University of Texas, Department of Neuroscience details research in Fragile X syndrome genetics
December 22nd, 2008
2008 DEC 22 -- Researchers detail in 'Imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of fragile X syndrome,' new data in fragile X syndrome. "Despite the pronounced neurological deficits associated with mental retardation and autism, it is unknown if altered neocortical circuit function occurs in these prevalent disorders. Here we demonstrate specific alterations in local synaptic connections, membrane excitability, and circuit activity of defined neuron types in sensory neocortex of the mouse model of Fragile X Syndrome-the Fmr1 knockout (KO)," scientists in the United States report.
"Overall, these alterations result in hyperexcitability of neocortical circuits in the Fmr1 KO. Specifically, we observe a substantial deficit in local excitatory drive (approximately 50%) targeting fast-spiking (FS) inhibitory neurons in layer 4 of somatosensory, barrel cortex. This persists until at least 4 wk of age suggesting it may be permanent. In contrast, monosynaptic GABAergic synaptic transmission was unaffected. Overall, these changes indicate that local feedback inhibition in neocortical layer 4 is severely impaired in the Fmr1 KO mouse. An increase in the intrinsic membrane excitability of excitatory neurons may further contribute to hyperexcitability of cortical networks. In support of this idea, persistent neocortical circuit activity, or UP states, elicited by thalamic stimulation was longer in duration in the Fmr1 KO mouse. In addition, network inhibition during the UP state was less synchronous, including a 14% decrease in synchrony in the gamma frequency range (30-80 Hz)," wrote J.R. Gibson and colleagues, University of Texas, Department of Neuroscience.
The researchers concluded: "These circuit changes may be involved in sensory stimulus hypersensitivity, epilepsy, and cognitive impairment associated with Fragile X and autism."
Gibson and colleagues published their study in the Journal of Neurophysiology (Imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of fragile X syndrome. Journal of Neurophysiology, 2008;100(5):2615-26).
For more information, contact J.R. Gibson, University of Texas, Dept. of Neuroscience, Southwestern Medical Center, Box 9111, Dallas, TX 75390-9111 USA..
Publisher contact information for the Journal of Neurophysiology is: American Physiological Society, 9650 Rockville Pike, Bethesda, MD 20814, USA.
Keywords: United States, Box, Fragile X Syndrome Genetics, Autism, Developmental Disabilities, Fragile X Syndrome, Genetics, Mental Retardation, Neurology, Neurophysiology, Neuroscience, Physiology.
This article was prepared by Mental Health Weekly Digest editors from staff and other reports. Copyright 2008, Mental Health Weekly Digest via NewsRx.com.
