{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T17:08:04Z","timestamp":1776272884982,"version":"3.50.1"},"posted":{"date-parts":[[2024,8,6]]},"group-title":"Neuroscience","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,8,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Social memory impairments in\n                  <jats:italic>Mecp2<\/jats:italic>\n                  knockout (KO) mice result from altered neuronal activity in the monosynaptic projection from the ventral hippocampus (vHIP) to the medial prefrontal cortex (mPFC). The hippocampal network is hyperactive in this model for Rett syndrome, and such atypically heightened neuronal activity propagates to the mPFC through this monosynaptic projection, resulting in altered mPFC network activity and social memory deficits. However, the underlying mechanism of cellular dysfunction within this projection between vHIP pyramidal neurons (PYR) and mPFC PYRs and parvalbumin interneurons (PV-IN) resulting in social memory impairments in\n                  <jats:italic>Mecp2<\/jats:italic>\n                  KO mice has yet to be elucidated. We confirmed\n                  <jats:italic>social memory<\/jats:italic>\n                  (but not\n                  <jats:italic>sociability<\/jats:italic>\n                  ) deficits in\n                  <jats:italic>Mecp2<\/jats:italic>\n                  KO mice using a new 4-chamber social memory arena, designed to minimize the impact of the tethering to optical fibers required for simultaneous\n                  <jats:italic>in vivo<\/jats:italic>\n                  fiber photometry of Ca\n                  <jats:sup>2+<\/jats:sup>\n                  -sensor signals during social interactions. mPFC PYRs of wildtype (WT) mice showed increases in Ca\n                  <jats:sup>2+<\/jats:sup>\n                  signal amplitude during explorations of a novel toy mouse and interactions with both familiar and novel mice, while PYRs of\n                  <jats:italic>Mecp2<\/jats:italic>\n                  KO mice showed smaller Ca\n                  <jats:sup>2+<\/jats:sup>\n                  signals during interactions only with live mice. On the other hand, mPFC PV-INs of\n                  <jats:italic>Mecp2<\/jats:italic>\n                  KO mice showed larger Ca\n                  <jats:sup>2+<\/jats:sup>\n                  signals during interactions with a familiar cage-mate compared to those signals in PYRs, a difference absent in the WT mice. These observations suggest atypically heightened inhibition and impaired excitation in the mPFC network of\n                  <jats:italic>Mecp2<\/jats:italic>\n                  KO mice during social interactions, potentially driving their deficit in social memory.\n                <\/jats:p>","DOI":"10.1101\/2024.08.06.606882","type":"posted-content","created":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T04:00:24Z","timestamp":1723003224000},"source":"Crossref","is-referenced-by-count":1,"title":["Altered activity of mPFC pyramidal neurons and parvalbumin-expressing interneurons during social interactions in a\n                  <i>Mecp2<\/i>\n                  mouse model for Rett syndrome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1871-4189","authenticated-orcid":false,"given":"Destynie","family":"Medeiros","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0941-9289","authenticated-orcid":false,"given":"Likhitha","family":"Polepalli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3232-8986","authenticated-orcid":false,"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6085-5527","authenticated-orcid":false,"given":"Lucas","family":"Pozzo-Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024080803451339000_2024.08.06.606882v1.1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2013.00002"},{"key":"2024080803451339000_2024.08.06.606882v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"2024080803451339000_2024.08.06.606882v1.3","doi-asserted-by":"publisher","DOI":"10.1177\/08830738050200082401"},{"key":"2024080803451339000_2024.08.06.606882v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-018-5187-5"},{"key":"2024080803451339000_2024.08.06.606882v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14740-z"},{"key":"2024080803451339000_2024.08.06.606882v1.6","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh142"},{"key":"2024080803451339000_2024.08.06.606882v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.213"},{"key":"2024080803451339000_2024.08.06.606882v1.8","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00800.2010"},{"key":"2024080803451339000_2024.08.06.606882v1.9","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22360"},{"key":"2024080803451339000_2024.08.06.606882v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.10.001"},{"key":"2024080803451339000_2024.08.06.606882v1.11","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.neuron.2018.02.026","article-title":"Neural