Translational PET applications for brain circuit mapping with transgenic neuromodulation tools

Abstract

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. 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 utilized to transduce specific cells to express transgenic receptors and opsins capable of manipulating neuronal activity. These allow mapping of neuroanatomical projection sites and link cellular manipulations with brain circuit functions and behavior. As these tools continue to expand knowledge of the nervous system in preclinical models, developing translational applications for human therapies is becoming increasingly possible. However, new strategies for implementing and monitoring transgenic tools are needed for safe and effective use in translational research and potential clinical applications. A major challenge for such applications is the need to 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 for in vivo mapping and manipulation of brain circuits and to propose future directions for translational applications.