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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.
Abstract:
p35 is an activating co-factor of Cyclin-dependent kinase 5 (Cdk5), a protein whose dysfunction has been implicated in a wide-range of neurological disorders including cognitive impairment and disease. Inducible deletion of the p35 gene in adult mice results in profound deficits in hippocampal-dependent spatial learning and synaptic physiology, however the impact of the loss of p35 function on hippocampal in vivo physiology and spatial coding remains unknown. Here, we recorded CA1 pyramidal cell activity in freely behaving p35 cKO and control mice and found that place cells in the mutant mice have elevated firing rates and impaired spatial coding, accompanied by changes in the temporal organization of spiking both during exploration and rest. These data shed light on the role of p35 in maintaining cellular and network excitability and provide a physiological correlate of the spatial learning deficits in these mice.
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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