The Projection Targets of Medium Spiny Neurons Govern Cocaine-Evoked Synaptic Plasticity in the Nucleus Accumbens

• Published in: Cell reports (Cambridge) Vol. 28; no. 9; pp. 2256 - 2263.e3
• Main Authors: Baimel, Corey, McGarry, Laura M., Carter, Adam G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.08.2019; Elsevier
• Subjects: Animals; Cocaine - pharmacology; cocaine sensitization; Dopamine Uptake Inhibitors - pharmacology; Female; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - physiology; Male; medium spiny neuron; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Neurons - drug effects; Neurons - physiology; nucleus accumbens; Nucleus Accumbens - cytology; Nucleus Accumbens - drug effects; Nucleus Accumbens - physiology; spiny projection neuron; synaptic plasticity; Ventral Tegmental Area - cytology; Ventral Tegmental Area - drug effects; Ventral Tegmental Area - physiology; cocaine sensitization; spiny projection neuron; nucleus accumbens; synaptic plasticity; medium spiny neuron
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.07.074

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. [Display omitted] •NAc medial shell has multiple D1 receptor-expressing (D1+) medium spiny neurons (MSNs)•Distinct D1+ MSNs project to ventral tegmental area (VTA) and ventral pallidum (VP)•Hippocampus (vHPC) and amygdala (BLA) differentially target D1+VTA and D1+VP MSNs•Cocaine selectively alters vHPC inputs at D1+VTA MSNs and BLA inputs at D1+VP MSNs Baimel et al. examine how cocaine exposure alters specific circuits in the nucleus accumbens medial shell. They find that D1-expressing (D1+) medium spiny neurons projecting to ventral tegmental area and ventral pallidum are distinct populations. These two cell types differ in both their baseline synaptic connectivity and cocaine-evoked synaptic plasticity.