Photoswitchable ligands can add an optical switch to a target receptor or signaling cascade and enable reversible control of neural circuits. The application of this approach, termed photopharmacology, to behavioral experiments has been impeded by a lack of integrated hardware capable of delivering both light and compounds to deep brain regions in moving subjects. Here, we devise a hybrid photochemical genetic approach to target neurons using a photoswitchable agonist of the capsaicin receptor TRPV1, red-AzCA-4. Using multifunctional fibers with optical and microfluidic capabilities, we delivered a transgene coding for TRPV1 into the ventral tegmental area (VTA). This sensitized excitatory VTA neurons to red-AzCA-4, allowing us to optically control conditioned place preference in mice, thus extending applications of photopharmacology to behavioral experiments. Applied to endogenous receptors, our approach may accelerate future studies of molecular mechanisms underlying animal behavior.

中文翻译：

---

多功能纤维实现的体内光药理学

光开关配体可以将光开关添加到目标受体或信号级联，并实现神经回路的可逆控制。这种称为光药理学的方法在行为实验中的应用受到阻碍，原因是缺乏能够将光和化合物输送到移动受试者大脑深部区域的集成硬件。在这里，我们设计了一种混合光化学遗传方法，使用辣椒素受体 TRPV1红色-AzCA-4 的光开关激动剂来靶向神经元。使用具有光学和微流体功能的多功能纤维，我们将 TRPV1 的转基因编码传递到腹侧被盖区 (VTA)。这使兴奋性 VTA 神经元对红色敏感-AzCA-4，使我们能够光学控制小鼠的条件性位置偏好，从而将光药理学的应用扩展到行为实验。应用于内源性受体，我们的方法可能会加速未来对动物行为背后的分子机制的研究。