Department of Neuroscience, Genentech Inc, South San Francisco, CA 94080, USA.
Department of Biomedical Imaging, Genentech Inc, South San Francisco, CA 94080, USA.
Neuron. 2014 Jul 16;83(2):431-443. doi: 10.1016/j.neuron.2014.05.027. Epub 2014 Jun 26.
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.
兴奋性突触主要发生在树突棘上，而树突棘密度通常与兴奋性突触传递的强度相关。我们报告称，Nr4a1 是一种编码核受体的活性诱导基因，可调节 CA1 锥体神经元树突棘的密度和分布。Nr4a1 的过表达导致大多数棘突的消除；然而，树突干上保留了突触后密度，兴奋性突触传递的强度不受影响，表明兴奋性突触可以与棘突分离。mRNA 表达谱研究表明，Nr4a1 介导的肌动蛋白细胞骨架的转录调控对此有贡献。在活性长期升高的情况下，当 Nr4a1 被诱导时，Nr4a1 的敲低特异性地增加了树突末梢的棘突和 PSD 的密度。因此，Nr4a1 是一种活性诱导的转录程序的关键组成部分，该程序调节棘突和突触的密度和分布。
