Similar Datasets
Project description:Subiculum pyramidal cells constitute a prominent output neuron class of the hippocampus. Here, we examined diversity in this cell type using single-cell RNA-seq.
2018-10-29 | GSE113069 | GEO
Project description:Considerable work emphasizes a role for hippocampal circuits in governing contextual fear discrimination. However, the intra- and extrahippocampal pathways that route contextual information to cortical and subcortical circuits to guide adaptive behavioral responses are poorly understood. Using terminal-specific optogenetic silencing in a contextual fear discrimination learning paradigm, we identify opposing roles for dorsal CA3-CA1 (dCA3-dCA1) projections and dorsal CA3-dorsolateral septum (dCA3-DLS) projections in calibrating fear responses to certain and ambiguous contextual threats, respectively. Ventral CA3-DLS (vCA3-DLS) projections suppress fear responses in both certain and ambiguous contexts, whereas ventral CA3-CA1 (vCA3-vCA1) projections promote fear responses in both these contexts. Lastly, using retrograde monosynaptic tracing, ex vivo electrophysiological recordings, and optogenetics, we identify a sparse population of DLS parvalbumin (PV) neurons as putative relays of dCA3-DLS projections to diverse subcortical circuits. Taken together, these studies illuminate how distinct dCA3 and vCA3 outputs calibrate contextual fear discrimination.
| S-EPMC7050277 | biostudies-literature
Project description:The subiculum is a patchwork of discrete subregions
| PRJNA449925 | ENA
Project description:The transcriptional repressor Zbtb20 is essential for specification of hippocampal CA1 pyramidal neurons. Moreover, ectopic expression of Zbtb20 is sufficient to transform subicular and retrosplenial areas of D6/Zbtb20S mice to CA1. We used microarrays to identify genes that are repressed by Zbtb20 in developing CA1 pyramidal neurons in the CA1-transformed cortex of D6/Zbtb20S mice. For RNA extraction and hybridization on Affymetrix microarrays, we isolated the CA1-transformed subiculum and retrosplenial cortex from postnatal day 1 D6/Zbtb20S mice, as well as corresponding areas from their wildtype littermates. Total RNA was extracted using the RNeasy Lipid Tissue Mini Kit (Qiagen). Each RNA sample represents a pool of RNA obtained from dissected tissues of seven animals.
2014-04-11 | E-GEOD-38837 | biostudies-arrayexpress
Project description:People with Down syndrome (DS) have intellectual disability (ID) and develop hallmark Alzheimer’s disease (AD) pathology during midlife. There are several circuits underlying memory and executive function in the DS and AD brain that are particularly vulnerable and degenerate early in disease, most notably the septohippocampal circuit and the trisynaptic loop in the hippocampus. A fundamental lack of knowledge exists as to the etiology and mechanisms of disease progression within these critical circuits vulnerable to degeneration in DS, AD, and relevant models. This is compounded by new evidence that suggests spatial localization of neurons has profound effects on activity and innervation within the hippocampal CA1 region. We postulated gene expression changes in a DS mouse model, at a time that these circuits of input to the CA1 are degraded, would have a significant effect on gene expression in CA1 pyramidal neurons. Further, this dysfunction may be specific to spatial localization and innervation. Laser capture microscopy on pyramidal neurons from CA1 was performed, isolating the entire CA1 pyramidal neuron layer, which was compared to select populations of deep and superficial pyramidal neurons from CA1a (distal CA1, adjacent to the subiculum). RNA-seq and bioinformatic analysis was performed where profound differences in dysregulation in the DS mouse model based on their spatial location and postulated circuitry were examined.
2024-08-26 | GSE264258 | GEO
Project description:Purpose: This study aims to characterize gene expression changes in dorsal and ventral subiculum after the induction of acute seizures by electrical stimulation of the Perforant Pathway (PP) in rats. Methodolody: The dorsal (dSub) and ventral (vSub) subiculum regions were collected by laser- microdissection laser 24 hours after preconditioning protocol, RNA was extracted using Trizol, RNA sequencing was performed in a Hiseq 4000 platform. Reads were aligned to the Rattus norvegicus Ensembl Rnor 5.0 assemble genome using the STAR, DESEq2 statistics package was used to estimate gene expression and for statistical analysis. Results: We identified a total of 1176 differentially expressed genes, in which 204 genes were differentially expressed in dSub and 972 differential expression genes in vSub comparing control to preconditioning samples. The gene ontology enrichment analysis showed that the most significant common enrichment pathway considering up-regulated genes in dSub and vSub was Cholesterol Biosynthesis, while the most significant enrichment pathway considering down-regulated genes in vSub was Axon guidance. Moreover, we found GFAP, C3 and GAD2 up-regulated in dSub and vSub, downregulation of GLS2 in dSub and vSub, and downregulation of GAT-1 in vSub. Conclusion: These findings suggest preconditioning by PP electrical stimulations might induce synaptic reorganization, complement system activation, decreased glutamatergic transmission, and increased GABA transmission in subiculum areas. In the ventral subiculum, the down-regulation of proapoptotic genes and axon guidance indicates that preconditioning induces a neuroprotective environment in this region.
