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

我们先前开发了腺苷A2 A受体（A2 AR）的第一个正变构调节剂，命名为A2 AR PAM-1，其在脑中引起A2 AR反应（例如，睡眠诱导），而不影响心血管功能，不像经典的A2 AR激动剂。我们现在正在与安倍实验室（广岛大学，高等科学与工程研究科）合作开发可见光（420 nm）光活化（“笼”）A2 AR PAM-1。使用A2 AR PAM的光学版本，我们首次在自由行为的小鼠中光化学诱导睡眠，并证明由神经胶质细胞和神经元在丘脑核中产生的细胞外腺苷促进睡眠[Roy K et al.，正在编写中]。

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].