Abstract
Dopamine action in the nucleus accumbens (NAc) is thought to drive appetitive behavior and Pavlovian reward learning. However, it remains controversial how dopamine achieves these behavioral effects by regulating medium spiny projection neurons (MSNs) of the NAc, especially on a behaviorally relevant timescale. Metabotropic glutamate receptor (mGluR)-induced Ca(2+) signaling dependent on the Ca(2+)- releasing messenger inositol 1,4,5-triphosphate (IP3) plays a critical role in controlling neuronal excitability and synaptic plasticity. Here, we show that transient dopamine application facilitates mGluR/IP3-induced Ca(2+) signals within a time window of ∼2-10 s in a subpopulation of MSNs in the NAc core. Dopamine facilitation of IP3-induced Ca(2+) signaling is mediated by D1 dopamine receptors. In dopamine-insensitive MSNs, activation of A2A adenosine receptors causes enhancement of IP3-evoked Ca(2+) signals, which is reversed by D2 dopamine receptor activation. These results show that dopamine differentially regulates Ca(2+) signaling on the order of seconds in two distinct MSN subpopulations.
Highlights
The nucleus accumbens (NAc), which constitutes a major part of the ventral striatum, plays a critical role in driving appetitive behavior, Pavlovian reward learning, and the development of addiction (Day and Carelli, 2007; Fields et al, 2007; Ikemoto and Bonci, 2014)
In this study, using ex vivo slices from mice, we investigated how DA differentially regulates Metabotropic glutamate receptor (mGluR)/IP3-dependent Ca2+ signaling via D1 and D2 receptors in the NAc core, the subregion predominantly involved in the formation and expression of cue-reward memory (Saddoris et al, 2013; Sesack and Grace, 2010)
Phasic DA Enhances IP3-Induced Ca2+ Signals in a Timing-Dependent Manner in a Subset of medium spiny neurons (MSNs) Whole-cell voltage-clamp recordings of MSNs were made in the NAc core
Summary
The nucleus accumbens (NAc), which constitutes a major part of the ventral striatum, plays a critical role in driving appetitive behavior, Pavlovian reward learning, and the development of addiction (Day and Carelli, 2007; Fields et al, 2007; Ikemoto and Bonci, 2014). Dopamine (DA) neurons in the VTA and the adjacent substantia nigra display transient increases in firing frequency, or bursts, in response to unexpected primary reward or to reward-predicting environmental cues after repeated cuereward conditioning (Schultz, 1998), eliciting phasic DA transients lasting several seconds in the NAc and other target areas (Day et al, 2007; Phillips et al, 2003). Ample evidence implicates these DA transients in motivating goal-directed behaviors aimed at reward or reward-predicting cues and in the learning of cues and behaviors leading to reward. It has been shown that AP-evoked Ca2+ signals can be amplified by preceding activation of group I metabotropic glutamate receptors (mGluRs) coupled to the generation of inositol-1,4,5-triphosphate (IP3) in DA neurons, hippocampal pyramidal neurons, and cerebellar
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
