Deconstructing behavioral neuropharmacology with cellular specificity

A tailored look at behavioral pharmacology It is important to understand how animal behavior is mediated by molecular, cellular, and circuit components of the brain. However, it has been difficult to link the activity of specific molecules in defined cells to behavioral roles. Shields et al. developed an approach to deconstruct behavioral neuropharmacology with cellular specificity. The technique, termed DART (drugs acutely restricted by tethering), uses enzymatic capture to restrict standard drugs to the surface of genetically specified cells without prior modification of the native pharmacological target. The method provides cell-type specificity, endogenous-protein specificity, acute onset, and utility in behaving animals. This enables the activity of specific molecules in defined circuit elements to be causally linked to behavior. Science , this issue p. eaaj2161