Imaging of calcineurin activated by long-term depression-inducing synaptic inputs in living neurons of rat visual cortex

Hiroki Yasuda, Hideyoshi Higashi, Yoshihisa Kudo, Takafumi Inoue, Yoshio Hata, Katsuhiko Mikoshiba, Tadaharu Tsumoto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Long-term depression (LTD) of synaptic transmission is induced by low-frequency stimulation (LFS) of afferents lasting for a long time, typically for 10-15 min, in neocortical and hippocampal slices. It is suggested that calcineurin, Ca2+/calmodulin-dependent protein phosphatase, plays a role in the induction of LTD, based on the results that pharmacological or genetic manipulation of calcineurin activity interfered in its induction. However, questions as to why it takes so long to induce LTD and in which compartment of neurons calcineurin is activated remain unanswered. With a fluorescent indicator for calcineurin activity, we visualized the spatiotemporal pattern of its activation in living neurons in layer II/III of visual cortical slices of rats during the LFS of layer IV that induced LTD of synaptic responses. During LFS, the fluorescence intensity gradually increased with a latency of a few minutes in dendrites and soma of neurons, and remained increased during the whole observation period (10-25 min) after LFS. The onset latency of the increase in the soma was slower than that in the distal dendritic region. The LFS-induced rise in fluorescence was not observed in neurons which were loaded with inhibitors of calcineurin, indicating that the intensity of fluorescence reflects calcineurin activity. Control stimulation at 0.05 Hz and θ-burst stimulation did not significantly change the intensity of fluorescence. Only LFS-type inputs effectively activate calcineurin in postsynaptic neurons in an augmenting manner, and such a time-consuming activation of calcineurin may be a reason why long-lasting LFS is necessary for the induction of LTD.

Original languageEnglish
Pages (from-to)287-297
Number of pages11
JournalEuropean Journal of Neuroscience
Issue number2
Publication statusPublished - 2003 Jan
Externally publishedYes


  • Dephosphorylation
  • Fluorescent indicator
  • Long-term potentiation
  • Low-frequency stimulation
  • Phosphatase

ASJC Scopus subject areas

  • General Neuroscience


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