NDLI: Altered Neocortical Rhythmic Activity States in Fmr1 KO mice are Due to Enhanced mGluR5 Signaling and Involve Changes in Excitatory Circuitry

Content Provider	PubMed Central
Author	Hays, Seth A. Huber, Kimberly M. Gibson, Jay R.
Abstract	Despite the pronounced neurological deficits associated with mental retardation and autism, the degree to which neocortical circuit function is altered remains unknown. Here, we study changes in neocortical network function in the form of persistent activity states in the mouse model of Fragile X Syndrome – the Fmr1 knockout (KO). Persistent activity states, or UP states, in the neocortex underlie the slow oscillation which occurs predominantly during slow wave sleep, but may also play a role during awake states. We show that spontaneously occurring UP states in the primary somatosensory cortex are 38-67% longer in Fmr1 KO slices. In vivo, UP states re-occur with a clear rhythmic component consistent with that of the slow oscillation and are similarly longer in the Fmr1 KO. Changes in neocortical excitatory circuitry likely play the major role in this alteration as supported by 3 findings: 1) longer UP states occur in slices of isolated neocortex, 2) pharmacologically isolated excitatory circuits in Fmr1 KO neocortical slices display prolonged bursting states, and 3) selective deletion of Fmr1 in cortical excitatory neurons is sufficient to cause prolonged UP states whereas deletion in inhibitory neurons has no effect. Excess signaling mediated by the group 1 glutamate metabotropic receptor, mGluR5, contributes to the longer UP states. Genetic reduction or pharmacological blockade of mGluR5 rescues the prolonged UP state phenotype. Our results reveal an alteration in network function in a mouse model of intellectual disability and autism which may impact both slow wave sleep and information processing during waking states.
Related Links	http://dx.doi.org/10.1523/jneurosci.3157-11.2011
Ending Page	14234
Page Count	12
Starting Page	14223
File Format	PDF
ISSN	02706474
e-ISSN	15292401
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience
Issue Number	40
Volume Number	31
Language	English
Publisher Date	2011-10-05
Access Restriction	Open
Subject Keyword	Neuroscience(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience

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