Loss of serum response factor in mature neurons in the dentate gyrus alters the morphology of dendritic spines and hippocampus-dependent behavioral tasks

Brain Structure & Function
Karolina NaderKatarzyna Kalita

Abstract

Serum response factor (SRF) is a major transcription factor that regulates the expression of several plasticity-associated genes in the brain. Although the developmental expression of SRF in excitatory neurons is crucial for establishing proper hippocampal circuitry, no substantial evidence of its role in unstimulated mature neurons has been provided. The present study used time-controlled, conditional SRF knockout mice and found that the lack of SRF in adult neurons led to decreased actin levels and inactivation of the actin-severing protein cofilin 1 through its increase in phosphorylation at Ser3. The augmentation of cofilin 1 phosphorylation correlated with an alteration of dendritic spine morphology in the dentate gyrus, which was reflected by an increase in the number of spines that clustered into the long-spine category. The changes in spine morphology coincided with a lower amplitude and frequency of miniature excitatory postsynaptic currents. Moreover, SRF knockout animals were hyperactive and exhibited impairments in hippocampus-dependent behaviors, such as digging, marble burying, and nesting. Altogether, our data indicate that the adult deletion of neuronal SRF leads to alterations of spine morphology and function a...Continue Reading

References

Oct 29, 2000·Science·A Matus
Aug 25, 2001·Annual Review of Neuroscience·R Yuste, T Bonhoeffer
Feb 5, 2002·Annual Review of Physiology·Esther A NimchinskyKarel Svoboda
May 9, 2002·Behavioural Brain Research·Robert M J DeaconJ Nicholas P Rawlins
Dec 12, 2002·Molecular Biology of the Cell·Guido PosernRichard Treisman
May 7, 2003·Cell·Francesc MirallesRichard Treisman
Jul 10, 2003·Trends in Neurosciences·Haruo KasaiHiroyuki Nakahara
May 26, 2004·The Journal of Cell Biology·Kyoko Nagata-OhashiKensaku Mizuno
Jul 24, 2004·Trends in Neurosciences·Gerd KempermannGolo Kronenberg
Nov 19, 2004·Human Molecular Genetics·Paolo MorettiHuda Y Zoghbi
Dec 8, 2004·Behavioural Brain Research·Robert M J Deacon, J Nicholas P Rawlins
Apr 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Siegfried AlbertiAlfred Nordheim
May 10, 2005·Nature Neuroscience·Narendrakumar RamananDavid D Ginty
May 11, 2005·Progress in Neurobiology·Iryna M Ethell, Elena B Pasquale
Dec 21, 2005·Genome Research·Qiang SunJoseph M Miano
Jan 18, 2006·Nature Neuroscience·Bernd KnöllAlfred Nordheim
Aug 25, 2006·American Journal of Physiology. Cell Physiology·Joseph M MianoKeigi Fujiwara
Sep 29, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Katarzyna KalitaMichal Hetman
May 15, 2007·Current Opinion in Neurobiology·Jennifer Bourne, Kristen M Harris
Aug 9, 2007·BMC Neuroscience·Gitta ErdmannStefan Berger
Sep 4, 2007·Progress in Brain Research·David G AmaralPierre Lavenex
Apr 22, 2009·The Journal of Cell Biology·Pirta HotulainenPekka Lappalainen
Aug 21, 2009·Nature Reviews. Neuroscience·Anthony Holtmaat, Karel Svoboda
Feb 9, 2010·Trends in Neurosciences·Haruo KasaiJun Noguchi
Mar 13, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jan Rodriguez ParkitnaGünther Schütz
May 6, 2010·European Journal of Human Genetics : EJHG·Richard HoltUNKNOWN EU Autism MOLGEN Consortium
May 12, 2010·The Journal of Cell Biology·Pirta Hotulainen, Casper C Hoogenraad
Feb 19, 2011·Behavioural Brain Research·A W JohnsonN Ramanan
Feb 25, 2011·Nature Neuroscience·Peter PenzesKevin M Woolfrey
Jul 21, 2011·Physiological Genomics·Craig C BensonJoseph M Miano
Sep 8, 2011·Journal of Cell Science·Piotr MichalukJakub Wlodarczyk
Nov 18, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Paul P Y Lu, Narendrakumar Ramanan
Dec 16, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Eva BenitoAngel Barco
May 2, 2012·Neuroscience·J R Glausier, D A Lewis
Aug 28, 2012·BMC Bioinformatics·Błażej RuszczyckiJakub Wlodarczyk
Aug 29, 2012·Proceedings of the National Academy of Sciences of the United States of America·Henning BeckBernd Knöll

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Citations

Jan 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Philip Förstner, Bernd Knöll
Dec 17, 2020·Frontiers in Cell and Developmental Biology·Qiang WangHaifa Qiao

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