4.8 Article

Neural and behavioral control in Caenorhabditis elegans by a yellow-light-activatable caged compound

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2009634118

Keywords

caged compounds; C. elegans; photocontrol; fluorescence imaging; photolysis

Funding

  1. Japan Agency for Medical Research and Development (AMED) [JP19gm0710008]
  2. Japan Science and Technology Agency (JST)/Precursory Research for Embryonic Science and Technology (PRESTO) [JPMJPR14F8]
  3. Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promotion of Science (JSPS) KAKENHI [JP16H02606, JP26111012, JP19H05632, JP17H05057, JP16H06536]
  4. JSPS Coreto-Core Program, A. Advanced Research Networks [JPJSCCA20170007, JP15H05951, JP20H05724, JP15J05894, JP19K16291]
  5. Takeda Science Foundation
  6. Naito Foundation
  7. Uehara Memorial Foundation
  8. Senri Life Science Foundation
  9. Daiichi Sankyo Foundation of Life Science
  10. Association for Fordays Self-Reliance Support in Japan
  11. Konica Minolta Science and Technology Foundation

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By developing BODIPY-derived caged compounds that release bioactive phenol derivatives upon illumination in the yellow wavelength range, optical control of neural activity in Caenorhabditis elegans can be achieved without inducing a photophobic response or crosstalk between uncaging and simultaneous fluorescence monitoring.
Caenorhabditis elegans 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 N-vanillylnonanamide at 580 nm modulates neural activity. Further, neuronal activation by illumination-induced uncaging enables optical control of the behavior of freelymoving C. elegans without inducing a photophobic response and without crosstalk between uncaging and simultaneous fluorescence monitoring of neural activity.

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