title: 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.
authors.affiliation: Institute for Molecular and Cellular Cognition, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Hermey
authors.forename: Claudia
authors.initials: C
authors.lastname: Mahlke
authors.forename: Jakob J
authors.initials: JJ
authors.lastname: Gutzmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Schreiber
authors.forename: Nils
authors.initials: N
authors.lastname: Blüthgen
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
mesh_terms: D020413:3' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D001665:Binding Sites; D016000:Cluster Analysis; D005091:Exons; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D058977:Molecular Sequence Annotation; D011485:Protein Binding; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D020413:3' Untranslated Regions; D014157:Transcription Factors