KCl depolarization-regulated genes in mouse cortical neurons
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE11256 | GEO | 2008/09/24
SECONDARY ACCESSION(S): PRJNA109193
REPOSITORIES: GEO
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Project description:we used DNA microarray analysis to identify genes that are induced by neuronal activity in excitatory neurons at the time when inhibitory synapses are forming and maturing on them. Experiment Overall Design: We cultured cortical neurons for 7 DIV until the process of inhibitory synapse development was underway, and then depolarized the neurons with 50 mM of KCl to activate L-type voltage-sensitive calcium channels (L-VSCCs) for 0, 1 or 6 hours, the cells were lysed, mRNA isolated and hybridized to Affymetrix arrays. Data were collected from 3 independent experiments.
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Project description: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. After 10 days in culture, dissociated mouse hippocampal neurons in 6-well plates were infected with lentivirus expressing either Flag-Nr4a1 or GFP and incubated for 6 days to allow for transgene expression. Total RNA was then isolated using RNeasy Plus kit (QIAGEN). Samples passing an mRNA quality check proceeded to quantitative analysis on Agilent-026655 4x44 Mouse Microarrays.
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