Department of Molecular and Cell Biology , University of California, Berkeley , Berkeley , California 94720 , United States.
J Am Chem Soc. 2018 Jun 20;140(24):7445-7448. doi: 10.1021/jacs.8b03942. Epub 2018 Jun 6.
Photoswitchable neurotransmitter receptors are powerful tools for precise manipulation of neural signaling. However, their applications for slow or long-lasting biological events are constrained by fast thermal relaxation of cis-azobenzene. We address this issue by modifying the ortho positions of azobenzene used in the tethered ligand. In cultured cells and intact brain tissue, conjugating inhibitory neurotransmitter receptors with one of the derivatives, dMPC1, allows bidirectional receptor control with 380 and 500 nm light. Moreover, the receptors can be locked in either an active or an inactive state in darkness after a brief pulse of light. This strategy thus enables both rapid and sustained manipulation of neurotransmission, allowing optogenetic interrogation of neural functions over a broad range of time scales.
光可切换神经递质受体是精确操纵神经信号的有力工具。然而，由于顺式偶氮苯的快速热弛豫，它们在缓慢或持久的生物事件中的应用受到限制。我们通过修饰在连接配体中使用的偶氮苯的邻位来解决这个问题。在培养的细胞和完整的脑组织中，将抑制性神经递质受体与一种衍生物 dMPC1 缀合，可以使用 380nm 和 500nm 光进行双向受体控制。此外，受体在短暂的光脉冲后可以在黑暗中锁定在活跃或不活跃状态。因此，这种策略既可以快速又可以持续地操纵神经传递，从而可以在广泛的时间尺度上进行神经功能的光遗传学研究。
