Similar Datasets
Project description:RNA localization is one mechanism neurons use to spatially and temporally regulate gene expression at synapses. Here, we test the hypothesis that cells exhibiting distinct forms of synaptic plasticity will have differences in dendritically localized RNAs. Indeed, we discover that each major subregion of the adult mouse hippocampus expresses a unique complement of dendritic RNAs. Specifically, we describe more than 1,000 differentially expressed dendritic RNAs, suggesting that RNA localization and local translation are regulated in a cell type-specific manner. Furthermore, by focusing Gene Ontology analyses on the plasticity-resistant CA2, we identify an enrichment of mitochondria-associated pathways in CA2 cell bodies and dendrites, and we provide functional evidence that these pathways differentially influence plasticity and mitochondrial respiration in CA2. These data indicate that differences in dendritic transcriptomes may regulate cell type-specific properties important for learning and memory and may influence region-specific differences in disease pathology.
| S-EPMC6894405 | biostudies-literature
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
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 | GSE116342 | GEO
Project description:Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2
| PRJNA478214 | ENA
Project description:Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2 [array]
| PRJNA478218 | ENA
Project description:Hippocampal Subregions Express Distinct Dendritic Transcriptomes that Reveal Differences in Mitochondrial Function in CA2 [RNA-seq]
| PRJNA478217 | ENA
Project description:Cortical neurons activated during recent experiences often reactivate with dorsal hippocampal CA1 sharp-wave ripples (SWRs) during subsequent rest. Less is known about cortical interactions with intermediate hippocampal CA1, whose connectivity, functions, and SWRs differ from those of dorsal CA1. We identified three clusters of visual cortical excitatory neurons that are excited together with either dorsal or intermediate CA1 SWRs, or suppressed before both SWRs. Neurons in each cluster were distributed across primary and higher visual cortices and co-active even in the absence of SWRs. These ensembles exhibited similar visual responses but different coupling to thalamus and pupil-indexed arousal. We observed a consistent activity sequence: (i) suppression of SWR-suppressed cortical neurons, (ii) thalamic silence, and (iii) activation of the cortical ensemble preceding and predicting intermediate CA1 SWRs. We propose that the coordinated dynamics of these ensembles relay visual experiences to distinct hippocampal subregions for incorporation into different cognitive maps.
| S-EPMC10055189 | biostudies-literature
Project description:Impairment of hippocampal-dependent spatial learning and memory with aging affects a large segment of the aged population. Hippocampal subregions (CA1, CA3, and DG) have been previously reported to express both common and specific morphological, functional, and gene/protein alterations with aging and cognitive decline. To comprehensively assess gene expression with aging and cognitive decline, transcriptomic analysis of CA1, CA3, and DG was conducted using Adult (12M) and Aged (26M) F344xBN rats behaviorally characterized by Morris water maze performance. Each subregion demonstrated a specific pattern of responses with aging and with cognitive performance. The CA1 and CA3 demonstrating the greatest degree of shared gene expression changes. Analysis of the pathways, processes, and regulators of these transcriptomic changes also exhibit a similar pattern of commonalities and differences across subregions. Gene expression changes between Aged cognitively Intact and Aged cognitively Impaired rats often showed an inversion of the changes between Adult and Aged rats. This failure to adapt rather than an exacerbation of the aging phenotype questions a conventional view that cognitive decline is exaggerated aging. These results are a resource for investigators studying cognitive decline and also demonstrate the need to individually examine hippocampal subregions in molecular analyses of aging and cognitive decline.
| S-EPMC4271093 | biostudies-literature
Project description:Introduction:Converging evidence suggests that hippocampal subregions subserve different functions, and are differentially affected by psychosis illness progression. Despite this fact, studies have not often studied subregions cross-sectionally across the psychosis spectrum. Furthermore, little is known about associations between subregion volumes and hippocampus-mediated cognition. Methods:A total of 222 participants (61 ultra high risk [UHR], 91 schizophrenia [SCZ], and 70 healthy volunteers) underwent a 3T MRI scan, as well as structured clinical interviews and a cognitive battery. Hippocampal subfield analysis was conducted with Freesurfer. We compared subregion volumes across groups, controlling for age, gender, and intracranial volume. We also examined associations in the UHR and SCZ groups between hippocampal subregion volumes and verbal learning, visual learning, and working memory. Results:We found a dose-dependent relationship such that the SCZ group showed significantly greater subfield volume reductions than the UHR group, which in turn showed significantly greater subfield volume reductions than the healthy volunteer group. We also found associations between subregion volume and cognitive performance in the visual memory, verbal memory, and working memory domains. Discussion:Our study examined hippocampal subregion volumes cross-sectionally in a large sample across the psychosis spectrum, as well as links with hippocampus-mediated cognitive function. Our findings suggest that hippocampal abnormalities emerge before first psychosis episode onset, and may be etiologically informative.
| S-EPMC6101630 | biostudies-literature
Project description:The formation and recall of episodic memory requires precise information processing by the entorhinal-hippocampal network. For several decades, the trisynaptic circuit entorhinal cortex layer II (ECII)→dentate gyrus→CA3→CA1 and the monosynaptic circuit ECIII→CA1 have been considered the primary substrates of the network responsible for learning and memory. Circuits linked to another hippocampal region, CA2, have only recently come to light. Using highly cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings, we found that dentate gyrus cells, long believed to not project to CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic circuit, but, unlike CA3, projected preferentially to the deep, rather than to the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge, ECIII did not project to CA2. Our results allow a deeper understanding of the biology of learning and memory.
| S-EPMC4004172 | biostudies-literature