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

我们之前开发了第一个腺苷A2A受体（A2AR）的阳性变构调节剂，命名为A2AR PAM-1，与经典的A2AR激动剂不同，它能唤起大脑中的A2AR反应（例如，睡眠诱导），而不影响心血管功能。我们现在正在与Abe实验室（广岛大学高级科学与工程研究生院）合作开发一种可见光（420纳米）光激活（“笼状”）A2AR PAM-1。利用光学版本的A2AR PAM，我们首次在行为自由的小鼠中光化学诱导睡眠，并证明伏隔核的胶质细胞和神经元产生的细胞外腺苷促进睡眠[Roy K et al., in preparation]。

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].