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Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2 [RNA-seq]

ABSTRACT: RNA localization is one mechanism that neurons use to spatially and temporally regulate gene expression at synapses. Here, we tested the hypothesis that cells exhibiting distinct forms of synaptic plasticity will have differences in dendritically localized RNAs. Indeed, we discovered that each major subregion of the adult mouse hippocampus expresses a unique complement of dendritic RNAs. Specifically, we uncovered a surprising number of cell type and compartment specific differences in RNA expression and alternative splicing, some of which pointed to differences within interneuron and non-neuronal cells present in dendritic laminae. Further, by focusing gene-ontology analyses on the plasticity-resistant CA2, we identified an enrichment of mitochondria-associated pathways in CA2 cell bodies and dendrites, and we provide functional evidence that these pathways influence plasticity and mitochondrial respiration in CA2. In sum, our results support accumulating evidence that thousands of RNAs are present in adult dendrites that likely function to regulate cell type specific processes in dendrites.

ORGANISM(S): Mus musculus

PROVIDER: GSE116342 | GEO | 2019/09/23

REPOSITORIES: GEO

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Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2 [array]

Project description:RNA localization is one mechanism that neurons use to spatially and temporally regulate gene expression at synapses. Here, we tested the hypothesis that cells exhibiting distinct forms of synaptic plasticity will have differences in dendritically localized RNAs. Indeed, we discovered that each major subregion of the adult mouse hippocampus expresses a unique complement of dendritic RNAs. Specifically, we uncovered a surprising number of cell type and compartment specific differences in RNA expression and alternative splicing, some of which pointed to differences within interneuron and non-neuronal cells present in dendritic laminae. Further, by focusing gene-ontology analyses on the plasticity-resistant CA2, we identified an enrichment of mitochondria-associated pathways in CA2 cell bodies and dendrites, and we provide functional evidence that these pathways influence plasticity and mitochondrial respiration in CA2. In sum, our results support accumulating evidence that thousands of RNAs are present in adult dendrites that likely function to regulate cell type specific processes in dendrites.

2019-09-23 | GSE116328 | GEO

Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2

Project description:Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2

| PRJNA478214 | ENA

Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2 [array]

Project description:Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2 [array]

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Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2 [RNA-seq]

Project description:Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2 [RNA-seq]

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Functionally diverse dendritic mRNAs rapidly associate with ribosomes following a novel experience

Project description:The subcellular localization and translation of messenger RNA (mRNA) supports functional differentiation between cellular compartments. In neuronal dendrites, local translation of mRNA provides a rapid and specific mechanism for synaptic plasticity and memory formation, and might be involved in the pathophysiology of certain brain disorders. Despite the importance of dendritic mRNA translation, little is known about which mRNAs can be translated in dendrites in vivo and when their translation occurs. Here we collect ribosome-bound mRNA from the dendrites of CA1 pyramidal neurons in the adult mouse hippocampus. We find that dendritic mRNA rapidly associates with ribosomes following a novel experience consisting of a contextual fear conditioning trial. High throughput RNA sequencing followed by machine learning classification reveals an unexpected breadth of ribosome-bound dendritic mRNAs, including mRNAs expected to be entirely somatic. Our findings are in agreement with a mechanism of synaptic plasticity that engages the acute local translation of functionally diverse dendritic mRNAs. RNA-Seq of ribosome-bound mRNA immunoprecipitated from dendrites and soma of CA1 pyramidal neurons in the mouse hippocampus

2014-07-30 | E-GEOD-58343 | biostudies-arrayexpress

Total and dendritic ribosome profiling from primary mouse cortical neurons

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Total and dendritic RNA-sequencing from primary mouse cortical neurons

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Functionally diverse dendritic mRNAs rapidly associate with ribosomes following a novel experience

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Microarray analyses that reveal the population of dendritic RNAs and their redistribution by neural activity

Project description:Subcellular localization of RNA is an efficient way to localize proteins to a specific region of a cell. The dendritic localization of RNAs underlies the establishment and maintenance of the synaptic functions of neuronal cells. A requirement for dendritic RNA localization and subsequent local translation has been demonstrated in several forms of experience-dependent synaptic plasticity. In spite of several attempts to identify these RNAs, the population of RNA species present in dendrites as a whole has not been well described. Here we show the results of microarray analyses with RNAs isolated from heavy portion of polysome (HP) fraction where RNA granules are enriched in and synaptosome fraction, prepared from the rat brain. These analyses revealed the complex nature of the dendritic RNA population, which included RNAs that were not expected to be in the dendrites. Neural activity caused by an electroconvulsive shock triggered a redistribution of the population of dendritic transcriptome towards the area of overlap between the HP and the synaptosome, which is assumed to be neck of spine. This redistribution may accompany some changes in the translatability of those transcriptome, which suggests complex mechanisms of local translation in response to synaptic inputs. Keywords: Comparisons of RNAs that are presumed to be derived from neuronal dendritic parts (HP and D4) with those from somas (LP and C2).

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Transcription profiling of rat synaptosomes of the hippocampus vs. total hippocampus reveals activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites

Project description:Mammalian target of rapamycin (mTOR) is implicated in synaptic plasticity and local translation in dendrites. Here we found that the mTOR inhibitor, rapamycin, increased the Kv1.1 voltage-gated potassium channel protein in hippocampal neurons and promoted Kv1.1 surface expression on dendrites without altering its axonal expression. Moreover, endogenous Kv1.1 mRNA was detected in dendrites. Using Kv1.1 fused to the photo-convertible fluorescence protein Kaede as a reporter for local synthesis, we observed Kv1.1 synthesis in dendrites upon inhibition of mTOR or the N-methyl-D-aspartate (NMDA) glutamate receptor. Thus, synaptic excitation may cause local suppression of dendritic Kv1 channels by reducing their local synthesis. Experiment Overall Design: mRNA isoloated from the synaptosomes of the hippocampus is compared to mRNA isolated from the total hippocampus to identify mRNAs that are enriched at the synapse

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