Inducible Knockout of the Cyclin-Dependent Kinase 5 Activator p35 Alters Hippocampal Spatial Coding and Neuronal

Eriko Kamiki1,2, Roman Boehringer2, Denis Polygalov2

  • 1Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan.

Insights

Loss of p35 impairs spatial learning by altering hippocampal place cell activity and temporal coding in mice. This highlights p35

Area of Science:

  • Neuroscience
  • Cell Biology

Background:

  • Cyclin-dependent kinase 5 (Cdk5) dysfunction is linked to neurological disorders.
  • p35 acts as an activating co-factor for Cdk5.
  • Previous studies show p35 deletion causes spatial learning deficits.

Purpose of the Study:

  • To investigate the impact of p35 loss on hippocampal in vivo physiology.
  • To understand the effects on spatial coding in freely behaving mice.

Main Methods:

  • Recorded CA1 pyramidal cell activity in p35 conditional knockout (cKO) and control mice.
  • Analyzed place cell firing rates and spatial information.
  • Examined temporal organization of neural spiking during exploration and rest.

Main Results:

  • p35 cKO mice exhibited elevated place cell firing rates.
  • Spatial coding was impaired in p35-deficient mice.
  • Alterations in spiking temporal organization were observed during both activity and rest.

Conclusions:

  • p35 is crucial for maintaining hippocampal cellular and network excitability.
  • The observed physiological changes provide a correlate for spatial learning deficits in p35-deficient mice.

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