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Here, we show that the vHIP-mPFC projection is hyperactive in the Mecp2 knockout mouse model of the autism spectrum disorder Rett syndrome, which has deficits in social memory. Long-term excitation of mPFC-projecting vHIP neurons in wild-type mice impaired social memory, whereas their long-term inhibition in Rett mice rescued social memory deficits. The extent of social memory improvement was negatively correlated with vHIP-evoked responses in mPFC slices, on a mouse-per-mouse basis. Acute manipulations of the vHIP-mPFC projection affected social memory in a region and behavior selective manner, suggesting that proper vHIP-mPFC signaling is necessary to recall social memories. In addition, we identified an altered pattern of vHIP innervation of mPFC neurons, and increased synaptic strength of vHIP inputs onto layer five pyramidal neurons as contributing factors of aberrant vHIP-mPFC signaling in Rett mice.<\/jats:p>","DOI":"10.7554\/elife.44182","type":"journal-article","created":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T08:00:23Z","timestamp":1558425623000},"source":"Crossref","is-referenced-by-count":215,"title":["Ventral hippocampal projections to the medial prefrontal cortex regulate social memory"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4696-1555","authenticated-orcid":true,"given":"Mary L","family":"Phillips","sequence":"first","affiliation":[{"name":"Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly Anne","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6085-5527","authenticated-orcid":true,"given":"Lucas","family":"Pozzo-Miller","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2019,5,21]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.celrep.2017.12.073","article-title":"Cell-Type specificity of callosally evoked excitation and feedforward inhibition in the prefrontal cortex","volume":"22","author":"Anastasiades","year":"2018","journal-title":"Cell Reports"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"5163","DOI":"10.1073\/pnas.0700293104","article-title":"Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand","volume":"104","author":"Armbruster","year":"2007","journal-title":"PNAS"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1152\/jn.00922.2004","article-title":"Dopamine enhances spatiotemporal spread of activity in rat prefrontal cortex","volume":"93","author":"Bandyopadhyay","year":"2005","journal-title":"Journal of Neurophysiology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1007\/s10339-018-0866-5","article-title":"Social behaviour and social cognition in high-functioning adolescents with autism spectrum disorder (ASD): two sides of the same coin?","volume":"19","author":"Barendse","year":"2018","journal-title":"Cognitive Processing"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"e95392","DOI":"10.1371\/journal.pone.0095392","article-title":"Combined use of the canine adenovirus-2 and DREADD-technology to activate specific neural pathways in vivo","volume":"9","author":"Boender","year":"2014","journal-title":"PLOS ONE"},{"key":"bib6","article-title":"GitHub","author":"Branson","year":"2019","unstructured":"Branson KJ. 2019. 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