Syngap1 haploinsufficiency damages a postnatal critical period of pyramidal cell structural maturation linked to cortical circuit assembly

Biological Psychiatry
Massimiliano AcetiGavin Rumbaugh

Abstract

Genetic haploinsufficiency of SYNGAP1/Syngap1 commonly occurs in developmental brain disorders, such as intellectual disability, epilepsy, schizophrenia, and autism spectrum disorder. Thus, studying mouse models of Syngap1 haploinsufficiency may uncover pathologic developmental processes common among distinct brain disorders. A Syngap1 haploinsufficiency model was used to explore the relationship between critical period dendritic spine abnormalities, cortical circuit assembly, and the window for genetic rescue to understand how damaging mutations disrupt key substrates of mouse brain development. Syngap1 mutations broadly disrupted a developmentally sensitive period that corresponded to the period of heightened postnatal cortical synaptogenesis. Pathogenic Syngap1 mutations caused a coordinated acceleration of dendrite elongation and spine morphogenesis and pruning of these structures in neonatal cortical pyramidal neurons. These mutations also prevented a form of developmental structural plasticity associated with experience-dependent reorganization of brain circuits. Consistent with these findings, Syngap1 mutant mice displayed an altered pattern of long-distance synaptic inputs into a cortical area important for cognition. I...Continue Reading

References

Feb 26, 2016·Frontiers in Cellular Neuroscience·Nallathambi Jeyabalan, James P Clement
Aug 2, 2015·Neuropharmacology·Kevin K OgdenGavin Rumbaugh
Jul 28, 2016·Biological Psychiatry·Eunee LeeEunjoon Kim
Sep 14, 2016·Journal of Neuroinflammation·Ilse PalmersVeerle Somers
Mar 17, 2018·Nature Reviews. Neuroscience·Marc P ForrestPeter Penzes
Apr 10, 2018·Experimental & Molecular Medicine·Se-Young Choi
Apr 19, 2019·Clinical Dysmorphology·Farah KananiDDD Study
Jun 20, 2019·Psychiatry and Clinical Neurosciences·Jun Nishiyama
Aug 5, 2017·Annual Review of Neuroscience·MacKenzie A Howard, Scott C Baraban
Jun 26, 2018·Pharmacological Reports : PR·Maksym V KopanitsaNoboru H Komiyama
Dec 2, 2016·Frontiers in Cellular Neuroscience·Yu-Chih LinGene J Blatt
Jun 7, 2017·Acta Neuropathologica·Merina VarghesePatrick R Hof
Aug 28, 2019·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Mudit AgarwalCarl E Stafstrom
Sep 13, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Cyril MignotChristel Depienne
Mar 19, 2016·Journal of Medical Genetics·Cyril MignotChristel Depienne

Citations

Mar 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Gavin RumbaughRichard L Huganir
Dec 17, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Holly J CarlisleMary B Kennedy
Jan 16, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Xiaochuan GuoGavin Rumbaugh
Feb 7, 2009·The New England Journal of Medicine·Fadi F HamdanSynapse to Disease Group
Jul 7, 2009·Annual Review of Physiology·D Harshad BhattWen-Biao Gan
Jun 11, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alberto Cruz-MartínCarlos Portera-Cailliau
Aug 5, 2010·American Journal of Medical Genetics. Part a·Ana Cristina V KrepischiAngela M Vianna-Morgante
Sep 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Feng PanWen-Biao Gan
Jan 18, 2011·Biological Psychiatry·Fadi F HamdanJacques L Michaud
Feb 25, 2011·Nature Neuroscience·Peter PenzesKevin M Woolfrey
Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Zdravko PetanjekIvica Kostovic
Oct 18, 2011·Current Opinion in Neurobiology·Chiara Verpelli, Carlo Sala
Apr 17, 2012·Cell·Mathieu Laplante, David M Sabatini
May 1, 2012·Neuron·Ivan IossifovMichael Wigler
Oct 5, 2012·The New England Journal of Medicine·Joep de LigtLisenka E L M Vissers
May 3, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dimitri CloëttaMarkus A Rüegg
May 21, 2013·American Journal of Medical Genetics. Part a·Karin Writzl, Alida C Knegt
Jun 21, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·James P ClementGavin Rumbaugh
Jan 28, 2014·Nature·Menachem FromerMichael C O'Donovan
Jan 28, 2014·Nature·Shaun M PurcellPamela Sklar
May 29, 2014·Nature Neuroscience·Alexander HoischenEvan E Eichler
May 29, 2014·Nature Neuroscience·Xiaolin ZhuDavid B Goldstein

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