Osuka Tomoki, Yamamoto Hiroki, Yagi Takeshi
KOKORO-Biology Group, Laboratories for Integrated Biology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, 565-0871, Japan.
Sci Rep. 2025 Jun 2;15(1):19334. doi: 10.1038/s41598-025-02546-2.
Clustered protocadherins (cPcdh) are cell adhesion molecules with 58 isoforms, essential for neural circuit formation and higher cognitive functions. This study investigated the impact of reduced cPcdh-α diversity on cognitive function using mutant mice. Behavioral tests revealed that cPcdh-α1-12 mice exhibited specific memory impairments ranging from a few seconds to 2 h short-term memory, while memory from 24 h to 2 weeks long-term memory remained intact. Notably, no abnormalities in appearance or spontaneous behavior were observed in cPcdh-α1-12 mice, suggesting that the deficits were specific to short-term memory. Furthermore, a comprehensive analysis of neural activity during memory recall in 2 h short-term memory and 24 h long-term memory following showed significant reductions in the hippocampus, amygdala, and retrosplenial cortex during short-term memory tasks. No such reductions were observed during long-term memory recall. These results suggest that short-term and long-term memory are supported by partially distinct neural circuits and underscore the critical role of cPcdh-α diversity in establishing the neural pathways necessary for short-term memory retrieval.
成簇原钙黏蛋白（cPcdh）是一类具有58种异构体的细胞黏附分子，对神经回路形成和高级认知功能至关重要。本研究使用突变小鼠探究了cPcdh-α多样性降低对认知功能的影响。行为测试表明，cPcdh-α1-12小鼠表现出特定的记忆障碍，从几秒到2小时的短期记忆均受影响，而24小时到2周的长期记忆则保持完好。值得注意的是，cPcdh-α1-12小鼠在外观或自发行为上未观察到异常，这表明这些缺陷是短期记忆所特有的。此外，对2小时短期记忆和24小时长期记忆回忆过程中的神经活动进行全面分析后发现，在短期记忆任务期间，海马体、杏仁核和压后皮质的神经活动显著减少。在长期记忆回忆过程中未观察到此类减少。这些结果表明，短期记忆和长期记忆由部分不同的神经回路支持，并强调了cPcdh-α多样性在建立短期记忆检索所需神经通路中的关键作用。
