Optical probing of acetylcholine receptors on neurons in the medial habenula with a novel caged nicotine drug analogue

Abstract

Photochemical release of neurotransmitters has been instrumental in the study of their underlying receptors, with acetylcholine being the exception due to its inaccessibility to photochemical protection. We caged a nicotinic acetylcholine receptor (nAChR) agonist, ABT594, via its secondary amine functionality. Effective photolysis could be carried out using either one- or two-photon excitation. Brief flashes (0.5-3.0 ms) of 410 nm light evoked large currents and Ca²⁺ transients on cell bodies and dendrites of medial habenula (MHb) neurons. Unexpectedly, photorelease of ABT594 also revealed nAChR-mediated Ca²⁺ signals along the axons of MHb neurons.