Light-activated serotonin for exploring its action in biological systems

  • Chem Biol. 2013 Dec 19;20(12):1536-46. doi: 10.1016/j.chembiol.2013.11.005.
Adam C Rea  1 Laura N Vandenberg  2 Rebecca E Ball  3 Ashley A Snouffer  4 Alicia G Hudson  3 Yue Zhu  1 Duncan E McLain  5 Lindsey L Johnston  4 James D Lauderdale  3 Michael Levin  2 Timothy M Dore  6
Affiliations
  • 1. Department of Chemistry, University of Georgia, Athens, GA 30602, USA.
  • 2. Biology Department and Tufts Center for Regenerative and Developmental Biology, Tufts University, Suite 4600, 200 Boston Avenue, Medford, MA 02155-4243, USA.
  • 3. Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
  • 4. Department of Genetics, University of Georgia, Athens, GA 30602, USA.
  • 5. Department of Chemistry, University of Georgia, Athens, GA 30602, USA; New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates.
  • 6. Department of Chemistry, University of Georgia, Athens, GA 30602, USA; New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates. Electronic address: [email protected].
Abstract

Serotonin (5-HT) is a neuromodulator involved in regulating mood, appetite, memory, learning, pain, and establishment of left-right (LR) asymmetry in embryonic development. To explore the role of 5-HT in physiology, we have created two forms of "caged" 5-HT, BHQ-O-5HT and BHQ-N-5HT. When exposed to 365 or 740 nm light, BHQ-O-5HT releases 5-HT through one- or two-photon excitation, respectively. BHQ-O-5HT mediated changes in neural activity in cultured mouse primary sensory neurons and the trigeminal ganglion and optic tectum of intact zebrafish larvae in the form of high-amplitude spiking in response to light. In Xenopus laevis embryos, light-activated 5-HT increased the occurrence of LR patterning defects. Maximal rates of LR defects were observed when 5-HT was released at stage 5 compared with stage 8. These experiments show the potential for BHQ-caged serotonins in studying 5-HT-regulated physiological processes.

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