Circuit level defects in the developing neocortex of Fragile X mice
| Autor: | J. Tiago Gonçalves, Peyman Golshani, James E. Anstey, Carlos Portera-Cailliau |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Patch-Clamp Techniques Action Potentials Neocortex Electroencephalography Somatosensory system Fragile X Mental Retardation Protein Mice GABA 0302 clinical medicine mGluR fragile X syndrome two-photon Neurons 0303 health sciences medicine.diagnostic_test General Neuroscience slow cortical oscillation Age Factors 2-photon Fragile X syndrome calcium imaging medicine.anatomical_structure barrel cortex Female Wakefulness Psychology Mice Transgenic anesthesia patch clamp Article 03 medical and health sciences Calcium imaging wakefulness medicine Animals Humans sleep 030304 developmental biology Analysis of Variance electrophysiology medicine.disease Brain Waves FMR1 Electric Stimulation Mice Inbred C57BL Electrophysiology Logistic Models Animals Newborn Up and Down states network Calcium Nerve Net Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Nature neuroscience |
| ISSN: | 1546-1726 1097-6256 |
| DOI: | 10.1038/nn.3415 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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