Impairment of hippocampal long-term depression and defective spatial learning and memory in p35-/- mice

Toshio Ohshima, Hiroo Ogura, Kazuhito Tomizawa, Kanehiro Hayashi, Hiromi Suzuki, Taro Saito, Hirotsugu Kamei, Akinori Nishi, James A. Bibb, Shin Ichi Hisanaga, Hideki Matsui, Katsuhiko Mikoshiba

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Cdk5 (cyclin-dependent kinase 5) activity is dependent upon association with one of two neuron-specific activators, p35 or p39. Genetic deletion of Cdk5 causes perinatal lethality with severe defects in corticogenesis and neuronal positioning. p35-/- mice are viable with milder histological abnormalities. Although substantial evidence implicates Cdk5 in synaptic plasticity, its role in learning and memory has not been evaluated using mutant mouse models. We report here that p35-/- mice have deficiencies in spatial learning and memory. Close examination of hippocampal circuitry revealed subtle histological defects in CA1 pyramidal cells. Furthermore, p35 -/- mice exhibit impaired long-term depression and depotentiation of long-term potentiation in the Schaeffer collateral CA1 pathway. Moreover, the Cdk5-dependent phosphorylation state of protein phosphatase inhibitor-1 was increased in 4-week-old mice due to increased levels of p39, which colocalized with inhibitor-1 and Cdk5 in the cytoplasm. These results demonstrate that p35-dependent Cdk5 activity is important to learning and synaptic plasticity. Deletion of p35 may shift the substrate specificity of Cdk5 due to compensatory expression of p39.

Original languageEnglish
Pages (from-to)917-925
Number of pages9
JournalJournal of Neurochemistry
Volume94
Issue number4
DOIs
Publication statusPublished - Aug 2005

Fingerprint

Cyclin-Dependent Kinase 5
Depression
Data storage equipment
Neuronal Plasticity
Plasticity
Long-Term Synaptic Depression
Learning
Defects
Phosphorylation
Long-Term Potentiation
Pyramidal Cells
Substrate Specificity
Spatial Memory
Spatial Learning
Neurons
Cytoplasm
Association reactions
Substrates

Keywords

  • Cyclin-dependent kinase 5
  • Long-term depression
  • Long-term potentiation
  • Neuron-specific activators
  • Synaptic plasticity

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Impairment of hippocampal long-term depression and defective spatial learning and memory in p35-/- mice. / Ohshima, Toshio; Ogura, Hiroo; Tomizawa, Kazuhito; Hayashi, Kanehiro; Suzuki, Hiromi; Saito, Taro; Kamei, Hirotsugu; Nishi, Akinori; Bibb, James A.; Hisanaga, Shin Ichi; Matsui, Hideki; Mikoshiba, Katsuhiko.

In: Journal of Neurochemistry, Vol. 94, No. 4, 08.2005, p. 917-925.

Research output: Contribution to journalArticle

Ohshima, T, Ogura, H, Tomizawa, K, Hayashi, K, Suzuki, H, Saito, T, Kamei, H, Nishi, A, Bibb, JA, Hisanaga, SI, Matsui, H & Mikoshiba, K 2005, 'Impairment of hippocampal long-term depression and defective spatial learning and memory in p35-/- mice', Journal of Neurochemistry, vol. 94, no. 4, pp. 917-925. https://doi.org/10.1111/j.1471-4159.2005.03233.x
Ohshima, Toshio ; Ogura, Hiroo ; Tomizawa, Kazuhito ; Hayashi, Kanehiro ; Suzuki, Hiromi ; Saito, Taro ; Kamei, Hirotsugu ; Nishi, Akinori ; Bibb, James A. ; Hisanaga, Shin Ichi ; Matsui, Hideki ; Mikoshiba, Katsuhiko. / Impairment of hippocampal long-term depression and defective spatial learning and memory in p35-/- mice. In: Journal of Neurochemistry. 2005 ; Vol. 94, No. 4. pp. 917-925.
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