Translational PET imaging applications for brain circuit mapping and manipulation with transgenic tools.

Transgenic neuromodulation tools have transformed the field of neuroscience over the past two decades by enabling targeted manipulation of neuronal populations and circuits with unprecedented specificity. Of these technologies, chemogenetic and optogenetic neuromodulation systems are among the most widely used and allow targeted control of neuronal activity through the administration of a selective compound or light, respectively. Innovative genetic targeting strategies are used to transduce specific cells to express transgenic receptors and opsins. These allow for mapping neuroanatomical projection sites and link cellular manipulations with brain activity and behavior. As these tools continue to expand knowledge of the nervous system in preclinical models, the potential to develop translational applications for human therapies is becoming increasingly feasible. However, new strategies for implementing and monitoring transgenic tools are needed for safe and practical use in both translational applications and in humans. A major challenge for such applications is the need to noninvasively track the location and function of chemogenetic receptors and opsins in vivo, and new developments in positron emission tomography (PET) imaging techniques offer promising solutions. The goal of this review is to summarize current research combining transgenic tools with PET imaging for in vivo mapping and manipulation of brain circuits and to propose future directions for translational applications. This work was funded in part by the National Institute on Drug Abuse Intramural Research Program.