocampal-lateral septum pathway regulates social novelty preference","author":"Rashid","year":"2024","journal-title":"bioRxiv"},{"key":"2026051903540139600_ref36","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1126\/science.272.5267.1484","article-title":"Structural evidence for functional domains in the rat hippocampus","volume":"272","author":"Risold","year":"1996","journal-title":"Science."},{"key":"2026051903540139600_ref37","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/s0165-0173(97)00009-x","article-title":"Connections of the rat lateral septal complex","volume":"24","author":"Risold","year":"1997","journal-title":"Brain Res Rev"},{"key":"2026051903540139600_ref38","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.brainresrev.2004.04.009","article-title":"Regulation of affect by the lateral septum: implications for neuropsychiatry","volume":"46","author":"Sheehan","year":"2004","journal-title":"Brain Res Rev"},{"key":"2026051903540139600_ref39","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1016\/j.neuron.2018.04.015","article-title":"Cocaine place conditioning strengthens location-specific hippocampal coupling to the nucleus accumbens","volume":"98","author":"Sjulson","year":"2018","journal-title":"Neuron."},{"key":"2026051903540139600_ref40","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1038\/s41593-018-0118-0","article-title":"CA1 pyramidal cell diversity enabling parallel information processing in the hippocampus","volume":"21","author":"Soltesz","year":"2018","journal-title":"Nat Neurosci"},{"key":"2026051903540139600_ref41","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.neuron.2019.11.022","article-title":"Dorsal and ventral hippocampal sharp-wave ripples activate distinct nucleus accumbens networks","volume":"105","author":"Sosa","year":"2019","journal-title":"Neuron"},{"key":"2026051903540139600_ref42","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1038\/nrn3785","article-title":"Functional organization of the hippocampal longitudinal axis","volume":"15","author":"Strange","year":"2014","journal-title":"Nat Rev Neurosci"},{"key":"2026051903540139600_ref43","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/j.neuron.2018.04.028","article-title":"Transformation of a spatial map across the hippocampal-lateral septal circuit","volume":"98","author":"Tingley","year":"2018","journal-title":"Neuron."},{"key":"2026051903540139600_ref44","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1016\/j.cell.2018.12.037","article-title":"A hippocampus-accumbens tripartite neuronal motif guides appetitive memory in space","volume":"176","author":"Trouche","year":"2019","journal-title":"Cell."},{"key":"2026051903540139600_ref45","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/nature11740","article-title":"Dopamine neurons modulate neural encoding and expression of depression-related behaviour","volume":"493","author":"Tye","year":"2013","journal-title":"Nature."},{"key":"2026051903540139600_ref6","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/nrn2614","article-title":"The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network","volume":"10","author":"Van","year":"2009","journal-title":"Nat Rev Neurosci"},{"key":"2026051903540139600_ref46","doi-asserted-by":"publisher","first-page":"3177","DOI":"10.1016\/j.cub.2019.07.089","article-title":"Locomotor and hippocampal processing converge in the lateral septum","volume":"29","author":"Wirtshafter","year":"2019","journal-title":"Curr Biol"},{"key":"2026051903540139600_ref47","doi-asserted-by":"publisher","first-page":"e55252","DOI":"10.7554\/elife.55252","article-title":"Differences in reward biased spatial representations in the lateral septum and hippocampus","volume":"9","author":"Wirtshafter","year":"2020","journal-title":"eLife."},{"key":"2026051903540139600_ref48","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1016\/j.celrep.2017.05.047","article-title":"Dorsal-CA1 hippocampal neuronal ensembles encode nicotine-reward contextual associations","volume":"19","author":"Xia","year":"2017","journal-title":"Cell Rep"},{"key":"2026051903540139600_ref49","doi-asserted-by":"publisher","first-page":"3222","DOI":"10.1016\/j.cell.2021.04.021","article-title":"A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation","volume":"184","author":"Yao","year":"2021","journal-title":"Cell."}],"container-title":["Cerebral Cortex"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cercor\/article-pdf\/36\/5\/bhag059\/68332702\/bhag059.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cercor\/article-pdf\/36\/5\/bhag059\/68332702\/bhag059.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:54:07Z","timestamp":1779177247000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cercor\/article\/doi\/10.1093\/cercor\/bhag059\/8687188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,13]]}},"URL":"https:\/\/doi.org\/10.1093\/cercor\/bhag059","relation":{},"ISSN":["1047-3211","1460-2199"],"issn-type":[{"value":"1047-3211","type":"print"},{"value":"1460-2199","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2026,5]]},"article-number":"bhag059"}}