Regulation of hippocampal and behavioral excitability by cyclin-dependent kinase 5

Ammar H. Hawasli, Della Koovakkattu, Kanehiro Hayashi, Anne E. Anderson, Craig M. Powell, Christopher M. Sinton, James A. Bibb, Donald C. Cooper

研究成果: Article

19 引用 (Scopus)

抄録

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase that has been implicated in learning, synaptic plasticity, neurotransmission, and numerous neurological disorders. We previously showed that conditional loss of Cdk5 in adult mice enhanced hippocampal learning and plasticity via modulation of calpain-mediated N-methyl-D-aspartic acid receptor (NMDAR) degradation. In the present study, we characterize the enhanced synaptic plasticity and examine the effects of long-term Cdk5 loss on hippocampal excitability in adult mice. Field excitatory post-synaptic potentials (fEPSPs) from the Schaffer collateral CA1 subregion of the hippocampus (SC/CA1) reveal that loss of Cdk5 altered theta burst topography and enhanced post-tetanic potentiation. Since Cdk5 governs NMDAR NR2B subunit levels, we investigated the effects of long-term Cdk5 knockout on hippocampal neuronal excitability by measuring NMDAR-mediated fEPSP magnitudes and population-spike thresholds. Long-term loss of Cdk5 led to increased Mg2+-sensitive potentials and a lower threshold for epileptiform activity and seizures. Biochemical analyses were performed to better understand the role of Cdk5 in seizures. Induced-seizures in wild-type animals led to elevated amounts of p25, the Cdk5-activating cofactor. Long-term, but not acute, loss of Cdk5 led to decreased p25 levels, suggesting that Cdk5/p25 may be activated as a homeostatic mechanism to attenuate epileptiform activity. These findings indicate that Cdk5 regulates synaptic plasticity, controls neuronal and behavioral stimulus-induced excitability and may be a novel pharmacological target for cognitive and anticonvulsant therapies.

元の言語English
記事番号e5808
ジャーナルPLoS One
4
発行部数6
DOI
出版物ステータスPublished - 2009 6 4
外部発表Yes

Fingerprint

Cyclin-Dependent Kinase 5
cyclin-dependent kinase
Neuronal Plasticity
Plasticity
N-Methylaspartate
aspartic acid
seizures
Synaptic Potentials
Seizures
receptors
long term effects
Hippocampus
learning
Learning
anticonvulsants
calpain
Wild Animals
Calpain
nervous system diseases
Protein-Serine-Threonine Kinases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

これを引用

Hawasli, A. H., Koovakkattu, D., Hayashi, K., Anderson, A. E., Powell, C. M., Sinton, C. M., ... Cooper, D. C. (2009). Regulation of hippocampal and behavioral excitability by cyclin-dependent kinase 5. PLoS One, 4(6), [e5808]. https://doi.org/10.1371/journal.pone.0005808

Regulation of hippocampal and behavioral excitability by cyclin-dependent kinase 5. / Hawasli, Ammar H.; Koovakkattu, Della; Hayashi, Kanehiro; Anderson, Anne E.; Powell, Craig M.; Sinton, Christopher M.; Bibb, James A.; Cooper, Donald C.

:: PLoS One, 巻 4, 番号 6, e5808, 04.06.2009.

研究成果: Article

Hawasli, AH, Koovakkattu, D, Hayashi, K, Anderson, AE, Powell, CM, Sinton, CM, Bibb, JA & Cooper, DC 2009, 'Regulation of hippocampal and behavioral excitability by cyclin-dependent kinase 5', PLoS One, 巻. 4, 番号 6, e5808. https://doi.org/10.1371/journal.pone.0005808
Hawasli AH, Koovakkattu D, Hayashi K, Anderson AE, Powell CM, Sinton CM その他. Regulation of hippocampal and behavioral excitability by cyclin-dependent kinase 5. PLoS One. 2009 6 4;4(6). e5808. https://doi.org/10.1371/journal.pone.0005808
Hawasli, Ammar H. ; Koovakkattu, Della ; Hayashi, Kanehiro ; Anderson, Anne E. ; Powell, Craig M. ; Sinton, Christopher M. ; Bibb, James A. ; Cooper, Donald C. / Regulation of hippocampal and behavioral excitability by cyclin-dependent kinase 5. :: PLoS One. 2009 ; 巻 4, 番号 6.
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