In Vivo Photopharmacology Enabled by Multifunctional Fibers.
James Allen FrankMarc-Joseph AntoniniPo-Han ChiangAndres CanalesDavid B KonradIndie C GarwoodGabriela RajicFlorian KoehlerYoel FinkPolina AnikeevaPublished in: ACS chemical neuroscience (2020)
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.
Keyphrases
- spinal cord
- neuropathic pain
- drug delivery
- high resolution
- cancer therapy
- high speed
- high throughput
- genome wide
- current status
- white matter
- circulating tumor cells
- high fat diet induced
- type diabetes
- binding protein
- gene expression
- dna methylation
- case control
- adipose tissue
- skeletal muscle
- cerebral ischemia
- subarachnoid hemorrhage