{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T06:23:46Z","timestamp":1787207026680,"version":"build-2736575974"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"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>Introduction<\/jats:title>\n                    <jats:p>Oxytocin (OXT) has emerged as a key neuromodulator of social cognition, yet the precise neural circuits underlying its role in social memory remain poorly defined. In this study, we identify a specific mechanism by which OXT regulates social memory encoding through the lateral entorhinal cortex (LEC), a critical gateway to the hippocampus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using whole-cell patch-clamp recordings in mouse brain slices, we examined the effects of OXT on stellate neurons in the superficial layers of the LEC. Behavioral analyses were performed to determine the role of intra-LEC OXT signaling in the encoding and retrieval of social memory. Pharmacological blockade of OXTRs in the LEC was used to assess its effects on social recognition memory and spatial memory performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>OXT excited stellate neurons in the superficial layers of the LEC via activation of oxytocin receptors (OXTRs). This excitation was mediated by membrane depolarization and enhanced excitatory synaptic transmission, as evidenced by an increased amplitude of miniature excitatory postsynaptic currents. Intra-LEC OXT signaling was essential for the encoding, but not the retrieval, of social memory. Pharmacological blockade of OXTRs in the LEC selectively impaired social recognition memory without affecting spatial memory performance. Furthermore, inhibition of OXTRs during the recall phase did not disrupt memory expression, indicating a specific role in memory formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings establish the LEC as a critical node for OXT-dependent modulation of social memory and suggest that OXT enhances the flow of social information to the hippocampus via direct excitation of LEC stellate neurons. This circuit-specific action provides a mechanistic basis for the selective influence of OXT on social cognition and highlights the LEC\u2013hippocampal pathway as a potential target for therapeutic intervention in social memory deficits associated with neuropsychiatric disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnbeh.2026.1834610","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:28:15Z","timestamp":1787203695000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Oxytocin specifically participates in social memory encoding by exciting stellate neurons in the lateral entorhinal cortex"],"prefix":"10.3389","volume":"20","author":[{"given":"Jinquan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Chongqing Liangjiang New Area Traditional Chinese Medicine Hospital","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Cai","sequence":"additional","affiliation":[{"name":"927th Hospital of Joint Logistics Support Force, PLA","place":["Pu\u2019er, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, General Hospital of Tibet Military Command","place":["Lhasa, Tibet, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijian","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, General Hospital of Tibet Military Command","place":["Lhasa, Tibet, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"927th Hospital of Joint Logistics Support Force, PLA","place":["Pu\u2019er, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Wang","sequence":"additional","affiliation":[{"name":"927th Hospital of Joint Logistics Support Force, PLA","place":["Pu\u2019er, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxiang","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Southwest Hospital, Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, General Hospital of Tibet Military Command","place":["Lhasa, Tibet, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Chongqing Liangjiang New Area Traditional Chinese Medicine Hospital","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1002\/hipo.22529","article-title":"Two distinct types of depolarizing after potentials are differentially expressed in stellate and pyramidal-like neurons of entorhinal-cortex layer II","volume":"26","author":"Alessi","year":"2016","journal-title":"Hippocampus"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/s41398-024-02955-3","article-title":"Social interaction-induced fear memory reduction: exploring the influence of dopamine and oxytocin receptors on memory updating","volume":"14","author":"Arellano Perez","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1093\/cercor\/bhx145","article-title":"Histamine enhances Theta-coupled spiking and gamma oscillations in the medial entorhinal cortex consistent with successful spatial recognition","volume":"28","author":"Chen","year":"2018","journal-title":"Cereb. Cortex"},{"key":"ref4","article-title":"Simultaneous knockouts of the oxytocin and vasopressin 1b receptors in hippocampal CA2 impair social memory","author":"Cymerblit-Sabba","year":"2023","journal-title":"bioRxiv"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf3119","article-title":"Gamma rhythm communication between entorhinal cortex and dentate gyrus neuronal assemblies","volume":"372","author":"Fern\u00e1ndez-Ruiz","year":"2021","journal-title":"Science"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"111604","DOI":"10.1016\/j.brainresbull.2025.111604","article-title":"Oxytocin modulates emotion, learning, and memory: insights from advanced fMRI analysis techniques","volume":"232","author":"Fooladi","year":"2025","journal-title":"Brain Res. Bull."