Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa 52242, USA.
Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa 52242, USA
Learn Mem. 2024 Jun 14;31(5). doi: 10.1101/lm.053816.123. Print 2024 May.
The common fruit fly provides a powerful platform to investigate the genetic, molecular, cellular, and neural circuit mechanisms of behavior. Research in this model system has shed light on multiple aspects of brain physiology and behavior, from fundamental neuronal function to complex behaviors. A major anatomical region that modulates complex behaviors is the mushroom body (MB). The MB integrates multimodal sensory information and is involved in behaviors ranging from sensory processing/responses to learning and memory. Many genes that underlie brain disorders are conserved, from flies to humans, and studies in have contributed significantly to our understanding of the mechanisms of brain disorders. Genetic mutations that mimic human diseases-such as Fragile X syndrome, neurofibromatosis type 1, Parkinson's disease, and Alzheimer's disease-affect MB structure and function, altering behavior. Studies dissecting the effects of disease-causing mutations in the MB have identified key pathological mechanisms, and the development of a complete connectome promises to add a comprehensive anatomical framework for disease modeling. Here, we review models of human neurodevelopmental and neurodegenerative disorders via the effects of their underlying mutations on MB structure, function, and the resulting behavioral alterations.
常见的果蝇为研究行为的遗传、分子、细胞和神经回路机制提供了一个强大的平台。该模型系统的研究揭示了从基本神经元功能到复杂行为的多个方面的大脑生理学和行为。调节复杂行为的一个主要解剖区域是蘑菇体（MB）。MB 整合了多种感觉信息，参与了从感觉处理/反应到学习和记忆的各种行为。从苍蝇到人，许多导致大脑疾病的基因是保守的，并且在 中的研究极大地促进了我们对大脑疾病机制的理解。模拟人类疾病的遗传突变，如脆性 X 综合征、1 型神经纤维瘤病、帕金森病和阿尔茨海默病，会影响 MB 的结构和功能，从而改变行为。对 MB 中致病突变影响的研究，确定了关键的病理机制，而完整连接组的开发有望为疾病建模增加一个全面的解剖框架。在这里，我们通过其潜在突变对 MB 结构、功能和由此产生的行为改变的影响，来回顾人类神经发育和神经退行性疾病的 模型。
