Sleep modulation via Nucleus Accumbens A2AR neurons to probe cognition and behavior in mice

A key tool to investigate the putative function(s) of sleep is a model system in which sleep can be manipulated to design gain-of-function experiments and loss-of-function experiments i.e. increasing and decreasing sleep amounts to assess the effects on outcome variables. Here we utilize adenosine 2A receptor expressing neurons in the Nucleus Accumbens core (NAcc^A2AR neurons) to perform gain-of-function experiments by controlling natural sleep circuits in mice to assess the effects of varying amounts of sleep on cognition and mood. Specifically, we either enhanced NREM sleep and REM sleep by chemogenetic activation of NAcc^A2AR neurons in our mice, allowed them to sleep normally, or sleep deprived them before running them through the novel object recognition test, open field test, and the forced swim test to assess memory performance as well as levels of anxiety- and depression-like behaviors. Our results suggest a linear relationship between amounts of sleep and levels of anxiety-related behaviors, in that more sleep is positively correlated with higher levels of anxiety.