Hipposeq: an RNA-seq based atlas of gene expression in excitatory hippocampal neurons
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE74985 | GEO | 2016/04/22
SECONDARY ACCESSION(S): PRJNA302123
REPOSITORIES: GEO
Similar Datasets
Project description:Neurodegenerative brain disorders become more common in the aged. Most of these disorders are associated with or caused by selective death of certain neuronal subpopulations. The mechanisms underlying the differential vulnerability of certain neuronal populations are still largely unexplored and few neuroprotective treatments are available to date. Elucidation of these mechanisms may lead to a greater understanding of the pathogenesis and treatment of neurodegenerative diseases. Moreover, preconditioning by a short seizure confers neuroprotection following a subsequent prolonged seizure. Our goal is to identify pathways that confer vulnerability and resistance to neurotoxic conditions by comparing the basal and preconditioned gene expression profiles of three differentially vulnerable hippocampal neuron populations. Hippocampal CA1 and CA3 pyramidal neurons are highly susceptible to seizures and ischemia, whereas dentate gyrus granule cells are relatively resistant. A brief preconditioning seizure confers protection to the pyramidal cells. We will first determine gene expression profiles of untreated rat CA1 and CA3 pyramidal cells, and dentate granule cells, using laser capture microscopy to obtain region-specific neuronal mRNA. We will then determine the effect of a brief preconditioning seizure, which is neuroprotective in CA1 and CA3, on these expression profiles. We hypothesize that common molecular mechanisms exist in neurons that determine their susceptibility to seizure-induced injury. Intrinsic differences in gene expression exist between hippocampal glutamatergic CA1 and CA3 pyramidal neurons, on the one hand, and dentate granule cells on the other, which contribute to the greater susceptibility of pyramidal neurons to degeneration in experimental stroke and epilepsy. We specifically hypothesize that differences in basal energy metabolism genes may confer differential susceptibility to neurodegeneration produced by seizures and ischemia. Anesthetized animals will be sacrificed by decapitation, and frozen 10 micron sections will be lightly stained with cresyl violet to identify cell layers in the hippocampus. Approximately 1000 neurons from each of the three cell layers will be isolated by LCM. Poly-A RNA will be amplified using a modified Eberwine protocol. The quality of our aRNA will be evaluated by quantitative RT-PCR of GluR6 and KA2 mRNA levels before we send the samples to the Center for labeling and hybridization to Affymetrix rat 230A arrays. We will provide a one-round amplification cDNA product to the center for labeling and hybridization. This protocol is identical to a previously approved study by Jim Greene in our laboratory.
2007-09-18 | E-GEOD-1994 | biostudies-arrayexpress
Project description:Neurological diseases can lead to the denervation of brain regions caused by demyelination, traumatic injury or cell death. Nevertheless, the molecular and structural mechanisms underlying lesion-induced reorganization of denervated brain regions are a matter of ongoing investigation. In order to address this issue, we performed an entorhinal cortex lesion (ECL) in mouse organotypic entorhino-hippocampal tissue cultures of both sexes and studied denervation-induced plasticity of mossy fiber synapses, which connect dentate granule cells (dGCs) with CA3 pyramidal cells (CA3-PCs) and play important roles in spatial learning. Partial denervation caused a strengthening of excitatory neurotransmission in dGCs, in CA3-PCs, and their direct synaptic connections as revealed by paired recordings (GC-to-CA3). These functional changes were accompanied by ultrastructural reorganization of mossy fiber synapses, which regularly contain the plasticity-related protein synaptopodin and the spine apparatus organelle. We demonstrate that the spine apparatus organelle and its integral protein synaptopodin are associated with ribosomes in close proximity to synaptic sites and unravel a synaptopodin-related transcriptome. Notably, synaptopodin-deficient tissue preparations that lack the spine apparatus organelle, failed to express lesion-induced synaptic adjustments. Hence, synaptopodin and the spine apparatus organelle play a crucial role in regulating lesion-induced synaptic plasticity at hippocampal mossy fiber synapses.
