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Despite the knowledge of this vulnerability, the mechanisms underlying it are still poorly understood. Excitatory afferents to the nucleus accumbens (NAc) mediate responses to both stressful and rewarding stimuli. Understanding how adolescent social isolation alters these afferents could inform the development of targeted interventions both before and after drug use. Here, we used social isolation rearing as a model of early life adversity which we have previously demonstrated increases vulnerability to cocaine addiction\u2010like behaviour. The current study examined the effect of social isolation rearing on presynaptic glutamatergic transmission in NAc medium spiny neurons in both male and female mice. We show that social isolation rearing alters presynaptic plasticity in the NAc by decreasing the paired\u2010pulse ratio and the size of the readily releasable pool of glutamate. Optogenetically activating the glutamatergic input from the ventral hippocampus to the NAc is sufficient to recapitulate the decreases in paired\u2010pulse ratio and readily releasable pool size seen following electrical stimulation of all NAc afferents. Further, optogenetically inhibiting the ventral hippocampal afferent during electrical stimulation eliminates the effect of early life adversity on the paired\u2010pulse ratio or readily releasable pool size. In summary, we demonstrate that social isolation rearing leads to alterations in glutamate transmission driven by projections from the ventral hippocampus. These data suggest that targeting the circuit from the ventral hippocampus to the nucleus accumbens could provide a means to reverse stress\u2010induced plasticity.<\/jats:p>","DOI":"10.1111\/adb.13077","type":"journal-article","created":{"date-parts":[[2021,7,18]],"date-time":"2021-07-18T21:47:15Z","timestamp":1626644835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Adolescent social isolation induced alterations in nucleus accumbens glutamate signalling"],"prefix":"10.1111","volume":"27","author":[{"given":"Andre U.","family":"Deutschmann","sequence":"first","affiliation":[{"name":"Department of Psychology Temple University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M.","family":"Kirkland","sequence":"additional","affiliation":[{"name":"Department of Psychology Temple University  Philadelphia Pennsylvania 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