Data underlying Fig 4.

Sleep is crucial for cognitive functions and life span across species. While sleep homeostasis and cognitive processes are linked through cellular and synaptic plasticity, the signaling pathways connecting them remain unclear. Here, we show that Drosophila insomniac (inc) short sleep mutants, which lack an adaptor protein for the autism-associated Cullin-3 ubiquitin ligase, exhibited enhanced Pavlovian aversive olfactory learning and memory, unlike other sleep mutants with normal or reduced memory. Through a genetic modifier screen, we found that a mild reduction of Protein Kinase A (PKA) signaling specifically rescued the sleep and longevity phenotypes of inc mutants. However, this reduction further increased their excessive memory and mushroom body overgrowth. Since inc mutants displayed higher PKA signaling, we propose that inc loss-of-function suppresses sleep via increased PKA activity, which also constrains the excessive memory of inc mutants. Our data identify a signaling cascade for balancing sleep and memory functions, and provide a plausible explanation for the sleep phenotypes of inc mutants, suggesting that memory hyperfunction can provoke sleep deficits.

睡眠对于所有物种的认知功能与寿命均至关重要。尽管睡眠稳态与认知过程通过细胞及突触可塑性建立关联，但二者间的信号通路仍未明确。本研究发现，缺乏自闭症相关泛素连接酶Cullin-3（Cullin-3 ubiquitin ligase）衔接蛋白的果蝇失眠（insomniac, inc）短睡眠突变体，其巴甫洛夫厌恶性嗅觉学习与记忆能力显著增强，而其他睡眠突变体的记忆能力则表现正常或受损。通过遗传修饰筛选实验，我们发现轻度下调蛋白激酶A（Protein Kinase A, PKA）信号通路，可特异性挽救inc突变体的睡眠与寿命表型。但该下调操作进一步加剧了突变体的记忆亢进与脑内蕈形体过度增生表型。鉴于inc突变体的PKA信号水平更高，我们提出：inc基因功能缺失通过升高PKA活性抑制睡眠，而该活性升高同时亦可限制inc突变体的记忆亢进表型。本研究数据明确了一条调控睡眠与记忆功能平衡的信号级联通路，为inc突变体的睡眠表型提供了合理的解释，并提示记忆功能亢进可引发睡眠缺陷。