title: Nonlinear decoding and asymmetric representation of neuronal input information by CaMKIIα and calcineurin.
abstract: 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.
authors.affiliation: Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujii
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inoue
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okuno
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sano
authors.forename: Sayaka
authors.initials: S
authors.lastname: Takemoto-Kimura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitamura
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Bito
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D065095:Calcineurin Inhibitors; D018698:Glutamic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019703:Calcineurin; D002118:Calcium; D016559:Tacrolimus