title: Mapping Gene Expression in Excitatory Neurons during Hippocampal Late-Phase Long-Term Potentiation.
abstract: The persistence of long-lasting changes in synaptic connectivity that underlie long-term memory require new RNA and protein synthesis. To elucidate the temporal pattern of gene expression that gives rise to long-lasting neuronal plasticity, we analyzed differentially-expressed (DE) RNAs in mouse hippocampal slices following induction of late phase long-term potentiation (L-LTP) specifically within pyramidal excitatory neurons using Translating Ribosome Affinity Purification RNA sequencing (TRAP-seq). We detected time-dependent changes in up- and down-regulated ribosome-associated mRNAs over 2 h following L-LTP induction, with minimal overlap of DE transcripts between time points. TRAP-seq revealed greater numbers of DE transcripts and magnitudes of LTP-induced changes than RNA-seq of all cell types in the hippocampus. Neuron-enriched transcripts had greater changes at the ribosome-loading level than the total RNA level, while RNA-seq identified many non-neuronal DE mRNAs. Our results highlight the importance of considering both time course and cell-type specificity in activity-dependent gene expression during memory formation.
authors.affiliation: Interdepartmental Program in Neurosciences, University of California, Los Angeles Los Angeles, CA, USA.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Chen
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles Los Angeles, CA, USA.
authors.forename: Riki
authors.initials: R
authors.lastname: Kawaguchi
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles Los Angeles, CA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Blum
authors.affiliation: Department of Biological Chemistry, University of California, Los Angeles Los Angeles, CA, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Achiro
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles Los Angeles, CA, USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.affiliation: Department of Physiology, University of California, Los Angeles Los Angeles, CA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: O'Dell
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los AngelesLos Angeles, CA, USA; Department of Biological Chemistry, University of California, Los AngelesLos Angeles, CA, USA.
authors.forename: Kelsey C
authors.initials: KC
authors.lastname: Martin
keywords: RNA sequencing; gene profiling; hippocampus; long-term potentiation; synaptic plasticity; translational regulation