2022-10-28 | GSE216509 | GEO
Project description:Neurodegenerative brain disorders become more common in the aged. Most of these disorders are associated with or caused by selective death of certain neuronal subpopulations. The mechanisms underlying the differential vulnerability of certain neuronal populations are still largely unexplored and few neuroprotective treatments are available to date. Elucidation of these mechanisms may lead to a greater understanding of the pathogenesis and treatment of neurodegenerative diseases. Moreover, preconditioning by a short seizure confers neuroprotection following a subsequent prolonged seizure. Our goal is to identify pathways that confer vulnerability and resistance to neurotoxic conditions by comparing the basal and preconditioned gene expression profiles of three differentially vulnerable hippocampal neuron populations. Hippocampal CA1 and CA3 pyramidal neurons are highly susceptible to seizures and ischemia, whereas dentate gyrus granule cells are relatively resistant. A brief preconditioning seizure confers protection to the pyramidal cells. We will first determine gene expression profiles of untreated rat CA1 and CA3 pyramidal cells, and dentate granule cells, using laser capture microscopy to obtain region-specific neuronal mRNA. We will then determine the effect of a brief preconditioning seizure, which is neuroprotective in CA1 and CA3, on these expression profiles. We hypothesize that common molecular mechanisms exist in neurons that determine their susceptibility to seizure-induced injury. Intrinsic differences in gene expression exist between hippocampal glutamatergic CA1 and CA3 pyramidal neurons, on the one hand, and dentate granule cells on the other, which contribute to the greater susceptibility of pyramidal neurons to degeneration in experimental stroke and epilepsy. We specifically hypothesize that differences in basal energy metabolism genes may confer differential susceptibility to neurodegeneration produced by seizures and ischemia. Anesthetized animals will be sacrificed by decapitation, and frozen 10 micron sections will be lightly stained with cresyl violet to identify cell layers in the hippocampus. Approximately 1000 neurons from each of the three cell layers will be isolated by LCM. Poly-A RNA will be amplified using a modified Eberwine protocol. The quality of our aRNA will be evaluated by quantitative RT-PCR of GluR6 and KA2 mRNA levels before we send the samples to the Center for labeling and hybridization to Affymetrix rat 230A arrays. We will provide a one-round amplification cDNA product to the center for labeling and hybridization. This protocol is identical to a previously approved study by Jim Greene in our laboratory. Keywords: other
2004-11-24 | GSE1994 | GEO
Project description:Microarrays were used to assess the gene expression patterns in the CA1, CA3, and dentate gyrus of the rTg4510 mouse line at 4.5 months of age. This line harbors a repressible mutant human Tau transgene under the Camk2a promoter. Both mice with just the tet-Transactivator alone and no transgenes ('double negative') were used as comparison groups. Cellular layers of the CA1, CA3, and dentate gyrus (DG) from 5 or 6 mice per genotype at ages 4.5 months were laser capture dissected, RNA was isolated, and hybridization to Affymetrix microarrays performed.
2014-06-14 | E-GEOD-57528 | biostudies-arrayexpress
Project description:Microarrays were used to assess the gene expression patterns in the CA1, CA3, and dentate gyrus of the rTg4510 mouse line at 6.1 months of age. This line harbors a repressible mutant human Tau transgene under the Camk2a promoter. Both mice with just the tet-Transactivator alone and no transgenes ('double negative') were used as comparison groups. Cellular layers of the CA1, CA3, and dentate gyrus (DG) from 5 or 6 mice per genotype at age 6.1 months were laser capture dissected, RNA was isolated, and hybridization to Affymetrix microarrays performed.
2014-06-14 | E-GEOD-57583 | biostudies-arrayexpress
Project description:Complete global brain ischemia (CGBI) and reperfusion occur following resuscitation from cardiac arrest. Different brain neurons are selectively vulnerable to CGBI: pyramidal neurons of hippocampal CA3 survive 10 min CGBI but those of CA1 die at 3 days following 10 min CGBI. CA3 neurons are expected to have more robust stress responses and repair responses than CA1 neurons. We used microarrays to compared total and polysome-bound mRNAs in CA1 and CA3 at 8 hr reperfusion after 10 min CGBI in Long Evans male rats to ascertain differences in total vs polysome-bound gene expression.
