A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep

Ugo Faraguna, Vladyslav V. Vyazovskiy, Aaron B. Nelson, Giulio Tononi, Chiara Cirelli

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

Slow-wave activity (SWA), the EEG power between 0.5 and 4 Hz during non-rapid eye movement (NREM) sleep, is one of the best characterized markers of sleep need, because it increases as a function of preceding waking duration and decreases during sleep, but the underlying mechanisms remain unknown. We hypothesized that SWA is high at sleep onset because it reflects the occurrence, during the previous waking period, of widespread synaptic potentiation in cortical and subcortical areas. Consistent with this hypothesis, we recently showed that the more rats explore, the stronger is the cortical expression of BDNF during wakefulness, and the larger is the increase in SWA during the subsequent sleep period. There is compelling evidence that BDNF plays a causal role in synaptic potentiation, and exogenous application of BDNF in vivo is sufficient to induce long-term increases in synaptic strength. We therefore performed cortical unilateral microinjections of BDNF in awake rats and measured SWA during the subsequent sleep period. SWA during NREM sleep was higher in the injected hemisphere relative to the contralateral one. The effect was reversible within 2 h, and did not occur during wakefulness or rapid eye movement sleep. Asymmetries in NREM SWA did not occur after vehicle injections. Furthermore, microinjections, during wakefulness, of a polyclonal anti-BDNF antibody or K252a, an inhibitor of BDNFTrkB receptors, led to a local SWA decrease during the following sleep period. These effects were also reversible and specific for NREM sleep. These results show a causal link between BDNF expression during wakefulness and subsequent sleep regulation.

Original languageEnglish
Pages (from-to)4088-4095
Number of pages8
JournalJournal of Neuroscience
Volume28
Issue number15
DOIs
Publication statusPublished - Apr 9 2008

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Brain-Derived Neurotrophic Factor
Sleep
Wakefulness
Eye Movements
Microinjections
REM Sleep
Electroencephalography
Anti-Idiotypic Antibodies

Keywords

  • BDNF
  • Cerebral cortex
  • EEG
  • Rat
  • Sleep homeostasis
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep. / Faraguna, Ugo; Vyazovskiy, Vladyslav V.; Nelson, Aaron B.; Tononi, Giulio; Cirelli, Chiara.

In: Journal of Neuroscience, Vol. 28, No. 15, 09.04.2008, p. 4088-4095.

Research output: Contribution to journalArticle

Faraguna, U, Vyazovskiy, VV, Nelson, AB, Tononi, G & Cirelli, C 2008, 'A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep', Journal of Neuroscience, vol. 28, no. 15, pp. 4088-4095. https://doi.org/10.1523/JNEUROSCI.5510-07.2008
Faraguna, Ugo ; Vyazovskiy, Vladyslav V. ; Nelson, Aaron B. ; Tononi, Giulio ; Cirelli, Chiara. / A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 15. pp. 4088-4095.
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