biostudies-literature00530Baimel CNIDA NIH HHSNINDS NIH HHSNIHCIHR2256-2263.e3https://www.ebi.ac.uk/biostudies/studies/S-EPMC6733522biostudies-literatureUnknown28(9)We examine synaptic connectivity and cocaine-evoked plasticity at specific networks within the nucleus accumbens (NAc). We identify distinct subpopulations of D1+ medium spiny neurons (MSNs) that project to either the ventral pallidum (D1+^VP) or the ventral tegmental area (D1+^VTA). We show that inputs from the ventral hippocampus (vHPC), but not the basolateral amygdala (BLA), are initially biased onto D1+^VTA MSNs. However, repeated cocaine exposure eliminates the bias of vHPC inputs onto D1+^VTA MSNs, while strengthening BLA inputs onto D1+^VP MSNs. Our results reveal that connectivity and plasticity depend on the specific inputs and outputs of D1+ MSNs and highlight the complexity of cocaine-evoked circuit level adaptations in the NAc.Cell reportsThe Projection Targets of Medium Spiny Neurons Govern Cocaine-Evoked Synaptic Plasticity in the Nucleus Accumbens.PMC6733522R01 DA038138T32 NS086750Baimel CMcGarry LMCarter AG53falseThe Projection Targets of Medium Spiny Neurons Govern Cocaine-Evoked Synaptic Plasticity in the Nucleus Accumbens.We examine synaptic connectivity and cocaine-evoked plasticity at specific networks within the nucleus accumbens (NAc). We identify distinct subpopulations of D1+ medium spiny neurons (MSNs) that project to either the ventral pallidum (D1+^VP) or the ventral tegmental area (D1+^VTA). We show that inputs from the ventral hippocampus (vHPC), but not the basolateral amygdala (BLA), are initially biased onto D1+^VTA MSNs. However, repeated cocaine exposure eliminates the bias of vHPC inputs onto D1+^VTA MSNs, while strengthening BLA inputs onto D1+^VP MSNs. Our results reveal that connectivity and plasticity depend on the specific inputs and outputs of D1+ MSNs and highlight the complexity of cocaine-evoked circuit level adaptations in the NAc.2019-01-01T00:00:00Z2019 Aug2024-11-20T21:15:11.229Z2019-09-13T07:01:23ZS-EPMC67335223146164310.1016/j.celrep.2019.07.074