title: Genetic rescue of functional senescence in synaptic and behavioral plasticity.
abstract: OBJECTIVE
  Aging has been linked with decreased neural plasticity and memory formation in humans and in laboratory model species such as the fruit fly, Drosophila melanogaster. Here, we examine plastic responses following social experience in Drosophila as a high-throughput method to identify interventions that prevent these impairments.
  
  
  METHODS
  Wild-type and transgenic Drosophila melanogaster.
  
  
  METHODS
  Young (5-day old) or aged (20-day old) adult female Drosophila were housed in socially enriched (n = 35-40) or isolated environments, then assayed for changes in sleep and for structural markers of synaptic terminal growth in the ventral lateral neurons (LNVs) of the circadian clock.
  
  
  RESULTS
  When young flies are housed in a socially enriched environment, they exhibit synaptic elaboration within a component of the circadian circuitry, the LNVs, which is followed by increased sleep. Aged flies, however, no longer exhibit either of these plastic changes. Because of the tight correlation between neural plasticity and ensuing increases in sleep, we use sleep after enrichment as a high-throughput marker for neural plasticity to identify interventions that prolong youthful plasticity in aged flies. To validate this strategy, we find three independent genetic manipulations that delay age-related losses in plasticity: (1) elevation of dopaminergic signaling, (2) over-expression of the transcription factor blistered (bs) in the LNVs, and (3) reduction of the Imd immune signaling pathway. These findings provide proof-of-principle evidence that measuring changes in sleep in flies after social enrichment may provide a highly scalable assay for the study of age-related deficits in synaptic plasticity.
  
  
  CONCLUSIONS
  These studies demonstrate that Drosophila provides a promising model for the study of age-related loss of neural plasticity and begin to identify genes that might be manipulated to delay the onset of functional senescence.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Donlea
authors.forename: Narendrakumar
authors.initials: N
authors.lastname: Ramanan
authors.forename: Neal
authors.initials: N
authors.lastname: Silverman
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Shaw
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D001681:Biological Assay; D015415:Biomarkers; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D059290:Dopaminergic Neurons / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics* / Q000502:physiology*; D005260:Female; D057166:High-Throughput Screening Assays; D007109:Immunity / Q000235:genetics; D008297:Male; D008568:Memory / Q000502:physiology; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000235:genetics* / Q000502:physiology*; D015203:Reproducibility of Results; D015398:Signal Transduction; D012890:Sleep / Q000502:physiology; D012919:Social Behavior; D012934:Social Isolation; D013569:Synapses / Q000502:physiology; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D029721:Drosophila Proteins; C118897:peptidoglycan recognition protein
keywords: Drosophila; aging; plasticity