title: Activity-induced Nr4a1 regulates spine density and distribution pattern of excitatory synapses in pyramidal neurons.
abstract: Excitatory synapses occur mainly on dendritic spines, and spine density is usually correlated with the strength of excitatory synaptic transmission. We report that Nr4a1, an activity-inducible gene encoding a nuclear receptor, regulates the density and distribution of dendritic spines in CA1 pyramidal neurons. Nr4a1 overexpression resulted in elimination of the majority of spines; however, postsynaptic densities were preserved on dendritic shafts, and the strength of excitatory synaptic transmission was unaffected, showing that excitatory synapses can be dissociated from spines. mRNA expression profiling studies suggest that Nr4a1-mediated transcriptional regulation of the actin cytoskeleton contributes to this effect. Under conditions of chronically elevated activity, when Nr4a1 was induced, Nr4a1 knockdown increased the density of spines and PSDs specifically at the distal ends of dendrites. Thus, Nr4a1 is a key component of an activity-induced transcriptional program that regulates the density and distribution of spines and synapses.
authors: Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA.
authors: Yelin
authors: Y
authors: Chen
authors: Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA.
authors: Yuanyuan
authors: Y
authors: Wang
authors: Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA.
authors: Ali
authors: A
authors: Ertürk
authors: Department of Biomedical Imaging, Genentech Inc, South San Francisco, CA 94080, USA.
authors: Dara
authors: D
authors: Kallop
authors: Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA.
authors: Zhiyu
authors: Z
authors: Jiang
authors: Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA; Department of Biomedical Imaging, Genentech Inc, South San Francisco, CA 94080, USA.
authors: Robby M
authors: RM
authors: Weimer
authors: Department of Bioinformatics & Computational Biology, Genentech Inc, South San Francisco, CA 94080, USA.
authors: Joshua
authors: J
authors: Kaminker
authors: Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA. Electronic address: sheng.morgan@gene.com.
authors: Morgan
authors: M
authors: Sheng
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1