Understanding the mechanism of sleepiness by exploring mesolimbic glia-neuron interactions

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We previously developed the first positive allosteric modulator of adenosine A2A receptors (A2AR), named A2AR PAM-1, that evokes A2AR responses in the brain (e.g., sleep induction) without affecting cardiovascular function, unlike classic A2AR agonists. We are now collaborating with the Abe Lab (Hiroshima University, Graduate School of Advanced Science and Engineering) to develop a visible-light (420 nm) photoactivatable (‘caged’) A2AR PAM-1. Using the opto-version of the A2AR PAM, we, for the first time, optochemically induced sleep in freely behaving mice and demonstrated that extracellular adenosine produced by glia and neurons in nucleus accumbens promotes sleep [Roy K et al., in preparation].