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

Intracellular Signaling Peptides and Proteins/metabolism*
Brain/cytology
Brain/growth & development
Synaptophysin/metabolism
Homeostasis/genetics
Homeostasis/physiology*
Zebrafish
Nerve Tissue Proteins/genetics
Nerve Tissue Proteins/metabolism
Microscopy, Confocal
Green Fluorescent Proteins/genetics
Larva
Orexins
Pineal Gland/growth & development
Pineal Gland/metabolism
Behavior, Animal
Light
Neuropeptides/metabolism*
Circadian Rhythm/genetics
Circadian Rhythm/physiology*
Neuronal Plasticity/genetics
Neuronal Plasticity/physiology*
Gene Expression Regulation, Developmental/drug effects
Gene Expression Regulation, Developmental/genetics
Humans
Axons/metabolism
Synapses/genetics
Synapses/physiology*
Animals
Animals, Genetically Modified
C-Reactive Protein/genetics
C-Reactive Protein/metabolism
Neurons/cytology
Neurons/physiology*
In Vitro Techniques
Melatonin/pharmacology

(all 36)

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