PSD-95-nNOS Coupling Regulates Contextual Fear Extinction in the Dorsal CA3

Scientific Reports
Cheng-Yun CaiDong-Ya Zhu

Abstract

Fear extinction depends on N-methyl-D-aspartate glutamate receptors (NMDARs) and brain-derived neurotrophic factor (BDNF) activation in the limbic system. However, postsynaptic density-95 (PSD-95) and neuronal nitric oxide synthase (nNOS) coupling, the downstream signaling of NMDARs activation, obstructs the BDNF signaling transduction. Thus, we wondered distinct roles of NMDAR activation and PSD-95-nNOS coupling on fear extinction. To explore the mechanisms, we detected protein-protein interaction using coimmunoprecipitation and measured protein expression by western blot. Contextual fear extinction induced a shift from PSD-95-nNOS to PSD-95-TrkB association in the dorsal hippocampus and c-Fos expression in the dorsal CA3. Disrupting PSD-95-nNOS coupling in the dorsal CA3 up-regulated phosphorylation of extracellular signal-regulates kinase (ERK) and BDNF, enhanced the association of BDNF-TrkB signaling with PSD-95, and promoted contextual fear extinction. Conversely, blocking NMDARs in the dorsal CA3 down-regulated BDNF expression and hindered contextual fear extinction. NMDARs activation and PSD-95-nNOS coupling play different roles in modulating contextual fear extinction in the hippocampus. Because inhibitors of PSD-95-nNO...Continue Reading

References

Jun 1, 2002·Science·Kazu NakazawaSusumu Tonegawa
Nov 7, 2003·The Journal of Biological Chemistry·Kimberly W RainesPaul Shapiro
Aug 7, 2004·Brain Research. Brain Research Reviews·Teige P SheehanDavid S Russell
Jan 27, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Agnès GruartJosé M Delgado-García
May 23, 2007·Nature Neuroscience·Akira Yoshii, Martha Constantine-Paton
Jul 17, 2007·Nature Neuroscience·Farahnaz SananbenesiLi-Huei Tsai
Sep 21, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Gregory J Quirk, Devin Mueller
Oct 13, 2007·Neurobiology of Learning and Memory·Michael R Hunsaker, Raymond P Kesner
Jun 3, 2009·Behavioral Neuroscience·Michael R HunsakerRaymond P Kesner
Feb 10, 2010·Cell·Henry G S Martin, Yu Tian Wang
Jun 5, 2010·Science·Jamie PetersGregory J Quirk
Oct 28, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Xindao HuErik W Dent
Nov 29, 2011·Trends in Neurosciences·Natalie C TronsonJelena Radulovic
Mar 1, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Marika V DoucetAndrew Harkin
May 3, 2013·Nature Reviews. Neuroscience·Stephen MarenIsrael Liberzon
Dec 24, 2013·Neuron·Judit K Makara, Jeffrey C Magee
Apr 25, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·James M OtisDevin Mueller
Aug 30, 2014·Journal of Psychiatric Research·Elizabeth D BallardCarlos A Zarate
Oct 3, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sarah N GarfinkelIsrael Liberzon
Oct 3, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chun-Xia LuoDong-Ya Zhu
Mar 10, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Lorenz DeutschenbaurUndine E Lang
May 15, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Abhik SenDaniel L Alkon
Jun 25, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Stephen Maren, Andrew Holmes
May 27, 2017·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Brian E BernierMichael R Drew

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Citations

Jan 17, 2019·Cell and Tissue Research·Samia R L JocaGregers Wegener

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Methods Mentioned

BETA
gene knock-out
acetylation
coimmunoprecipitation

Software Mentioned

Freezescan

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