In Vivo Photopharmacology Enabled by Multifunctional Fibers

ACS Chem Neurosci. 2020 Nov 18;11(22):3802-3813. doi: 10.1021/acschemneuro.0c00577. Epub 2020 Oct 27.


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.

Keywords: Photopharmacology; TRPV1; capsaicin; chemical genetics; fibers; neural probes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal
  • Conditioning, Classical
  • Ligands
  • Mice
  • Neurons*
  • Ventral Tegmental Area*


  • Ligands