Circuit defects in the neocortex of Fmr1 knockout mice

Carlos Portera-Cailliau

Wednesday, March 12, 2014 at 12:00pm
560 Evans Hall

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. We find that unanesthetized Fmr1–/– mice exhibit abnormally high synchrony of neocortical network activity. Neuronal firing rates are also 3-fold higher in Fmr1–/– mice when the animals are in slow wave sleep or quiet wakefulness. Combined EEG/calcium imaging experiments confirmed that neurons in mutant mice have abnormally high firing and synchrony during sleep/rest. 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.