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Cdk5/p35 functions as a crucial regulator of spatial learning and memory
Tomohide Mishiba1, Mika Tanaka2, Naoki Mita3
1Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, , Shinjuku-ku, Tokyo, 162-8480, Japan. sprewell-tomo348@akane.waseda.jp.
Molecular Brain
|November 19, 2014
Summary
Cyclin-dependent kinase 5 (Cdk5) and its activator p35 are crucial for learning and memory. Inducible knockout of p35 in adult mice impaired spatial memory and reduced anxiety, highlighting Cdk5/p35
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Science
Background:
- Cyclin-dependent kinase 5 (Cdk5), activated by p35/p39, plays a role in synaptic plasticity, learning, and memory.
- Previous studies using constitutive knockout models showed severe developmental defects, confounding higher brain function analysis.
- Inducible CreER-p35 conditional knockout (cKO) mice were generated to specifically investigate Cdk5/p35's role in adult brain function.
Purpose of the Study:
- To elucidate the specific role of the Cdk5/p35 complex in higher brain functions, particularly learning and memory.
- To circumvent developmental issues associated with constitutive Cdk5 or p35 knockout.
Main Methods:
- Generation of inducible CreER-p35 conditional knockout (cKO) mice.
- Assessment of spatial learning and memory using behavioral tests.
- Analysis of anxiety-like behavior.
- Evaluation of dendritic spine density in CA1 pyramidal neurons.
- Investigation of long-term depression (LTD) induction in the hippocampus.
Main Results:
- Inducible deletion of p35 in adult mice led to significant spatial learning and memory impairments.
- cKO mice displayed reduced anxiety-like behavior.
- These behavioral deficits correlated with decreased dendritic spine density in hippocampal CA1 neurons.
- Defective long-term depression (LTD) induction was observed in the hippocampus of cKO mice.
Conclusions:
- Cdk5/p35 signaling is essential for maintaining spatial learning and memory functions in adult mice.
- The observed impairments are linked to structural and functional alterations in hippocampal neurons.
- Cdk5/p35 represents a potential therapeutic target for neurological disorders affecting cognitive function.
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