Circuit level defects in the developing neocortex of Fragile X mice

J. Tiago Goncalves, James E. Anstey, Peyman Golshani, Carlos Portera-Cailliau

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Subtle alterations in how cortical network dynamics are modulated by different behavioral states could disrupt normal brain function and underlie symptoms of neuropsychiatric disorders, including Fragile X syndrome (FXS). Using two-photon calcium imaging and electrophysiology, we recorded spontaneous neuronal ensemble activity in mouse somatosensory cortex. Unanesthetized Fmr1?/? mice exhibited abnormally high synchrony of neocortical network activity, especially during the first two postnatal weeks. Neuronal firing rates were threefold higher in Fmr1?/? mice than in wild-type mice during whole-cell recordings manifesting Up/Down states (slow-wave sleep, quiet wakefulness), probably as a result of a higher firing probability during Up states. Combined electroencephalography and calcium imaging experiments confirmed that neurons in mutant mice had abnormally high firing and synchrony during sleep. We conclude that cortical networks in FXS are hyperexcitable in a brain state-dependent manner during a critical period for experience-dependent plasticity. These state-dependent network defects could explain the intellectual, sleep and sensory integration dysfunctions associated with FXS.

Original languageEnglish (US)
Pages (from-to)903-909
Number of pages7
JournalNature Neuroscience
Volume16
Issue number7
DOIs
StatePublished - 2013
Externally publishedYes

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Neocortex
Fragile X Syndrome
Sleep
Calcium
Somatosensory Cortex
Wakefulness
Electrophysiology
Brain
Patch-Clamp Techniques
Photons
Electroencephalography
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Circuit level defects in the developing neocortex of Fragile X mice. / Goncalves, J. Tiago; Anstey, James E.; Golshani, Peyman; Portera-Cailliau, Carlos.

In: Nature Neuroscience, Vol. 16, No. 7, 2013, p. 903-909.

Research output: Contribution to journalArticle

Goncalves, JT, Anstey, JE, Golshani, P & Portera-Cailliau, C 2013, 'Circuit level defects in the developing neocortex of Fragile X mice', Nature Neuroscience, vol. 16, no. 7, pp. 903-909. https://doi.org/10.1038/nn.3415
Goncalves, J. Tiago ; Anstey, James E. ; Golshani, Peyman ; Portera-Cailliau, Carlos. / Circuit level defects in the developing neocortex of Fragile X mice. In: Nature Neuroscience. 2013 ; Vol. 16, No. 7. pp. 903-909.
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