Circuit Mechanisms of Social Behavior","volume":"98","year":"2018","journal-title":"Neuron"},{"key":"2024080803451339000_2024.08.06.606882v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/85906"},{"key":"2024080803451339000_2024.08.06.606882v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2018.01.019"},{"key":"2024080803451339000_2024.08.06.606882v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.12.018"},{"key":"2024080803451339000_2024.08.06.606882v1.15","doi-asserted-by":"crossref","unstructured":"Dana, H. , Mohar, B. , Sun, Y. , Narayan, S. , Gordus, A. , Hasseman, J. P. , Tsegaye, G. , Holt, G. T. , Hu, A. , Walpita, D. et al. (2016). Sensitive red protein calcium indicators for imaging neural activity. Elife 5.","DOI":"10.7554\/eLife.12727"},{"key":"2024080803451339000_2024.08.06.606882v1.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506071102"},{"key":"2024080803451339000_2024.08.06.606882v1.17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4673-14.2015"},{"key":"2024080803451339000_2024.08.06.606882v1.18","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2013.00042"},{"key":"2024080803451339000_2024.08.06.606882v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.12.004"},{"key":"2024080803451339000_2024.08.06.606882v1.20","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181d6b852"},{"key":"2024080803451339000_2024.08.06.606882v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.05.017"},{"key":"2024080803451339000_2024.08.06.606882v1.22","doi-asserted-by":"publisher","DOI":"10.1177\/088307388800300102"},{"key":"2024080803451339000_2024.08.06.606882v1.23","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410140412"},{"key":"2024080803451339000_2024.08.06.606882v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/nature13028"},{"key":"2024080803451339000_2024.08.06.606882v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-79109-0"},{"key":"2024080803451339000_2024.08.06.606882v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2009.04.017"},{"key":"2024080803451339000_2024.08.06.606882v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3770"},{"key":"2024080803451339000_2024.08.06.606882v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.014"},{"key":"2024080803451339000_2024.08.06.606882v1.29","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2017.00041"},{"key":"2024080803451339000_2024.08.06.606882v1.30","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2016.00151"},{"key":"2024080803451339000_2024.08.06.606882v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.10.037"},{"key":"2024080803451339000_2024.08.06.606882v1.32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41684-022-00919-y","article-title":"New insights into Rett syndrome","volume":"51","year":"2022","journal-title":"Lab Anim (NY)"},{"key":"2024080803451339000_2024.08.06.606882v1.33","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0307-16.2016"},{"key":"2024080803451339000_2024.08.06.606882v1.34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1517244113"},{"key":"2024080803451339000_2024.08.06.606882v1.35","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.neuron.2018.08.043","article-title":"Distinct and Dynamic ON and OFF Neural Ensembles in the Prefrontal Cortex Code Social Exploration","volume":"100","year":"2018","journal-title":"Neuron"},{"key":"2024080803451339000_2024.08.06.606882v1.36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1616-12.2012"},{"key":"2024080803451339000_2024.08.06.606882v1.37","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay4073"},{"key":"2024080803451339000_2024.08.06.606882v1.38","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0378-18.2018"},{"key":"2024080803451339000_2024.08.06.606882v1.39","doi-asserted-by":"crossref","unstructured":"Liu, X. , Dimidschstein, J. , Fishell, G. and Carter, A. G . (2020b). Hippocampal inputs engage CCK+ interneurons to mediate endocannabinoid-modulated feed-forward inhibition in the prefrontal cortex. Elife 9.","DOI":"10.7554\/eLife.55267"},{"key":"2024080803451339000_2024.08.06.606882v1.40","first-page":"7","article-title":"Bonsai: an event-based framework for processing and controlling data streams","volume":"9","year":"2015","journal-title":"Front Neuroinform"},{"key":"2024080803451339000_2024.08.06.606882v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0073-9"},{"key":"2024080803451339000_2024.08.06.606882v1.42","doi-asserted-by":"crossref","unstructured":"Martianova, E. , Aronson, S. and Proulx, C. D . (2019). Multi-Fiber Photometry to Record Neural Activity in Freely-Moving Animals. J Vis