Genome-Wide Profiling of the Activity-Dependent Hippocampal Transcriptome

Abstract

Activity-dependent gene expression is central for sculpting neuronal connectivity in the brain. Despite the importance for synaptic plasticity, a comprehensive analysis of the temporal changes in the transcriptomic response to neuronal activity is lacking. In a genome wide survey we identified genes that were induced at 1, 4, 8, or 24 hours following neuronal activity in the hippocampus. According to their distinct expression kinetics we assigned these genes to five clusters, each containing approximately 200 genes. Using in situ hybridizations the regulated expression of 24 genes was validated. Apart from known activity-dependent genes our study reveals a large number of unknown induced genes with distinct expression kinetics. Among these we identified several genes with complex temporal expression patterns. Furthermore, our study provides examples for activity-induced exon switching in the coding region of genes and activity-induced alternative splicing of the 3′-UTR. One example is Zwint. In contrast to the constitutively expressed variant, the induced Zwint transcript harbors multiple regulatory elements in the 3′-UTR. Taken together, our study provides a comprehensive analysis of the transcriptomic response to neuronal activity and sheds new light on expression kinetics and alternative splicing events.

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