Forebrain-specific constitutively active CaMKKα transgenic mice show deficits in hippocampus-dependent long-term memory

Taku Kaitsuka, Sheng Tian Li, Kenji Nakamura, Keizo Takao, Tsuyoshi Miyakawa, Masayuki Matsushita

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The Ca 2+/calmodulin (CaM) kinase cascade is activated by Ca 2+ influx through the voltage-dependent Ca 2+ channels and the NMDA receptor. CaM kinase kinase (CaMKK), the most upstream kinase of the CaM kinase cascade, phosphorylates and activates both CaM kinase I (CaMKI) and CaMKIV, resulting in activation of cyclic AMP-responsive element binding protein (CREB)-dependent gene transcription. Using transgenic techniques, we created mutant mice in which a constitutively active form of CaMKK1, the autoinhibitory domain truncated protein, is over-expressed specifically in the forebrain. In these mice, although performance was normal in basal activity and short-term memory, specific impairments were shown in hippocampus-dependent long-term memory after training in spatial memory tasks and after contextual fear conditioning. In cultured neurons of these mice, phosphorylation of CaMKI was significantly increased in basal states, whereas the activity range of CaMKI phosphorylation by brain-derived neurotrophic factor (BDNF) and KCl stimulation was significantly diminished in mutant mice. Our results define a critical role for CaMKKα in synaptic plasticity and the retention of hippocampus-dependent long-term memory.

Original languageEnglish
Pages (from-to)238-247
Number of pages10
JournalNeurobiology of Learning and Memory
Volume96
Issue number2
DOIs
Publication statusPublished - 01-09-2011

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Calcium-Calmodulin-Dependent Protein Kinases
Long-Term Memory
Prosencephalon
Transgenic Mice
Calcium-Calmodulin-Dependent Protein Kinase Type 1
Hippocampus
Phosphotransferases
Phosphorylation
Neuronal Plasticity
Brain-Derived Neurotrophic Factor
N-Methyl-D-Aspartate Receptors
Short-Term Memory
Cyclic AMP
Fear
Carrier Proteins
Learning
Neurons
Genes

All Science Journal Classification (ASJC) codes

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

Cite this

Kaitsuka, Taku ; Li, Sheng Tian ; Nakamura, Kenji ; Takao, Keizo ; Miyakawa, Tsuyoshi ; Matsushita, Masayuki. / Forebrain-specific constitutively active CaMKKα transgenic mice show deficits in hippocampus-dependent long-term memory. In: Neurobiology of Learning and Memory. 2011 ; Vol. 96, No. 2. pp. 238-247.
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Forebrain-specific constitutively active CaMKKα transgenic mice show deficits in hippocampus-dependent long-term memory. / Kaitsuka, Taku; Li, Sheng Tian; Nakamura, Kenji; Takao, Keizo; Miyakawa, Tsuyoshi; Matsushita, Masayuki.

In: Neurobiology of Learning and Memory, Vol. 96, No. 2, 01.09.2011, p. 238-247.

Research output: Contribution to journalArticle

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