Abstract
Photoswitchable ligands can add an optical switch to a target receptor or signaling cascade and enable reversible control of neural circuits. The application of this approach, termed photopharmacology, to behavioral experiments has been impeded by a lack of integrated hardware capable of delivering both light and compounds to deep brain regions in moving subjects. Here, we devise a hybrid photochemical genetic approach to target neurons using a photoswitchable agonist of the capsaicin receptor TRPV1, red-AzCA-4. Using multifunctional fibers with optical and microfluidic capabilities, we delivered a transgene coding for TRPV1 into the ventral tegmental area (VTA). This sensitized excitatory VTA neurons to red-AzCA-4, allowing us to optically control conditioned place preference in mice, thus extending applications of photopharmacology to behavioral experiments. Applied to endogenous receptors, our approach may accelerate future studies of molecular mechanisms underlying animal behavior.
Polina Anikeeva
Matoula S. Salapatas Professor and Head, Department of Materials Science and EngineeringProfessor, Brain and Cognitive SciencesDirector, K. Lisa Yang Brain-Body CenterAssociate Investigator, McGovern Institute for Brain ResearchAssociate Director, Research Laboratory of Electronics
My goal is to combine the current knowledge of biology and nanoelectronics to develop materials and devices for minimally invasive treatments for neurological and neuromuscular diseases.