PUBLICATION

Circadian and homeostatic regulation of structural synaptic plasticity in hypocretin neurons

Authors
Appelbaum, L., Wang, G., Yokogawa, T., Skariah, G.M., Smith, S.J., Mourrain, P., and Mignot, E.
ID
ZDB-PUB-101011-46
Date
2010
Source
Neuron   68(1): 89-98 (Journal)
Registered Authors
Appelbaum, Lior, Mourrain, Philippe
Keywords
none
MeSH Terms
  • C-Reactive Protein/genetics
  • C-Reactive Protein/metabolism
  • Neuronal Plasticity/genetics
  • Neuronal Plasticity/physiology*
  • Homeostasis/genetics
  • Homeostasis/physiology*
  • Orexins
  • Humans
  • Neuropeptides/metabolism*
  • Zebrafish
  • In Vitro Techniques
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Synapses/genetics
  • Synapses/physiology*
  • Green Fluorescent Proteins/genetics
  • Animals, Genetically Modified
  • Axons/metabolism
  • Behavior, Animal
  • Circadian Rhythm/genetics
  • Circadian Rhythm/physiology*
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Animals
  • Larva
  • Pineal Gland/growth & development
  • Pineal Gland/metabolism
  • Brain/cytology
  • Brain/growth & development
  • Neurons/cytology
  • Neurons/physiology*
  • Light
  • Microscopy, Confocal
  • Melatonin/pharmacology
  • Synaptophysin/metabolism
PubMed
20920793 Full text @ Neuron
Abstract
Neurons exhibit rhythmic activity that ultimately affects behavior such as sleep. In living zebrafish larvae, we used time-lapse two-photon imaging of the presynaptic marker synaptophysin in hypocretin/orexin (HCRT) neurons to determine the dynamics of synaptic modifications during the day and night. We observed circadian rhythmicity in synapse number in HCRT axons. This rhythm is regulated primarily by the circadian clock but is also affected by sleep deprivation. Furthermore, NPTX2, a protein implicated in AMPA receptor clustering, modulates circadian synaptic changes. In zebrafish, nptx2b is a rhythmic gene that is mostly expressed in hypothalamic and pineal gland cells. Arrhythmic transgenic nptx2b overexpression (hcrt:NPTX2b) increases synapse number and abolishes rhythmicity in HCRT axons. Finally, hcrt:NPTX2b fish are resistant to the sleep-promoting effects of melatonin. This behavioral effect is consistent with NPTX2b-mediated increased activity of HCRT circuitry. These data provide real-time in vivo evidence of circadian and homeostatic regulation of structural synaptic plasticity.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Mapping