Differential Dopamine Regulation of Ca super(2+) Signaling and Its Timing Dependence in the Nucleus Accumbens

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 super(2+) signaling dependent on the Ca super(2+)- releasing messenger inositol 1,4,5-triphosphate (IP sub(3)) plays a critical role in controlling neuronal excitability and synaptic plasticity. Here, we show that transient dopamine application facilitates mGluR/IP sub(3)-induced Ca super(2+) signals within a time window of similar to 2-10 s in a subpopulation of MSNs in the NAc core. Dopamine facilitation of IP sub(3)-induced Ca super(2+) signaling is mediated by D1 dopamine receptors. In dopamine-insensitive MSNs, activation of A2A adenosine receptors causes enhancement of IP sub(3)-evoked Ca super(2+) signals, which is reversed by D2 dopamine receptor activation. These results show that dopamine differentially regulates Ca super(2+) signaling on the order of seconds in two distinct MSN subpopulations.