Diurnal Variations in the Cholinergic System of the Nucleus Accumbens

The nucleus accumbens (NAc) plays a critical role in reward-related behaviors, which exhibit diurnal variations. Cholinergic interneurons (CINs) are the primary source of acetylcholine within the NAc and regulate local dopamine (DA) signaling through nicotinic acetylcholine receptors (nAChRs). Although there are diurnal variations in NAc dynamics, little is known about whether CIN activity and nicotinic signaling also vary across the light/dark cycle. Here, we aimed to determine diurnal variations in the NAc cholinergic system using ex vivo fast-scan cyclic voltammetry and cell-attached electrophysiological recordings in male rodents. We examined time-of-day-dependent differences in nAChR-mediated modulation of DA release, spontaneous CIN firing frequency, and firing patterns. We found that spontaneous CIN firing varied across the light/dark cycle, with increased activity during the dark cycle. Additionally, bath application of nicotine (NIC), mecamylamine (MEC), and dihydro-{beta}-erythroidine (DH{beta}E) reduced CIN firing frequency during the dark cycle, with only MEC decreasing firing frequency in the light cycle. NIC and MEC also altered CIN firing patterns during the dark cycle, whereas DH{beta}E primarily affected firing frequency. Together, these findings demonstrate diurnal variations in NAc CIN activity and reveal time-of-day-dependent differences in the effects of nAChR modulation on spontaneous firing. These results suggest that nicotinic signaling may contribute to diurnal regulation of NAc cholinergic activity, providing insight into mechanisms underlying time-of-day-dependent changes in reward circuitry.