Dysregulated Prefrontal Cortex Inhibition in Prepubescent and Adolescent Fragile X Mouse Model

Frontiers in Molecular Neuroscience
Ioannis KramvisRhiannon M Meredith

Abstract

Changes in excitation and inhibition are associated with the pathobiology of neurodevelopmental disorders of intellectual disability and autism and are widely described in Fragile X syndrome (FXS). In the prefrontal cortex (PFC), essential for cognitive processing, excitatory connectivity and plasticity are found altered in the FXS mouse model, however, little is known about the state of inhibition. To that end, we investigated GABAergic signaling in the Fragile X Mental Retardation 1 (FMR1) knock out (Fmr1-KO) mouse medial PFC (mPFC). We report changes at the molecular, and functional levels of inhibition at three (prepubescence) and six (adolescence) postnatal weeks. Functional changes were most prominent during early postnatal development, resulting in stronger inhibition, through increased synaptic inhibitory drive and amplitude, and reduction of inhibitory short-term synaptic depression. Noise analysis of prepubescent post-synaptic currents demonstrated an increased number of receptors opening during peak current in Fmr1-KO inhibitory synapses. During adolescence amplitudes and plasticity changes normalized, however, the inhibitory drive was now reduced in Fmr1-KO, while synaptic kinetics were prolonged. Finally, adolescen...Continue Reading

References

Jun 1, 1994·Current Opinion in Neurobiology·J M Bekkers
Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·M V Tsodyks, H Markram
Aug 17, 1999·Epilepsia·S A MusumeciM Elia
Dec 6, 2000·Brain and Cognition·F MunirJ Wilding
Apr 3, 2001·Annual Review of Neuroscience·E K Miller, J D Cohen
Sep 8, 2001·Nature Neuroscience·K Jensen, I Mody
Feb 5, 2002·Annual Review of Physiology·Robert S Zucker, Wade G Regehr
Apr 5, 2002·Neuropsychologia·John WildingFehmidah Munir
Dec 6, 2002·Journal of Neurophysiology·Matthew I BanksRobert A Pearce
Nov 11, 2003·Genes, Brain, and Behavior·J L R Rubenstein, M M Merzenich
Mar 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·V MenonA L Reiss
Mar 10, 2005·Neuroscience Letters·Abdeslem El IdrissiCarl Dobkin
Apr 2, 2005·Nature Reviews. Neuroscience·Alfons Schnitzler, Joachim Gross
Oct 6, 2006·American Journal of Medical Genetics. Part a·Kelly SullivanDonald Bailey
Oct 19, 2006·Brain Research·Charlotte D'HulstR Frank Kooy
Sep 13, 2007·Nature Reviews. Neuroscience·Clive R Bramham, David G Wells
Nov 22, 2007·Biological Psychiatry·Diego CentonzeClaudia Bagni
Feb 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sean B ChristieJustin R Fallon
Dec 4, 2009·Frontiers in Computational Neuroscience·Alex LoebelMagnus J E Richardson
Jul 2, 2010·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Michel C Van den OeverSabine Spijker
Jan 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dilja D KruegerMark F Bear
Mar 25, 2011·Current Opinion in Neurobiology·Karim BenchenaneFrancesco P Battaglia
Sep 9, 2011·Genome Research·Laetitia DavidovicMarc-Emmanuel Dumas
Jan 18, 2012·The Journal of Physiology·Marlene Bartos, Claudio Elgueta
Mar 28, 2012·Journal of the American Academy of Child and Adolescent Psychiatry·Amy F T Arnsten, Katya Rubia
May 1, 2012·Trends in Neurosciences·Rhiannon M MeredithIoannis Kramvis
Feb 12, 2013·Neuron·Corentin Le Magueresse, Hannah Monyer
Dec 7, 2013·Frontiers in Behavioral Neuroscience·Ioannis KramvisRhiannon Meredith
Jan 16, 2014·The Journal of Biological Chemistry·Christine DixonAngelo Keramidas

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May 15, 2021·Seminars in Cell & Developmental Biology·Kristen DelevichLinda Wilbrecht

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BETA
electrophoresis

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mini Analysis
Synaptosoft
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pClamp
GraphPad Prism
Mathworks
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