Learning defects in Drosophila growth restricted chico mutants are caused by attenuated adenylyl cyclase activity.
Learning defects in Drosophila growth restricted chico mutants are caused by attenuated adenylyl cyclase activity.
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DOI：
10.1186/s13041-016-0217-3
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发表时间：
2016-04-06
期刊：
影响因子：
3.6
通讯作者：
Saitoe M
中科院分区：
文献类型：
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作者：
Naganos S;Ueno K;Horiuchi J;Saitoe M
胰岛素/胰岛素样生长因子信号传导（IIS）减少是对称性宫内生长迟缓（IUGR）的主要原因，IUGR是产前发育期间细胞增殖的受损，导致整体生长缺陷和智力迟钝。在果蝇中，chico编码唯一的胰岛素受体底物。与其他IUGR动物模型相似，chico突变体在整体生长和联想学习方面存在缺陷。然而，chico突变和对称性IUGR引起的学习缺陷的生理和分子基础尚不清楚。在这项研究中，我们发现chico突变损害了蘑菇体（MB）中与记忆相关的突触可塑性，蘑菇体是嗅觉学习的神经中心。奇科突变减少了芜菁型腺苷酸环化酶（rut）的表达，导致MB中cAMP合成减少。在MB中表达rut+转基因可以恢复chico突变体的记忆相关可塑性和嗅觉联想学习，而不影响生长。因此，chico突变至少部分地通过减少MB中的cAMP信号传导来破坏嗅觉学习。我们的研究结果表明，与IIS减少相关的一些认知缺陷可能会发生，独立于发育缺陷，从cAMP信号的急性减少。
Reduced insulin/insulin-like growth factor signaling (IIS) is a major cause of symmetrical intrauterine growth retardation (IUGR), an impairment in cell proliferation during prenatal development that results in global growth defects and mental retardation. In Drosophila, chico encodes the only insulin receptor substrate. Similar to other animal models of IUGR, chico mutants have defects in global growth and associative learning. However, the physiological and molecular bases of learning defects caused by chico mutations, and by symmetrical IUGR, are not clear. In this study, we found that chico mutations impair memory-associated synaptic plasticity in the mushroom bodies (MBs), neural centers for olfactory learning. Mutations in chico reduce expression of the rutabaga-type adenylyl cyclase (rut), leading to decreased cAMP synthesis in the MBs. Expressing a rut+ transgene in the MBs restores memory-associated plasticity and olfactory associative learning in chico mutants, without affecting growth. Thus chico mutations disrupt olfactory learning, at least in part, by reducing cAMP signaling in the MBs. Our results suggest that some cognitive defects associated with reduced IIS may occur, independently of developmental defects, from acute reductions in cAMP signaling.