0046 Chemogenetic activation of A2AR neurons in Nucleus Accumbens increases sleep, affecting cognition and behavior in mice

Abstract Introduction Sleep influences various cognitive and physiologic processes; however, the mechanisms through which sleep affects these different functions are not fully understood. The Nucleus Accumbens (NAc) was recently identified as a regulating center. We hypothesized that manipulation of via chemogenetic activation active Adenosine-2A receptor (A2aR) neurons in NAc core could induce restorative affect memory, anxiety depression-like states mice. Methods transfected A2A A2AR-Cre transgenic mice with an adeno-associated virus (AAV) carrying gene sequence for hM3Dq. Using Clozapine-N-Oxide (CNO) at varying concentrations (0.1, 0.3, 0.9, 2.7 mg/kg), we activated analyzed EEG/EMG traces rapid eye movement (REM) sleep, non-REM (NREM) wakefulness. Mice were then divided into three separate conditions: normal deprivation or increased 4 hr. Following this intervention underwent following behavioral tests 1) Novel object recognition (NOR) test 2) open field (OFT) 3) forced swim (FST) states. Results During first hours A2AR neurons, observed 105% increase NREM highest dose CNO when compared to saline ­treatment. REM similarly. Analysis revealed condition tended perform better NOR test, suggesting memory performance. In OFT, deprived showed significant %time spent center zone total distance travelled within arena. They also significantly less time immobile. exhibited trend towards spending more swimming FST, indicating lower levels Conclusion Our results suggest strongly increases confirming importance sleep/wake regulation. Moreover, improves performance but does Instead, reduced decreases tends reduce depressive-like Support (if any)