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

Abstract

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 freely moving C. elegans without inducing a photophobic response and without crosstalk between uncaging and simultaneous fluorescence monitoring of neural activity.

BODIPY-based photocages: rational design and their biomedical application

“…Then, the same research group went on to develop photocages 25a–d based on a π-extended furo[ b ]-fused BODIPY derivative, which could be uncaged by illumination at 580 nm (Scheme 22b). 56 Although the uncaging quantum yields of 25a–d were relatively low ( Φ u = 1.3–4.9 × 10 −4 ), the high molar absorption coefficient of the furo[ b ]-fused BODIPY fluorophore resulted in a good overall efficiency of species release. Since uncaging was most efficient when the HOMO energy level of the aryl group was around −0.21 Hartree, N -vanillylnonanamide (VN) with a HOMO energy level of −0.21 Hartree, was chosen to be incorporated at the boron of the BODIPY core to construct photocage 25e .…”

Spatiotemporal Control of Biology: Synthetic Photochemistry Toolbox with Far-Red and Near-Infrared Light

“…40 While this approach has not yet been expanded to the far-red/NIR, recent improvements have yielded a BODIPY photocage that is cleaved with yellow light and elegantly used to control neural activity in C. elegans. 41 In an alternative approach to photocages based on BODIPY fluorophores, Winter and Weinstain independently reported meso-methyl BODIPY as photocages that can be cleaved with green light (Figure 2a). 42,43 The meso-methyl BODIPY photocages were successfully tuned to improve the quantum yield of the photoreaction to up to 95% (Φ rel ≤ 0.95).…”

“…In this work, phenol or coumarin groups were attached to the boron and were shown to be effective leaving groups upon excitation with green (500 nm) light . While this approach has not yet been expanded to the far-red/NIR, recent improvements have yielded a BODIPY photocage that is cleaved with yellow light and elegantly used to control neural activity in C. elegans …”