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1111\/j.1528-1167.2011.03337.x","article-title":"Enhanced actions of adenosine in medial entorhinal cortex layer II stellate neurons in temporal lobe epilepsy are mediated via a(1)-receptor activation","volume":"53","author":"Hargus","year":"2012","journal-title":"Epilepsia"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1093\/cercor\/bhu322","article-title":"Superficial layer-specific histaminergic modulation of medial entorhinal cortex required for spatial learning","volume":"26","author":"He","year":"2016","journal-title":"Cereb. Cortex"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/j.neuint.2012.01.030","article-title":"Social memory, amnesia, and autism: brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38","volume":"61","author":"Higashida","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2132","DOI":"10.1002\/hbm.22760","article-title":"Oxytocin selectively facilitates learning with social feedback and increases activity and functional connectivity in emotional memory and reward processing regions","volume":"36","author":"Hu","year":"2015","journal-title":"Hum. Brain Mapp."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1038\/s41593-023-01557-4","article-title":"Lateral entorhinal cortex subpopulations represent experiential epochs surrounding reward","volume":"27","author":"Issa","year":"2024","journal-title":"Nat. Neurosci."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.1177\/13623613211034375","article-title":"Oxytocin levels tend to be lower in autistic children: a meta-analysis of 31 studies","volume":"25","author":"John","year":"2021","journal-title":"Autism"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"eadr0927","DOI":"10.1126\/science.adr0927","article-title":"Event structure sculpts neural population dynamics in the lateral entorhinal cortex","volume":"388","author":"Kanter","year":"2025","journal-title":"Science"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/nature14622","article-title":"Speed cells in the medial entorhinal cortex","volume":"523","author":"Kropff","year":"2015","journal-title":"Nature"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"a054026","DOI":"10.1101\/lm.054026.124","article-title":"Lateral entorhinal cortex neurons that project to nucleus accumbens mediate contextual associative memory","volume":"31","author":"Kuhn","year":"2024","journal-title":"Learn. Mem."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.cell.2016.08.067","article-title":"A cortical circuit for sexually dimorphic oxytocin-dependent anxiety behaviors","volume":"167","author":"Li","year":"2016","journal-title":"Cell"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.cell.2016.12.028","article-title":"Structure of a pancreatic ATP-sensitive potassium channel","volume":"168","author":"Li","year":"2017","journal-title":"Cell"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.neuron.2023.10.012","article-title":"Spatial memory requires hypocretins to elevate medial entorhinal gamma oscillations","volume":"112","author":"Liao","year":"2024","journal-title":"Neuron"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41598-019-51674-z","article-title":"Cage aggression in group-housed laboratory male mice: an international data crowdsourcing project","volume":"9","author":"Lidster","year":"2019","journal-title":"Sci. Rep."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"181","DOI":"10.3389\/fncel.2020.00181","article-title":"Dopamine suppresses synaptic responses of fan cells in the lateral entorhinal cortex to olfactory bulb input in mice","volume":"14","author":"Liu","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.34133\/research.1076","article-title":"Decreased oxytocin mediates PVN-CA2 and PVN-PrL in sleep deprivation-induced social memory deficits","volume":"9","author":"Liu","year":"2026","journal-title":"Research"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"3257","DOI":"10.7150\/thno.109104","article-title":"Oxytocin modulates inhibitory balance in the prelimbic cortex to support social memory consolidation during REM sleep","volume":"15","author":"Liu","year":"2025","journal-title":"Theranostics"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e2529865123","DOI":"10.1073\/pnas.2529865123","article-title":"Post-encoding