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演題詳細

Oral

神経イメージング
Neuro Imaging

開催日 2014/9/11
時間 10:00 - 11:00
会場 Room H(304)
Chairperson(s) 喜多村 和郎 / Kazuo Kitamura (東京大学大学院医学系研究科 神経生理学 / Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Japan)
今井 猛 / Takeshi Imai (理化学研究所 発生・再生科学総合研究センター(理研CDB) / RIKEN Center for Developmental Biology, Japan)

CaMKIIαとCalcineurinによる神経入力情報の非線形デコーディング
Nonlinear Decoding and Asymmetric Representation of Neuronal Input Information by CaMKIIα and Calcineurin

  • O1-H-2-2
  • 藤井 哉 / Hajime Fujii:1 井上 昌俊 / Masatoshi Inoue:1 奥野 浩行 / Hiroyuki Okuno:2 佐野 慶和 / Yoshikazu Sano:3 竹本-木村 さやか / Sayaka Takemoto-Kimura:1 喜多村 和郎 / Kazuo Kitamura:3 狩野 方伸 / Masanobu Kano:3 尾藤 晴彦 / Haruhiko BIto:1 
  • 1:東京大学大学院医学系研究科神経生化学 / Department of Neurochemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 2:京都大学大学院医学研究科メディカルイノベーションセンター / Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan 3:東京大学大学院医学系研究科神経生理学 / Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 

The nervous system adapts to a fluctuating environment through activity-dependent modulation of neuronal properties. CaMKII and calcineurin have been suggested to play key roles in decoding of neural input parameters and synaptic plasticity. However, several important theoretical postulates underlying the role of these enzymes during synaptic plasticity-e.g. that CaMKII in spines functions as a high-frequency input detector or that calcineurin is uniquely activated by low-frequency stimulation remain untested in living synapses. In particular, evidence is lacking whether distinct sets of incoming glutamate stimulation parameters can be transformed into a differential spatio-temporal activation patterns of the Ca2+-sensitive biochemical effectors.
To address these issues, we developed dFOMA (dual FRET with optical manipulation) imaging that permitted simultaneous measurement of CaMKIIα and calcineurin activities in spines of hippocampal neurons, while varying glutamate uncaging stimulation frequencies. 5 Hz spine glutamate uncaging strongly stimulated calcineurin but not CaMKIIα, with little spine morphological change. In contrast, 20 Hz spine glutamate uncaging which induced spine morphological plasticity activated both CaMKIIα and calcineurin, with distinct spatial activation patterns. Treatment with a calcineurin inhibitor FK-506 did not significantly change the CaMKIIα responses triggered by either 20 Hz or 5 Hz glutamate uncaging, although it modestly increased baseline CaMKIIα activity. Higher temporal resolution recording in the soma revealed that CaMKIIα sensed both higher frequency and input number, whereas calcineurin 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.

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