In vivo photopharmacology enabled by multifunctional fibers

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.

Publication
ACS Chem. Neurosci.
James A Frank
Assistant Professor at Vollum Institute, OHSU
Marc-Joseph Antonini
Marc-Joseph Antonini
Postdoctoral Associate

Working towards enhancing human health and capabilities by combining engineering and neurosciences.

Pohan Chiang
Assistant Professor at National Chiao Tung University
Andres Canales
Researcher at Advanced Silicon Group
Indie Garwood
Indie Garwood
Graduate Student

Graduate student developing neurotechnology to study anesthesia | Devoted dog + cat mom

Florian Koehler
Florian Koehler
Graduate Student

Neuroengineer

Polina Anikeeva
Polina Anikeeva
Professor in Materials Science and Engineering
Professor in Brain and Cognitive Sciences
Associate 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.

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