Activity-dependent FMRP requirements in development of the neural circuitry of learning and memory
Activity-dependent FMRP requirements in development of the neural circuitry of learning and memory
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DOI：
10.1242/dev.117127
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发表时间：
2015-04-01
期刊：
影响因子：
4.6
通讯作者：
Broadie, Kendal
中科院分区：
文献类型：
--
作者：
Doll, Caleb A.;Broadie, Kendal
在大脑发育的关键时期，神经回路连接的活动依赖性细化对于优化行为表现至关重要。我们假设这一机制在脆性X综合征（FXS）中是有缺陷的，脆性X综合征是智力残疾和自闭症谱系障碍的主要遗传原因。在这里，我们在果蝇FXS疾病模型中使用光遗传学工具来测试蘑菇体（MB）学习和记忆脑中心的两个外部神经元中的活性依赖性树突发生：（1）输入投射神经元（PN），其支配MB萼微肾小球中的Kenyon细胞（KC）;以及（2）输出MVP 2神经元，其由MB脚中的KC支配。输入和输出神经元类表现出独特的活动依赖性的关键期树突重塑。MVP 2乔木扩大果蝇突变体无效脆性X智力低下1（dfmr 1），以及以下通道视紫红质驱动的去极化在关键时期的发展，但减少盐视紫红质驱动的超极化。光遗传学操纵的PN导致相反的结果-减少的树突状乔木以下通道视紫红质去极化和扩大的乔木以下盐视紫红质超极化在发展过程中。重要的是，两类神经元的活性依赖性树突发生在一个发育窗口期间绝对需要dfmr 1。这些结果表明，dfmr 1的行为在神经元类型特异性的活动依赖的方式在果蝇大脑中的学习和记忆回路的早期使用，关键时期的发展过程中，雕刻树突状乔木。
The activity-dependent refinement of neural circuit connectivity during critical periods of brain development is essential for optimized behavioral performance. We hypothesize that this mechanism is defective in fragile X syndrome (FXS), the leading heritable cause of intellectual disability and autism spectrum disorders. Here, we use optogenetic tools in the Drosophila FXS disease model to test activity-dependent dendritogenesis in two extrinsic neurons of the mushroom body (MB) learning and memory brain center: (1) the input projection neuron (PN) innervating Kenyon cells (KCs) in the MB calyx microglomeruli and (2) the output MVP2 neuron innervated by KCs in the MB peduncle. Both input and output neuron classes exhibit distinctive activity-dependent critical period dendritic remodeling. MVP2 arbors expand in Drosophila mutants null for fragile X mental retardation 1 (dfmr1), as well as following channelrhodopsin-driven depolarization during critical period development, but are reduced by halorhodopsin-driven hyperpolarization. Optogenetic manipulation of PNs causes the opposite outcome - reduced dendritic arbors following channelrhodopsin depolarization and expanded arbors following halorhodopsin hyperpolarization during development. Importantly, activity-dependent dendritogenesis in both neuron classes absolutely requires dfmr1 during one developmental window. These results show that dfmr1 acts in a neuron type-specific activity-dependent manner for sculpting dendritic arbors during early-use, critical period development of learning and memory circuitry in the Drosophila brain.