Covalent anchoring of tethered ligands to chemogenetic handles for targeted in vivo neuropharmacology

Covalent anchoring of tethered ligands to chemogenetic handles (CATCH) is a chemogenetic approach that enables sustained, localized, and pharmacologically specific receptor antagonism. Here, we present a protocol for designing and applying CATCH in mice. We describe how to integrate CATCH with ex vivo and in vivo electrophysiological recordings, as well as detail procedures for combining CATCH with behavioral assays. CATCH enables the specific control of neurotransmitter receptor function, offering a tool for both neurophysiology and behavioral studies. For complete details on the use and execution of this protocol, please refer to Jehl et al.¹.