2016-06-02 | GSE82146 | GEO
Project description:Complete global brain ischemia (CGBI) and reperfusion occur following resuscitation from cardiac arrest. Different brain neurons are selectively vulnerable to CGBI: pyramidal neurons of hippocampal CA3 survive 10 min CGBI but those of CA1 die at 3 days following 10 min CGBI. CA3 neurons are expected to have more robust stress responses and repair responses than CA1 neurons. We used microarrays to compared total and polysome-bound mRNAs in CA1 and CA3 at 8 hr reperfusion after 10 min CGBI in Long Evans male rats to ascertain differences in total vs polysome-bound gene expression. Male Long Evans rats were subjected to (1) sham operation (non-ischemic control, NIC) or normothermic CGBI of 10 min followed by 8 hr reperfusion (8R). Hippocampal CA1 and CA3 were dissected. n = 5 CA1 or CA3 were pooled to give a single replicate and there were 3 or 4 replicates per group. Post-mitochondrial supernatant (PMS) was prepared. Twenty percent of PMS was TRIzol extracted to give total RNA. The remainder was run on a 20% sucrose pad to isolate polysome pellets, which were also TRIzol extracted to give polysome RNA. Total and polysome RNA were then run on Affymetrix Rat Gene 2.0 microarrays.
2016-06-02 | E-GEOD-82146 | biostudies-arrayexpress
Project description:Tissue and organ function has been conventionally understood in terms of the interactions among discrete and homogeneous cell types. This approach has proven difficult in neuroscience due to the marked diversity across different neuron classes, but may also be further hampered by prominent within-class variability. Here, we considered a well-defined, canonical neuronal population â hippocampal CA1 pyramidal cells â and systematically examined the extent and spatial rules of transcriptional heterogeneity. Using next-generation RNA sequencing, we identified striking variability in CA1 PCs, such that the differences along the dorsal-ventral axis rivaled differences across distinct pyramidal neuron classes. This variability emerged from a spectrum of continuous expression gradients, producing a profile consistent with a multifarious continuum of cells. This work reveals an unexpected amount of variability within a canonical and narrowly defined neuronal population and suggests that continuous, within-class heterogeneity may be an important feature of neural circuits. Hippocampal RNA profiles were generated by deep sequencing on Illumina HiSeq 2500, with three biological replicates per population
2016-01-05 | E-GEOD-67403 | biostudies-arrayexpress
Project description:The medial pallium (MP) is the major forebrain region underlying learning and memory, spatial navigation, and emotion; however, the mechanisms underlying the specification of its principal neuron subtypes remain largely unexplored. Here, by postmitotic deletion of FOXG1 (a transcription factor linked to autism and FOXG1 syndrome) and single-cell RNA sequencing, we found that FOXG1 controls the specification of upper-layer retrosplenial cortical pyramidal neurons (RSC-PyNs (UL)), subiculum PyNs (SubC-PyNs), CA1-PyNs, CA3-PyNs and dentate gyrus granule cells (DG-GCs) in the mouse MP. We uncovered subtype-specific and subtype-shared FOXG1-regulated transcriptomic networks orchestrating MP neuron specification.
2022-10-19 | GSE215356 | GEO
Project description:We report here the bacTRAP (bacterial artificial chromosome , translating ribosome affinity purification) profiling of 7 different types of neurons in the mouse, at three different ages: two neuron types very vulnerable to AD (principal cells of entorhinal cortex layer II - ECII), pyramidal cells of hippocampus CA1, and 5 types of neurons more resistant to AD (pyramidal cells of hippocampus CA2 and CA3, granule neurons of the dentate gyrus, pyramidal cells from layer IV of primary visual cortex V1, and pyramidal cells from layer II/III and V of primary somatosensory cortex S1). Using these profiles we generated molecular signatures for each of these cell types, proved that the molecular identity of these cell types is very well conserved across mouse and humans, and constructed functional networks for each cell type that allowed us to identify genes and pathways associated with selective neuronal vulnerability in AD. We also report the profiling of ECII neurons in APP/PS1 mice (a mouse model of Abeta accumulation) at 6 months of age.
2020-05-30 | GSE151460 | GEO