A chemogenetic technology, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) affords a means to temporally and remotely control the activity of a target neural population expressing a "designer receptor" by an agonist compound. The combination muscarinic-based DREADDs, hM3Dq (excitatory) and hM4Di (inhibitory), and biologically inert compound, clozapine-N-oxide (CNO) has been successfully applied in a variety of in vitro and in vivo contexts, extending to non-human primate studies to modify behavior. For the application of DREADDs to non-human primates, it is desirable to monitor the DREADD expression in vivo because in non-human primates, 1) viral vector-based transgene delivery into target neurons has not been fully established, and 2) the behavioral study is performed for relatively the long-term. In addition, CNO has poor brain permeability and can be metabolized to clozapine, which has potential for causing unwanted off-target actions. We solved these issues by developing a novel ligand, deschloroclozapine (DCZ), which serves a dual purpose in chemogenetics: (1) as a selective compound for visualization of DREADD expression in vivo by positron emission tomography (PET) imaging and (2) as a selective agonist for muscarinic-based DREADDs. In this talk, I will introduce the property of DCZ and the role of PET imaging in neuroscience research using non-human primates.

To: abstract pdf