神经科学-自然2013-09-05 2:58 AM

Circuit level defects in the developing neocortex of Fragile X mice : Nature Neuroscience : Nature Publishing Group

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.

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

神经科学-自然

0 Following 1 Fans 0 Projects 88 Articles

SIMILAR ARTICLES

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease whose causes are still poorly understood. To identify additional genetic

Read More

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease whose causes are still poorly understood. To identify additional genetic

Read More

Large excitatory synapses with multiple active zones ensure reliable and fast information transfer at specific points in neuronal circuits. However, th

Read More

Large excitatory synapses with multiple active zones ensure reliable and fast information transfer at specific points in neuronal circuits. However, th

Read More

Reverse signaling via members of the tumor necrosis factor (TNF) superfamily controls multiple aspects of immune function. Here we document TNFα revers

Read More

Reverse signaling via members of the tumor necrosis factor (TNF) superfamily controls multiple aspects of immune function. Here we document TNFα revers

Read More

The activity-regulated cytoskeletal protein Arc (also known as Arg3.1) is required for long-term memory formation and synaptic plasticity. Arc expressi

Read More

The activity-regulated cytoskeletal protein Arc (also known as Arg3.1) is required for long-term memory formation and synaptic plasticity. Arc expressi

Read More

The vertebrate brain is anatomically and functionally asymmetric. The left and right cerebral hemispheres harbor neural stem cell niches at the ventric

Read More

The vertebrate brain is anatomically and functionally asymmetric. The left and right cerebral hemispheres harbor neural stem cell niches at the ventric

Read More