Activity-dependent FMRP Requirements in Development of the Neural Circuitry of Learning and Memory

Overview

Journal Development

Specialty Biology

Date 2015 Mar 26

PMID 25804740

Citations 40

Authors

Caleb A Doll

Kendal Broadie

Affiliations

Soon will be listed here.

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.

Citing Articles

Neuron-to-glia and glia-to-glia signaling directs critical period experience-dependent synapse pruning.

Nelson N, Miller V, Broadie K Front Cell Dev Biol. 2025; 13:1540052.

PMID: 40040788 PMC: 11876149. DOI: 10.3389/fcell.2025.1540052.

Experience-dependent serotonergic signaling in glia regulates targeted synapse elimination.

Miller V, Broadie K PLoS Biol. 2024; 22(10):e3002822.

PMID: 39352884 PMC: 11444420. DOI: 10.1371/journal.pbio.3002822.

Experience-dependent MAPK/ERK signaling in glia regulates critical period remodeling of synaptic glomeruli.

Baumann N, Sears J, Broadie K Cell Signal. 2024; 120:111224.

PMID: 38740233 PMC: 11459659. DOI: 10.1016/j.cellsig.2024.111224.

Experience-dependent glial pruning of synaptic glomeruli during the critical period.

Nelson N, Vita D, Broadie K Sci Rep. 2024; 14(1):9110.

PMID: 38643298 PMC: 11032375. DOI: 10.1038/s41598-024-59942-3.

Experience-Dependent Remodeling of Juvenile Brain Olfactory Sensory Neuron Synaptic Connectivity in an Early-Life Critical Period.

Nelson N, Miller V, Baumann N, Broadie K J Vis Exp. 2024; (205).

PMID: 38497653 PMC: 11706525. DOI: 10.3791/66629.

References

Das S, Sadanandappa M, Dervan A, Larkin A, Lee J, Sudhakaran I . Plasticity of local GABAergic interneurons drives olfactory habituation. Proc Natl Acad Sci U S A. 2011; 108(36):E646-54. PMC: 3169145. DOI: 10.1073/pnas.1106411108. View

Laissue P, Reiter C, Hiesinger P, Halter S, Fischbach K, Stocker R . Three-dimensional reconstruction of the antennal lobe in Drosophila melanogaster. J Comp Neurol. 1999; 405(4):543-52. View

Packer A, Peterka D, Hirtz J, Prakash R, Deisseroth K, Yuste R . Two-photon optogenetics of dendritic spines and neural circuits. Nat Methods. 2012; 9(12):1202-5. PMC: 3518588. DOI: 10.1038/nmeth.2249. View

Antar L, Dictenberg J, Plociniak M, Afroz R, Bassell G . Localization of FMRP-associated mRNA granules and requirement of microtubules for activity-dependent trafficking in hippocampal neurons. Genes Brain Behav. 2005; 4(6):350-9. DOI: 10.1111/j.1601-183X.2005.00128.x. View

Jones W . The expanding reach of the GAL4/UAS system into the behavioral neurobiology of Drosophila. BMB Rep. 2009; 42(11):705-12. DOI: 10.5483/bmbrep.2009.42.11.705. View

Bongmba O, Martinez L, Elhardt M, Butler K, Tejada-Simon M . Modulation of dendritic spines and synaptic function by Rac1: a possible link to Fragile X syndrome pathology. Brain Res. 2011; 1399:79-95. PMC: 3131096. DOI: 10.1016/j.brainres.2011.05.020. View

Perisse E, Yin Y, Lin A, Lin S, Huetteroth W, Waddell S . Different kenyon cell populations drive learned approach and avoidance in Drosophila. Neuron. 2013; 79(5):945-56. PMC: 3765960. DOI: 10.1016/j.neuron.2013.07.045. View

Tessier C, Broadie K . Molecular and genetic analysis of the Drosophila model of fragile X syndrome. Results Probl Cell Differ. 2011; 54:119-56. PMC: 4936787. DOI: 10.1007/978-3-642-21649-7_7. View

Comery T, Harris J, Willems P, Oostra B, Irwin S, Weiler I . Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci U S A. 1997; 94(10):5401-4. PMC: 24690. DOI: 10.1073/pnas.94.10.5401. View

10.

Portera-Cailliau C . Which comes first in fragile X syndrome, dendritic spine dysgenesis or defects in circuit plasticity?. Neuroscientist. 2011; 18(1):28-44. DOI: 10.1177/1073858410395322. View

11.

Kelleher 3rd R, Bear M . The autistic neuron: troubled translation?. Cell. 2008; 135(3):401-6. DOI: 10.1016/j.cell.2008.10.017. View

12.

Zhang Y, Bailey A, Matthies H, Renden R, Smith M, Speese S . Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell. 2001; 107(5):591-603. DOI: 10.1016/s0092-8674(01)00589-x. View

13.

Gibson J, Bartley A, Hays S, Huber K . Imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of fragile X syndrome. J Neurophysiol. 2008; 100(5):2615-26. PMC: 2585391. DOI: 10.1152/jn.90752.2008. View

14.

Honjo K, Hwang R, Tracey Jr W . Optogenetic manipulation of neural circuits and behavior in Drosophila larvae. Nat Protoc. 2012; 7(8):1470-8. PMC: 3751580. DOI: 10.1038/nprot.2012.079. View

15.

Ito K, Shinomiya K, Ito M, Armstrong J, Boyan G, Hartenstein V . A systematic nomenclature for the insect brain. Neuron. 2014; 81(4):755-65. DOI: 10.1016/j.neuron.2013.12.017. View

16.

Ferrari F, Mercaldo V, Piccoli G, Sala C, Cannata S, Achsel T . The fragile X mental retardation protein-RNP granules show an mGluR-dependent localization in the post-synaptic spines. Mol Cell Neurosci. 2007; 34(3):343-54. DOI: 10.1016/j.mcn.2006.11.015. View

17.

Fenno L, Yizhar O, Deisseroth K . The development and application of optogenetics. Annu Rev Neurosci. 2011; 34:389-412. PMC: 6699620. DOI: 10.1146/annurev-neuro-061010-113817. View

18.

Selby L, Zhang C, Sun Q . Major defects in neocortical GABAergic inhibitory circuits in mice lacking the fragile X mental retardation protein. Neurosci Lett. 2007; 412(3):227-32. PMC: 1839948. DOI: 10.1016/j.neulet.2006.11.062. View

19.

Inada K, Kohsaka H, Takasu E, Matsunaga T, Nose A . Optical dissection of neural circuits responsible for Drosophila larval locomotion with halorhodopsin. PLoS One. 2012; 6(12):e29019. PMC: 3247229. DOI: 10.1371/journal.pone.0029019. View

20.

Masuyama K, Zhang Y, Rao Y, Wang J . Mapping neural circuits with activity-dependent nuclear import of a transcription factor. J Neurogenet. 2012; 26(1):89-102. PMC: 3357894. DOI: 10.3109/01677063.2011.642910. View