administration of oxytocin selectively enhances memory consolidation of male faces in females","volume":"123","author":"Liu","year":"2026","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1016\/j.neuron.2022.01.028","article-title":"A direct lateral entorhinal cortex to hippocampal CA2 circuit conveys social information required for social memory","volume":"110","author":"Lopez-Rojas","year":"2022","journal-title":"Neuron"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/j.psyneuen.2012.09.018","article-title":"Oxytocin mediates rodent social memory within the lateral septum and the medial amygdala depending on the relevance of the social stimulus: male juvenile versus female adult conspecifics","volume":"38","author":"Lukas","year":"2013","journal-title":"Psychoneuroendocrinology"},{"key":"ref26","article-title":"Oxytocin enhances excitability and potentiates synaptic transmission in dentate gyrus granule cells","author":"Marron","year":"2025","journal-title":"bioRxiv"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/s41583-023-00759-w","article-title":"Detection, processing and reinforcement of social cues: regulation by the oxytocin system","volume":"24","author":"Menon","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1038\/s41586-020-2758-y","article-title":"Hippocampal CA2 sharp-wave ripples reactivate and promote social memory","volume":"587","author":"Oliva","year":"2020","journal-title":"Nature"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S0304-3940(00)00794-1","article-title":"Hyperpolarization-activated cation currents in stellate and pyramidal neurons of rat entorhinal cortex","volume":"281","author":"Richter","year":"2000","journal-title":"Neurosci. Lett."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"bqac111","DOI":"10.1210\/endocr\/bqac111","article-title":"Oxytocin, vasopressin, and social behavior: from neural circuits to clinical opportunities","volume":"163","author":"Rigney","year":"2022","journal-title":"Endocrinology"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1093\/cvr\/cvs285","article-title":"The inhibition of the potassium channel TASK-1 in rat cardiac muscle by endothelin-1 is mediated by phospholipase C","volume":"97","author":"Schiekel","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e0284962","DOI":"10.1371\/journal.pone.0284962","article-title":"Regulation of the two-pore domain potassium channel, THIK-1 and THIK-2, by G protein coupled receptors","volume":"18","author":"Tateyama","year":"2023","journal-title":"PLoS One"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"114795","DOI":"10.1016\/j.celrep.2024.114795","article-title":"Involvement of a lateral entorhinal cortex engram in episodic-like memory recall","volume":"43","author":"Tozzi","year":"2024","journal-title":"Cell Rep."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/s41586-018-0459-6","article-title":"Integrating time from experience in the lateral entorhinal cortex","volume":"561","author":"Tsao","year":"2018","journal-title":"Nature"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1152\/physrev.00042.2020","article-title":"Microcircuits for spatial coding in the medial entorhinal cortex","volume":"102","author":"Tukker","year":"2022","journal-title":"Physiol. Rev."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1093\/cercor\/bhn114","article-title":"Entorhinal cortex inhibits medial prefrontal cortex and modulates the activity states of electrophysiologically characterized pyramidal neurons in vivo","volume":"19","author":"Valenti","year":"2009","journal-title":"Cereb. Cortex"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1093\/cercor\/bhs033","article-title":"Distinct roles of medial and lateral entorhinal cortex in spatial cognition","volume":"23","author":"Van Cauter","year":"2013","journal-title":"Cereb. Cortex"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"eadp3814","DOI":"10.1126\/science.adp3814","article-title":"Representation of sex-specific social memory in ventral CA1 neurons","volume":"389","author":"Watarai","year":"2025","journal-title":"Science"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1016\/j.jsxm.2018.10.008","article-title":"Cligosiban, a novel brain-penetrant, selective oxytocin receptor antagonist, inhibits ejaculatory physiology in rodents","volume":"15","author":"Wayman","year":"2018","journal-title":"J. Sex. Med."}],"container-title":["Frontiers in Behavioral Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2026.1834610\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:28:16Z","timestamp":1787203696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2026.1834610\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":39,"alternative-id":["10.3389\/fnbeh.2026.1834610"],"URL":"https:\/\/doi.org\/10.3389\/fnbeh.2026.1834610","relation":{},"ISSN":["1662-5153"],"issn-type":[{"value":"1662-5153","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]},"article-number":"1834610"}}