Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA316996 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR3317240.fastq.gz | Fastqsanger.gz | |||
| SRR3317250_1.fastq.gz | Fastqsanger.gz | |||
| SRR3317250_2.fastq.gz | Fastqsanger.gz | |||
| SRR3317260_1.fastq.gz | Fastqsanger.gz | |||
| SRR3317260_2.fastq.gz | Fastqsanger.gz |
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Project description:The long-lasting changes in synaptic connectivity that underlie long-term memory require new RNA and protein synthesis for their persistence. To elucidate the temporal pattern of gene expression that gives rise to long-lasting, learning-related neuronal plasticity, we profiled RNAs in mouse hippocampal CA3-CA1 slices following induction of late phase long-term potentiation (LTP), analyzing differential expression (DE) specifically within pyramidal excitatory neurons by Translating Ribosome Affinity Purification RNA sequencing (TRAP-seq). We detected time-dependent changes in up- and down-regulated ribosome-associated mRNAs over the two hours following LTP induction, with minimal overlap of DE transcripts between time points. TRAP-seq revealed greater numbers and amplitudes of LTP-induced changes than RNA-seq of all cell types in the hippocampus. Transcripts that were DE by TRAP-seq but not RNA-seq were enriched in mRNAs encoding cytoskeletal and cell adhesion proteins, while RNA-seq identified DE in many non-neuronal mRNAs. Together our results highlight the importance of considering both the time course and the cell-type specificity of activity-dependent gene expression during memory formation.
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Project description:Expression of VP16-CREB, a constitutively active form of CREB, in hippocampal neurons of the CA1 region lowers the threshold for eliciting the late, persistent phase of long-term potentiation (L-LTP) in the Schaffer collateral pathway. This VP16-CREB-mediated L-LTP differs from the conventional late phase of LTP in not being dependent on new transcription. This finding suggests that in the transgenic mice the mRNA transcript(s) encoding the protein(s) necessary for this form of L-LTP might already be present in CA1 neurons in the basal condition. We used high-density oligonucleotide arrays to identify the mRNAs differentially expressed in the hippocampus of transgenic and wild-type mice. Experiment Overall Design: To identify the specific gene whose induction in hippocampal neurons correlated with the facilitated L-LTP phenotype, we harvested hippocampal mRNA at time points assessed in our physiological study and carried out a gene expression analysis using oligonucleotide microarrays. To obtain a sufficient quantity of poly(A)-RNA and reduce the effect of the biological variability of the sample, hippocampi from 6 to 10 mice matched for genotype and time of induction were pooled together in each sample. The final data set included genechips for animals on dox (gene Off) and for animals that were one, two, and five weeks after removal of dox (gene On). We also included samples from wild-type mice maintained under identical conditions and from transgenic mice that expressed VP16-CREB for three weeks before turning the transgene off again for two weeks with dox (Rev, gene Off). Since the isolation of mRNA from the whole hippocampus favors genes that are more broadly over-expressed in the hippocampus of transgenic mice and, therefore, may lead to an underestimation of the total complement of genes showing an altered expression in specific hippocampal subregions, we extended our comparison between transgenic and wild-type expression profiles using microdissected CA1 regions. We obtained two samples corresponding to VP16-CREB mice three weeks after induction and one sample corresponding to wild-type mice kept in the same conditions. Experiment Overall Design: These twelve mRNA samples were analyzed using Affymetrix genechips MG-U74v2 setA.
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