AzoCholine Enables Optical Control of Alpha 7 Nicotinic Acetylcholine Receptors in Neural Networks

Nicotinic
acetylcholine receptors (nAChRs) are essential for cellular
communication in higher organisms. Even though a vast pharmacological
toolset to study cholinergic systems has been developed, control of
endogenous neuronal nAChRs with high spatiotemporal precision has
been lacking. To address this issue, we have generated photoswitchable
nAChR agonists and re-evaluated the known photochromic ligand, BisQ.
Using electrophysiology, we found that one of our new compounds, AzoCholine,
is an excellent photoswitchable agonist for neuronal α7 nAChRs,
whereas BisQ was confirmed to be an agonist for the muscle-type nAChR.
AzoCholine could be used to modulate cholinergic activity in a brain
slice and in dorsal root ganglion neurons. In addition, we demonstrate
light-dependent perturbation of behavior in the nematode, Caenorhabditis elegans.