Photocontrol of zebrafish behavior with a photoswitchable antagonist of α7 nicotinic acetylcholine receptors

The α7 nicotinic acetylcholine receptor (α7 nAChR) is a key modulator of cognitive function, inflammation, and neuronal signaling, making it an attractive therapeutic target for neurodegenerative and neuropsychiatric disorders. However, traditional pharmacological interventions lack precise spatial and temporal control, often leading to off-target effects. Photopharmacology offers a novel approach to modulate α7 nAChRs with high precision. Here, we present the functional characterization of a novel photoswitchable α7 ligand, CPZ-2. Behavioral assays in zebrafish larvae revealed the ability of CPZ-2 to modulate nicotine-induced locomotion in a light-dependent manner. Our findings establish CPZ-2 as a promising tool for optically controlled α7 nAChR modulation, with potential applications in neuroscience, inflammation, and pain research. Further studies will explore its utility in circuit dissection and therapeutic interventions.