Imaging synaptic inhibition in transgenic mice expressing the chloride indicator, Clomeleon

Brain Cell Biol. 2006 Dec;35(4-6):207-28. doi: 10.1007/s11068-008-9019-6. Epub 2008 Apr 5.


We describe here a molecular genetic approach for imaging synaptic inhibition. The thy-1 promoter was used to express high levels of Clomeleon, a ratiometric fluorescent indicator for chloride ions, in discrete populations of neurons in the brains of transgenic mice. Clomeleon was functional after chronic expression and provided non-invasive readouts of intracellular chloride concentration ([Cl(-)](i)) in brain slices, allowing us to quantify age-dependent declines in resting [Cl(-)](i) during neuronal development. Activation of hippocampal interneurons caused [Cl(-)](i) to rise transiently in individual postsynaptic pyramidal neurons. [Cl(-)](i) increased in direct proportion to the amount of inhibitory transmission, with peak changes as large as 4 mM. Integrating responses over populations of pyramidal neurons allowed sensitive detection of synaptic inhibition. Thus, Clomeleon imaging permits non-invasive, spatiotemporally resolved recordings of [Cl(-)](i) in a large variety of neurons, opening up new opportunities for imaging synaptic inhibition and other forms of chloride signaling.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / ultrastructure
  • Chlorides / analysis*
  • Chlorides / metabolism
  • Electric Stimulation
  • Indicators and Reagents
  • Interneurons / metabolism
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Neural Inhibition / physiology*
  • Neural Pathways / metabolism
  • Neurochemistry / methods*
  • Neurophysiology / methods*
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Pyramidal Cells / metabolism
  • Recombinant Fusion Proteins / genetics*
  • Recombinant Fusion Proteins / metabolism
  • Staining and Labeling / methods*
  • Synapses / metabolism
  • Synaptic Transmission / physiology


  • Chlorides
  • Indicators and Reagents
  • Recombinant Fusion Proteins
  • clomeleon