Pathway-Specific Chemogenetic Manipulation by Applying Ligand to Axonally Expressed DREADDs

New tools for controlling neural populations such as opto- and chemogeneticsChemogenetics afford unprecedented precision in pinpointing the neural circuit substrates of behavior. In addition to the ability of these tools to allow bidirectional control of genetically defined and anatomically defined cell populations, they also offer special advantages for interrogating the behavioral functions of neural pathways, setting them apart from more traditional approaches. In this chapter, we outline considerations for planning chemogeneticChemogenetics pathway-manipulation experiments and describe our protocol for using virally expressed designer receptors exclusively activated by designer drugs (DREADDs) and axonal application of clozapine-n-oxide (CNO)Clozapine-N-oxide (CNO) to modulate neural pathways in behaving rats.