Mapping Gene Expression in Excitatory Neurons during Hippocampal Late-Phase Long-Term Potentiation

Patrick B Chen; Riki Kawaguchi; Charles Blum; Jennifer M Achiro; Giovanni Coppola; Thomas J O'Dell; Kelsey C Martin

doi:10.3389/fnmol.2017.00039

Mapping Gene Expression in Excitatory Neurons during Hippocampal Late-Phase Long-Term Potentiation

Front Mol Neurosci. 2017 Feb 22:10:39. doi: 10.3389/fnmol.2017.00039. eCollection 2017.

Authors

Patrick B Chen¹, Riki Kawaguchi², Charles Blum², Jennifer M Achiro³, Giovanni Coppola², Thomas J O'Dell⁴, Kelsey C Martin⁵

Affiliations

¹ Interdepartmental Program in Neurosciences, University of California, Los Angeles Los Angeles, CA, USA.
² Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles Los Angeles, CA, USA.
³ Department of Biological Chemistry, University of California, Los Angeles Los Angeles, CA, USA.
⁴ Department of Physiology, University of California, Los Angeles Los Angeles, CA, USA.
⁵ 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.

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.

Keywords: RNA sequencing; gene profiling; hippocampus; long-term potentiation; synaptic plasticity; translational regulation.

Abstract

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