2022
DOI: 10.3389/fncel.2022.844243
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A Subset of Nucleus Accumbens Neurons Receiving Dense and Functional Prelimbic Cortical Input Are Required for Cocaine Seeking

Abstract: BackgroundPrelimbic cortical projections to the nucleus accumbens core are critical for cue-induced cocaine seeking, but the identity of the accumbens neuron(s) targeted by this projection, and the transient neuroadaptations contributing to relapse within these cells, remain unknown.MethodsMale Sprague-Dawley rats underwent cocaine or sucrose self-administration, extinction, and cue-induced reinstatement. Pathway-specific chemogenetics, patch-clamp electrophysiology, in vivo electrochemistry, and high-resoluti… Show more

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Cited by 17 publications
(23 citation statements)
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“…Optogenetic activation of NAc D2-MSNs that project to the dlVP attenuates contextual cocaine seeking 9,26,83 , so NPAS4-dependent suppression of mPFCàNAc D2-MSN circuit strengthening is clearly important for place conditioning and drug-cue associations that promote cocaine seeking. Clearly, there are multiple glutamatergic inputs to the NAc that are important for regulating addiction-related behaviors in rodents 13,73 , but the PrLàNAcore plays an essential role in cue-reinstated drug seeking 10,12 , and we showed here that the activity of this same circuit is required for development of cocaine CPP. Compared to NAc D1-MSNs, NAc D2-MSNs receive a stronger excitatory input from the mPFC 72 , suggesting the important need for NPAS4 to suppress drug-induced strengthening of glutamatergic inputs onto D2-MSNs.…”
Section: Discussionmentioning
confidence: 56%
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“…Optogenetic activation of NAc D2-MSNs that project to the dlVP attenuates contextual cocaine seeking 9,26,83 , so NPAS4-dependent suppression of mPFCàNAc D2-MSN circuit strengthening is clearly important for place conditioning and drug-cue associations that promote cocaine seeking. Clearly, there are multiple glutamatergic inputs to the NAc that are important for regulating addiction-related behaviors in rodents 13,73 , but the PrLàNAcore plays an essential role in cue-reinstated drug seeking 10,12 , and we showed here that the activity of this same circuit is required for development of cocaine CPP. Compared to NAc D1-MSNs, NAc D2-MSNs receive a stronger excitatory input from the mPFC 72 , suggesting the important need for NPAS4 to suppress drug-induced strengthening of glutamatergic inputs onto D2-MSNs.…”
Section: Discussionmentioning
confidence: 56%
“…One of the strongest glutamatergic inputs onto NAc D2-MSNs comes from the mPFC 72,74 , and prelimbic (PrL) mPFC pyramidal neuron projections to the NAcore are required for cue-reinstated cocaine seeking in rats 1,8,10,12,[75][76][77] . To test the importance of the PrLàNAc circuit for mouse cocaine CPP, we infused in NAc a retrograde virus expressing Cre-recombinase (rgAAV-Cre) and a Cre-dependent Gi-DREADD in the mPFC (AAV2-hM4Di-mCherry) to allow for CNO-dependent suppression of PrLàNAc projection neuron activity during cocaine conditioning (Figure 6D; Figure S7B).…”
Section: Npas4 Blocks Cocaine Conditioning-induced Dendritic Spine Gr...mentioning
confidence: 99%
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“…In keeping with these findings, our laboratory and others have demonstrated drug- and withdrawal-dependent reductions in the morphometric features of astrocytes and reduced synaptic interaction within the nucleus accumbens, phenomenon that has been directly linked to relapse vulnerability following drug exposure and withdrawal. Additionally, re-exposure to drug-conditioned cues also induces astrocytic structural plasticity and restores astrocytic synaptic presence in the nucleus accumbens, with these astrocytic changes critical in limiting cue-drug seeking [30] , [31] , [43] , [33] , [71] . Changes in astroglial structure and synaptic interaction are often accompanied by additional functional adaptations including downregulation of GFAP and the glutamate transporter, GLT-1, resulting in impaired glutamate homeostasis at the tripartite synapse [30] , [72] .…”
Section: Introductionmentioning
confidence: 99%
“…The unique serotype-specific properties of adenoviral vectors enable transduction of neurons by virtue of their projection targets or their inputs. As an example, AAV1-mediated anterograde transsynaptic activity can be used to interrogate input-specific populations of neurons [71] , [142] , [143] , [144] , [145] . Recently, the Kuhn laboratory established AAV1-mediated anterograde vectors also allow for the axo-astrocytic delivery of Cre at the tripartite synapse [146] , making it possible to genetically tag astrocytes at anatomically-defined synapses and evaluate if these astrocytes uniquely respond to and modulate circuit activity.…”
Section: Introductionmentioning
confidence: 99%