2021-06-18 | GSE178409 | GEO
Project description:The tumour suppressor PTEN (phosphatase and tensin deleted on chromosome 10) regulates major cellular functions via lipid phosphatase-dependent and -independent mechanisms. Despite its fundamental pathophysiological importance, how PTEN's cellular activity is regulated has only been partially elucidated. We report that the scaffolding proteins ?-arrestins (?-arrs) are important regulators of PTEN. Downstream of receptor-activated RhoA/ROCK signalling, ?-arrs activate the lipid phosphatase activity of PTEN to negatively regulate Akt and cell proliferation. In contrast, following wound-induced RhoA activation, ?-arrs inhibit the lipid phosphatase-independent anti-migratory effects of PTEN. ?-arrs can thus differentially control distinct functional outputs of PTEN important for cell proliferation and migration.
| S-EPMC3155309 | biostudies-literature
Project description:Successfully navigating in physical or semantic space requires a neural representation of allocentric (map-based) vectors to boundaries, objects and goals. Cognitive processes such as path-planning and imagination entail the recall of vector representations, but evidence of neuron-level memory for allocentric vectors has been lacking. Here, we describe a novel neuron type, vector trace cell (VTC), whose firing generates a new vector field when a cue is encountered and a 'trace' version of that field for hours after cue removal. VTCs are concentrated in subiculum, distal to CA1. Compared to non-trace cells, VTCs fire at further distances from cues and exhibit earlier-going shifts in preferred theta phase in response to newly introduced cues, which demonstrates a theta-linked neural substrate for memory encoding. VTCs suggest a vector-based model of computing spatial relationships between an agent and multiple spatial objects, or between different objects, freed from the constraints of direct perception of those objects.
| S-EPMC7116739 | biostudies-literature
Project description:AbtractForkhead box A1 (FOXA1) is a pioneer transcription factor that is essential for the normal development of several endoderm-derived organs, including the prostate gland1,2. FOXA1 is frequently mutated in hormone-receptor-driven prostate, breast, bladder and salivary-gland tumours3-8. However, it is unclear how FOXA1 alterations affect the development of cancer, and FOXA1 has previously been ascribed both tumour-suppressive9-11 and oncogenic12-14 roles. Here we assemble an aggregate cohort of 1,546 prostate cancers and show that FOXA1 alterations fall into three structural classes that diverge in clinical incidence and genetic co-alteration profiles, with a collective prevalence of 35%. Class-1 activating mutations originate in early prostate cancer without alterations in ETS or SPOP, selectively recur within the wing-2 region of the DNA-binding forkhead domain, enable enhanced chromatin mobility and binding frequency, and strongly transactivate a luminal androgen-receptor program of prostate oncogenesis. By contrast, class-2 activating mutations are acquired in metastatic prostate cancers, truncate the C-terminal domain of FOXA1, enable dominant chromatin binding by increasing DNA affinity and-through TLE3 inactivation-promote metastasis driven by the WNT pathway. Finally, class-3 genomic rearrangements are enriched in metastatic prostate cancers, consist of duplications and translocations within the FOXA1 locus, and structurally reposition a conserved regulatory element-herein denoted FOXA1 mastermind (FOXMIND)-to drive overexpression of FOXA1 or other oncogenes. Our study reaffirms the central role of FOXA1 in mediating oncogenesis driven by the androgen receptor, and provides mechanistic insights into how the classes of FOXA1 alteration promote the initiation and/or metastatic progression of prostate cancer. These results have direct implications for understanding the pathobiology of other hormone-receptor-driven cancers and rationalize the co-targeting of FOXA1 activity in therapeutic strategies.
| S-EPMC6661908 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-12-12 | GSE123625 | GEO