Abstract
The nucleus accumbens (NAc) is located in the ventromedial portion of the striatum and is vital to valence-based predictions and motivated action. The neural architecture of the NAc allows for complex interactions between various cell types that filter incoming and outgoing information. Dopamine (DA) input serves a crucial role in modulating NAc function, but the mechanisms that control terminal DA release and its effect on NAc neurons continues to be elucidated. The endocannabinoid (eCB) system has emerged as an important filter of neural circuitry within the NAc that locally shapes terminal DA release through various cell type- and site-specific actions. Here, we will discuss how eCB signaling modulates terminal DA release by shaping the activity patterns of NAc neurons and their afferent inputs. We then discuss recent technological advancements that are capable of dissecting how distinct cell types, their afferent projections, and local neuromodulators influence valence-based actions.
Highlights
Accurate valence-based predictions and appropriate action sequences are necessary for survival, and disruptions in this process underlie numerous neuropsychiatric disorders
Witten et al (2010) found optogenetic excitation of nucleus accumbens (NAc) cholinergic interneurons (CINs) inhibited medium spiny neurons (MSNs) firing via nAChR-dependent activation of GABA release, the source of GABAergic input is unclear
2-Arachidonoylglycerol is more abundant than AEA in most brain regions, is a full agonist for the cannabinoid type 1 (CB1) receptor, and is the primary eCB involved in CB1-mediated inhibition of presynaptic neurotransmitter release (Ohno-Shosaku and Kano, 2014)
Summary
Accurate valence-based predictions and appropriate action sequences are necessary for survival, and disruptions in this process underlie numerous neuropsychiatric disorders. Seminal work aimed at understanding the function and dysfunction of the NAc has identified separate cell populations based on molecular profile, electrophysiological properties, or output target that differentially influence valence-based behaviors (Gerfen and Surmeier, 2011; Lobo and Nestler, 2011). This classification system of striatal neurons has massively influenced our understanding of the neurobiology of motivated behavior, disease, and its treatment (Alexander et al, 1986; Albin et al, 1989). We end by discussing recent technological advancements that will facilitate this endeavor (section “Conclusions, Caveats, and Future Directions”)
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