Protocol to visualize the distribution of exogenously administered small molecules in the mouse brain

Abstract

Here, we present fixation-driven chemical crosslinking of exogenous ligands, a protocol to visualize the distribution of exogenously administered small molecules in the mouse brain. We first describe the probe design of the small molecules of interest and the probe microinjection into a live mouse brain in detail. We then detail procedures for paraformaldehyde-perfusion fixation. This approach is especially useful for imaging-based evaluation of the small-molecule ligands distribution in mouse brain tissue relying on their interaction with endogenous proteins.