Deletion of Fmr1 from Forebrain Excitatory Neurons Triggers Abnormal Cellular, EEG, and Behavioral Phenotypes in the Auditory Cortex of a Mouse Model of Fragile X Syndrome.

Cerebral Cortex
Jonathan W LovelaceKhaleel A Razak

Abstract

Fragile X syndrome (FXS) is a leading genetic cause of autism with symptoms that include sensory processing deficits. In both humans with FXS and a mouse model [Fmr1 knockout (KO) mouse], electroencephalographic (EEG) recordings show enhanced resting state gamma power and reduced sound-evoked gamma synchrony. We previously showed that elevated levels of matrix metalloproteinase-9 (MMP-9) may contribute to these phenotypes by affecting perineuronal nets (PNNs) around parvalbumin (PV) interneurons in the auditory cortex of Fmr1 KO mice. However, how different cell types within local cortical circuits contribute to these deficits is not known. Here, we examined whether Fmr1 deletion in forebrain excitatory neurons affects neural oscillations, MMP-9 activity, and PV/PNN expression in the auditory cortex. We found that cortical MMP-9 gelatinase activity, mTOR/Akt phosphorylation, and resting EEG gamma power were enhanced in CreNex1/Fmr1Flox/y conditional KO (cKO) mice, whereas the density of PV/PNN cells was reduced. The CreNex1/Fmr1Flox/y cKO mice also show increased locomotor activity, but not the anxiety-like behaviors. These results indicate that fragile X mental retardation protein changes in excitatory neurons in the cortex ar...Continue Reading

References

Sep 1, 1992·Human Molecular Genetics·J S SutcliffeS T Warren
Mar 14, 1998·Trends in Neurosciences·V W YongD R Edwards
Aug 10, 2001·Neuroreport·D C RojasR J Hagerman
Sep 8, 2001·Genetics in Medicine : Official Journal of the American College of Medical Genetics·D C CrawfordS L Sherman
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Kimberly M HuberMark F Bear
Nov 9, 2002·Science·Tommaso PizzorussoLamberto Maffei
Apr 23, 2003·Brain Topography·Maija CastrénJuhani Partanen
Mar 24, 2004·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·J ArtiedaJ Iriarte
Jul 16, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lingfei Hou, Eric Klann
Nov 17, 2004·Genes, Brain, and Behavior·Q J YanR P Bauchwitz
Nov 20, 2004·Nature Reviews. Neuroscience·Eric Klann, Thomas E Dever
Nov 27, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lisa A GabelJustin R Fallon
Jan 22, 2005·The Journal of the Acoustical Society of America·David W PurcellTerence W Picton
Jan 22, 2005·The Journal of Biological Chemistry·Jung Jin HwangJae-Young Koh
Aug 9, 2005·Neuroscience and Biobehavioral Reviews·A P Carobrez, L J Bertoglio
Nov 1, 2005·Neurobiology of Disease·E J MientjesB A Oostra
Dec 6, 2006·Genesis : the Journal of Genetics and Development·Sandra GoebbelsKlaus-Armin Nave
May 5, 2007·Annual Review of Genomics and Human Genetics·Olga PenagarikanoStephen T Warren
May 18, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Paulette A McRaeRussell T Matthews
May 23, 2007·Journal of Neuroscience Methods·Eric Maris, Robert Oostenveld
Jan 11, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jennifer A Ronesi, Kimberly M Huber
Apr 11, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Craig A Atencio, Christoph E Schreiner
Feb 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sean B ChristieJustin R Fallon
Feb 26, 2009·Genes & Development·Kyle R LegateReinhard Fässler
Apr 28, 2009·Nature·Jessica A CardinChristopher I Moore
Apr 28, 2009·Nature·Vikaas S SohalKarl Deisseroth
Jan 15, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ali SharmaR Suzanne Zukin
Mar 2, 2010·Neuron·Cristopher M Niell, Michael P Stryker
May 28, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Elizabeth K LucasRita M Cowell
Aug 6, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·John G StrumbosLeonard K Kaczmarek
Aug 20, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lulu Y ChenJulie C Lauterborn
Dec 17, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Carlos J Ballester-RosadoHui-Chen Lu

❮ Previous
Next ❯

Citations

Feb 11, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Elizabeth A McCullaghYuan Wang
Aug 28, 2020·Frontiers in Neuroscience·Jonathan W LovelaceKhaleel A Razak
Dec 8, 2020·Neuroscience and Biobehavioral Reviews·Zachary J WilliamsTiffany G Woynaroski
Sep 26, 2020·Developmental Biology·Sara G SuscoLindy E Barrett
Jul 11, 2021·Brain Research Bulletin·Sam A Booker, Peter C Kind
Oct 15, 2021·Journal of Neurodevelopmental Disorders·Patricia S PirbhoyDevin K Binder

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.