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.
Highlights
Synaptic plasticity, the experience-dependent remodeling of neuronal connectivity, provides a means of storing memories in the brain (Milner et al, 1998)
Previous studies have shown that pharmacological inhibition of transcription and translation within an early time window (∼2 h) has no effect on the persistence of late phase of LTP (L-LTP) (Nguyen et al, 1994; Fonseca et al, 2006; Alberini, 2008, 2009)
The RiboTag mouse expresses floxed HA-tagged ribosomal protein L22 (HAL22) in cells expressing Cre recombinase, which allows for immunoprecipitation of ribosome-associated transcripts in a cell-type specific manner (Sanz et al, 2009)
Summary
The experience-dependent remodeling of neuronal connectivity, provides a means of storing memories in the brain (Milner et al, 1998). Previous studies have shown that pharmacological inhibition of transcription and translation within an early time window (∼2 h) has no effect on the persistence of L-LTP (Nguyen et al, 1994; Fonseca et al, 2006; Alberini, 2008, 2009) These observations are consistent with the idea that a critical early temporal window of new transcription and translation underlies the persistence of stimulus-induced plasticity and memory (Huang et al, 1996). We profiled the temporal pattern of gene expression within excitatory pyramidal neurons following induction of Schaffer collateral (CA3 to CA1) hippocampal LTP
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
