Cloaked Caged Compounds: Chemical Probes for Two-Photon Optoneurobiology

Angew Chem Int Ed Engl. 2017 Jan 2;56(1):193-197. doi: 10.1002/anie.201609269. Epub 2016 Dec 2.

Abstract

Caged neurotransmitters, in combination with focused light beams, enable precise interrogation of neuronal function, even at the level of single synapses. However, most caged transmitters are, surprisingly, severe antagonists of ionotropic gamma-aminobutyric acid (GABA) receptors. By conjugation of a large, neutral dendrimer to a caged GABA probe we introduce a "cloaking" technology that effectively reduces such antagonism to very low levels. Such cloaked caged compounds will enable the study of the signaling of the inhibitory neurotransmitter GABA in its natural state using two-photon uncaging microscopy for the first time.

Keywords: GABA-A receptors; biologically inert; caged compounds; optical methods; two-photon photolysis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendrimers / chemistry*
  • Dendrimers / metabolism
  • Dendrimers / pharmacology
  • Female
  • GABA-A Receptor Antagonists / chemistry*
  • GABA-A Receptor Antagonists / metabolism
  • GABA-A Receptor Antagonists / pharmacology
  • Male
  • Mice
  • Microscopy, Fluorescence / methods
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Optical Imaging / methods*
  • Photolysis
  • Photons
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Dendrimers
  • GABA-A Receptor Antagonists
  • gamma-Aminobutyric Acid