Takahashi Hironori, Kamiya Mako, Kawatani Minoru, Umezawa Keitaro, Ukita Yoshiaki, Niwa Shinsuke, Oda Toshiyuki, Urano Yasuteru
Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, 113-0033 Tokyo, Japan.
Department of Anatomy and Structural Biology, Graduate School of Medicine, University of Yamanashi, Chuo, 409-3898 Yamanashi, Japan.
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6). doi: 10.1073/pnas.2009634118.
is used as a model system to understand the neural basis of behavior, but application of caged compounds to manipulate and monitor the neural activity is hampered by the innate photophobic response of the nematode to short-wavelength light or by the low temporal resolution of photocontrol. Here, we develop boron dipyrromethene (BODIPY)-derived caged compounds that release bioactive phenol derivatives upon illumination in the yellow wavelength range. We show that activation of the transient receptor potential vanilloid 1 (TRPV1) cation channel by spatially targeted optical uncaging of the TRPV1 agonist -vanillylnonanamide at 580 nm modulates neural activity. Further, neuronal activation by illumination-induced uncaging enables optical control of the behavior of freely moving without inducing a photophobic response and without crosstalk between uncaging and simultaneous fluorescence monitoring of neural activity.
秀丽隐杆线虫被用作理解行为神经基础的模型系统,但笼形化合物用于操纵和监测神经活动时,受到线虫对短波长光的先天避光反应或光控的低时间分辨率的阻碍。在这里,我们开发了硼二吡咯亚甲基(BODIPY)衍生的笼形化合物,其在黄色波长范围内光照时会释放生物活性酚衍生物。我们表明,通过在580nm处对TRPV1激动剂 -香草基壬酰胺进行空间靶向光解笼来激活瞬时受体电位香草酸受体1(TRPV1)阳离子通道,可调节神经活动。此外,光照诱导的解笼引起的神经元激活能够对自由移动的线虫行为进行光控,而不会诱导避光反应,也不会在解笼和神经活动的同步荧光监测之间产生串扰。