title: Activity-dependent FMRP requirements in development of the neural circuitry of learning and memory.
abstract: 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.
authors: Department of Biological Sciences, Department of Cell and Developmental Biology, The Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University and Medical Center, Nashville, TN 37235, USA.
authors: Caleb A
authors: CA
authors: Doll
authors: Department of Biological Sciences, Department of Cell and Developmental Biology, The Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University and Medical Center, Nashville, TN 37235, USA kendal.broadie@vanderbilt.edu.
authors: Kendal
authors: K
authors: Broadie
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D018390:Gene Targeting; D008568:Memory; D024521:Mushroom Bodies / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009415:Nerve Net / Q000378:metabolism*; D013997:Time Factors
chemical_list: D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; C467328:FMR1 protein, Drosophila
keywords: Channelrhodopsin; Critical period; Dendrite; Drosophila; Fmr1; Fragile X syndrome; Halorhodopsin; Mushroom body; Synapse