Photocontrol of Endogenous Glycine Receptors In Vivo

Highlights

• The photochromic small molecule Glyght enables control of glycine receptors with light

• Glyght is active and selective in endogenous human and zebrafish receptors

• Glyght is reversible in endogenous human and zebrafish receptors in vitro and in vivo

• Glyght constitutes a new molecular scaffold for glycine receptor pharmacology

Summary

Glycine receptors (GlyRs) are indispensable for maintaining excitatory/inhibitory balance in neuronal circuits that control reflexes and rhythmic motor behaviors. Here we have developed Glyght, a GlyR ligand controlled with light. It is selective over other Cys-loop receptors, is active in vivo, and displays an allosteric mechanism of action. The photomanipulation of glycinergic neurotransmission opens new avenues to understanding inhibitory circuits in intact animals and to developing drug-based phototherapies.