嘉 宾 Dr. Yelin Chen (Department of Neuroscience, Genentech Inc, Roche Group, South San Francisco)
题 目 Activity-induced Nr4a1 regulates density and distribution pattern of dendritic spines in CA1
pyramidal neurons
时 间 2013年7月15日 星期一 14:00
地 点 E-104
Abstract:
The majority of excitatory synapses are located on dendritic spines, and spine density is positively correlated with the strength of excitatory synaptic transmission. Here I show an intriguing dissociation between spine and excitatory synapse mediated by an activity-controlled nuclear receptor, Nr4a1. In CA1 pyramidal/excitatory neurons, Nr4a1 overexpression eliminated the majority of spines, but postsynaptic densities (PSDs) were preserved on the dendritic shaft and the strength of excitatory synaptic transmission was unaffected, suggesting excitatory synapses can be dissociated from spines. Mutagenesis and mRNA profiling studies suggested transcriptional regulation of Plk2 and Rac1/RhoA pathways by Nr4a1 as the mechanism. Nr4a1 knockdown had no obvious effects under basal conditions, but, elevated neuronal activity increased the density of synapse/spine at the distal ends of dendrites and impaired synaptic function. These findings implicate Nr4a1 as a key component of an activity-induced feedback mechanism to prevent excessive accumulation of synapse/spine at the distal ends of dendrites.
