Abstract
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.