Nonlinear decoding and asymmetric representation of neuronal input information by CaMKIIα and calcineurin

Cell Rep. 2013 Apr 25;3(4):978-87. doi: 10.1016/j.celrep.2013.03.033. Epub 2013 Apr 18.


How information encoded in glutamate release rates at individual synapses is converted into biochemical activation patterns of postsynaptic enzymes remains unexplored. To address this, we developed a dual fluorescence resonance energy transfer (FRET) imaging platform and recorded CaMKIIα and calcineurin activities in hippocampal neurons while varying glutamate uncaging frequencies. With little spine morphological change, 5 Hz spine glutamate uncaging strongly stimulated calcineurin, but not CaMKIIα. In contrast, 20 Hz spine glutamate uncaging, which induced spine growth, activated both CaMKIIα and calcineurin with distinct spatiotemporal kinetics. Higher temporal resolution recording in the soma revealed that CaMKIIα activity summed supralinearly and sensed both higher frequency and input number, thus acting as an input frequency/number decoder. In contrast, calcineurin activity summated sublinearly with increasing input number and showed little frequency dependence, thus functioning as an input number counter. These results provide evidence that CaMKIIα and calcineurin are fine-tuned to unique bandwidths and compute input variables in an asymmetric manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcineurin / metabolism*
  • Calcineurin Inhibitors
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cells, Cultured
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism
  • Fluorescence Resonance Energy Transfer
  • Glutamic Acid / pharmacology
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Rats
  • Tacrolimus / pharmacology


  • Calcineurin Inhibitors
  • Glutamic Acid
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcineurin
  • Calcium
  • Tacrolimus