Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku, Tokyo, 162-0056, Japan.
Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku, Tokyo, 162-0056, Japan.
Mol Brain. 2022 Apr 28;15(1):37. doi: 10.1186/s13041-022-00922-x.
Cyclin-dependent kinase 5 (Cdk5) /p35 is involved in many developmental processes of the central nervous system. Cdk5/p35 is also implicated in synaptic plasticity, learning and memory. Several lines of conditional Cdk5 knockout mice (KO) have been generated and have shown different outcomes for learning and memory. Here, we present our analysis of p35 conditional KO mice (p35cKO) in hippocampal pyramidal neurons or forebrain GABAergic neurons using electrophysiological and behavioral methods. In the fear conditioning task, CamKII-p35cKO mice showed impaired memory retention. Furthermore, NMDAR-dependent long-term depression (LTD) induction by low-frequency stimuli in hippocampal slices from CamkII-p35cKO mice was impaired compared to that in control mice. In contrast, Dlx-p35cKO mice showed no abnormalities in behavioral tasks and electrophysiological analysis in their hippocampal slices. These results indicated that Cdk5/p35 in excitatory neurons is important for the hippocampal synaptic plasticity and associative memory retention.
周期蛋白依赖性激酶 5（Cdk5）/p35 参与中枢神经系统的许多发育过程。Cdk5/p35 也与突触可塑性、学习和记忆有关。已经产生了几种条件性 Cdk5 敲除小鼠（KO），它们在学习和记忆方面表现出不同的结果。在这里，我们使用电生理和行为方法分析了在海马锥体神经元或前脑 GABA 能神经元中条件性敲除 p35 的小鼠（p35cKO）。在恐惧条件反射任务中，CamKII-p35cKO 小鼠表现出记忆保留受损。此外，与对照小鼠相比，来自 CamKII-p35cKO 小鼠的海马切片中低频刺激诱导的 NMDAR 依赖性长时程抑制（LTD）诱导受损。相比之下，Dlx-p35cKO 小鼠在行为任务和海马切片的电生理分析中没有异常。这些结果表明，兴奋性神经元中的 Cdk5/p35 对于海马突触可塑性和联想性记忆保留很重要。