Exp.","DOI":"10.3791\/60278-v"},{"key":"2024080803451339000_2024.08.06.606882v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06501-w"},{"key":"2024080803451339000_2024.08.06.606882v1.44","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22797"},{"key":"2024080803451339000_2024.08.06.606882v1.45","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-1848.2004.00076.x"},{"key":"2024080803451339000_2024.08.06.606882v1.46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2004.00071.x"},{"key":"2024080803451339000_2024.08.06.606882v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.03.051"},{"key":"2024080803451339000_2024.08.06.606882v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2017.05.007"},{"key":"2024080803451339000_2024.08.06.606882v1.49","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf7003"},{"key":"2024080803451339000_2024.08.06.606882v1.50","doi-asserted-by":"crossref","unstructured":"Phillips, M. L. , Robinson, H. A. and Pozzo-Miller, L . (2019). Ventral hippocampal projections to the medial prefrontal cortex regulate social memory. Elife 8.","DOI":"10.7554\/eLife.44182"},{"key":"2024080803451339000_2024.08.06.606882v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.11.036"},{"key":"2024080803451339000_2024.08.06.606882v1.52","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds406"},{"key":"2024080803451339000_2024.08.06.606882v1.53","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhv002"},{"key":"2024080803451339000_2024.08.06.606882v1.54","doi-asserted-by":"crossref","unstructured":"Selimbeyoglu, A. , Kim, C. K. , Inoue, M. , Lee, S. Y. , Hong, A. S. O. , Kauvar, I. , Ramakrishnan, C. , Fenno, L. E. , Davidson, T. J. , Wright, M. et al. (2017). Modulation of prefrontal cortex excitation\/inhibition balance rescues social behavior in CNTNAP2-deficient mice. Sci Transl Med 9.","DOI":"10.1126\/scitranslmed.aah6733"},{"key":"2024080803451339000_2024.08.06.606882v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1209"},{"key":"2024080803451339000_2024.08.06.606882v1.56","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-018-0480-0"},{"key":"2024080803451339000_2024.08.06.606882v1.57","doi-asserted-by":"crossref","first-page":"100894","DOI":"10.1016\/j.isci.2020.100894","article-title":"Ventral Hippocampal-Prefrontal Interaction Affects Social Behavior via Parvalbumin Positive Neurons in the Medial Prefrontal Cortex","volume":"23","year":"2020","journal-title":"iScience"},{"key":"2024080803451339000_2024.08.06.606882v1.58","doi-asserted-by":"crossref","first-page":"113850","DOI":"10.1016\/j.celrep.2024.113850","article-title":"Engram reactivation mimics cellular signatures of fear","volume":"43","year":"2024","journal-title":"Cell Rep"},{"key":"2024080803451339000_2024.08.06.606882v1.59","doi-asserted-by":"crossref","unstructured":"Tao, K. , Chung, M. , Watarai, A. , Huang, Z. , Wang, M. Y. and Okuyama, T . (2022). Disrupted social memory ensembles in the ventral hippocampus underlie social amnesia in autism-associated Shank3 mutant mice. Mol Psychiatry.","DOI":"10.1101\/2021.06.25.449869"},{"key":"2024080803451339000_2024.08.06.606882v1.60","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/j.jmb.2019.10.004","article-title":"The Molecular Basis of MeCP2 Function in the Brain","volume":"432","year":"2020","journal-title":"J Mol Biol"},{"key":"2024080803451339000_2024.08.06.606882v1.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2018.01.015"},{"key":"2024080803451339000_2024.08.06.606882v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31578-9"},{"key":"2024080803451339000_2024.08.06.606882v1.63","doi-asserted-by":"crossref","unstructured":"Yang, M. , Silverman, J. L. and Crawley, J. N . (2011). Automated three-chambered social approach task for mice. Curr Protoc Neurosci Chapter 8, Unit 8 26.","DOI":"10.1002\/0471142301.ns0826s56"},{"key":"2024080803451339000_2024.08.06.606882v1.64","doi-asserted-by":"publisher","DOI":"10.1038\/nature10360"},{"key":"2024080803451339000_2024.08.06.606882v1.65","doi-asserted-by":"crossref","first-page":"eabf7467","DOI":"10.1126\/sciadv.abf7467","article-title":"Motor training improves coordination and anxiety in symptomatic Mecp2-null mice despite impaired functional connectivity within the motor circuit","volume":"7","year":"2021","journal-title":"Sci Adv"},{"key":"2024080803451339000_2024.08.06.606882v1.66","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20389"},{"key":"2024080803451339000_2024.08.06.606882v1.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05828-9"},{"key":"2024080803451339000_2024.08.06.606882v1.68","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo4884"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.08.06.606882","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:49:10Z","timestamp":1768459750000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.08.06.606882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,6]]},"references-count":68,"URL":"https:\/\/doi.org\/10.1101\/2024.08.06.606882","relation":{},"subject":[],"published":{"date-parts":[[2024,8,6]]},"subtype":"preprint"}}