Molecular mechanisms for changing brain connectivity in mice and humans (brain samples)
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PROVIDER: PRJNA1022783 | ENA |
REPOSITORIES: ENA
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Project description:Molecular mechanisms for changing brain connectivity in mice and humans
| PRJNA1022776 | ENA
Project description:Molecular mechanisms for changing brain connectivity in mice and humans (blood samples)
| PRJNA1022780 | ENA
Project description:The goal of this study was to examine commonalities in the molecular basis of learning in mice and humans. In our previous work on mouse learning we suppressed activity in the anterior cingulate cortex (ACC) and hippocampus (HC) and found the stages for which each area was critical in performing a 2-choice visuospatial discrimination task. Our current study began by examining gene expression changes in mouse ACC and HC as a result of learning a new skill. Genes upregulated in both brain areas were used as candidates to examine commonalities between genes upregulated in mouse and human blood. We used microarrays to identify candidate genes and real-time PCR to compare the mouse results with two forms of human learning. One form involved training in a working memory task (network training), the other a generalized training shown to change many networks (meditation). We identified two genes that were upregulated in both mice and humans following training. We believe these genes act to regulate pathways that influence NF-κB, a factor previously found to be related to enhanced synaptic function and learning.
2023-10-31 | GSE244393 | GEO
Project description:The goal of this study was to examine commonalities in the molecular basis of learning in mice and humans. In our previous work on mouse learning we suppressed activity in the anterior cingulate cortex (ACC) and hippocampus (HC) and found the stages for which each area was critical in performing a 2-choice visuospatial discrimination task. Our current study began by examining gene expression changes in mouse ACC and HC as a result of learning a new skill. Genes upregulated in both brain areas were used as candidates to examine commonalities between genes upregulated in mouse and human blood. We used microarrays to identify candidate genes and real-time PCR to compare the mouse results with two forms of human learning. One form involved training in a working memory task (network training), the other a generalized training shown to change many networks (meditation). We identified two genes that were upregulated in both mice and humans following training. We believe these genes act to regulate pathways that influence NF-κB, a factor previously found to be related to enhanced synaptic function and learning.
2023-10-31 | GSE244394 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-10-31 | GSE244395 | GEO
Project description:The goal of this study was to examine commonalities in the molecular basis of learning in mice and humans. In previous work we have demonstrated that the anterior cingulate cortex (ACC) and hippocampus (HC) are involved in learning a two-choice visuospatial discrimination task. Here, we began by looking for candidate genes upregulated in mouse ACC and HC with learning. We then determined which of these were also upregulated in mouse blood. Finally, we used RT-PCR to compare candidate gene expression in mouse blood with that from humans following one of two forms of learning: a working memory task (network training) or meditation (a generalized training shown to change many networks). Two genes were upregulated in mice following learning: caspase recruitment domain-containing protein 6 (Card6) and inosine monophosphate dehydrogenase 2 (Impdh2). The Impdh2 gene product catalyzes the first committed step of guanine nucleotide synthesis and is tightly linked to cell proliferation. The Card6 gene product positively modulates signal transduction. In humans, Card6 was significantly upregulated, and Impdh2 trended toward upregulation with training. These genes have been shown to regulate pathways that influence nuclear factor kappa B (NF-κB), a factor previously found to be related to enhanced synaptic function and learning.
| S-EPMC10648558 | biostudies-literature
Project description:Connectivity webs mediate the unique biology of mammalian brain. Yet while cell and gene circuit maps are increasing in resolution, knowledge of the molecular interaction networks of the brain is limited. Here, we applied multidimensional biochemical fractionation with precision mass spectrometry to survey endogenous macromolecules in adult mouse brain. We defined a global ‘interactome’ landscape consisting of hundreds of multi-protein complexes, most never reported before. Brain selective assemblies exhibit distinctive biophysical and functional attributes, including enrichment for synaptic, RNA-binding and other evolutionarily conserved proteins showing tissue-, regional- and cell-type specificity. Strikingly, many macromolecules have links to diverse neurological disorders and disease variants, illustrating the broad pathophysiological relevance of the network. We validated a putative 15-member complex associated with Amyotrophic Lateral Sclerosis using reciprocal pulldowns and a transgenic rodent model, establishing balancing functions in alternative splicing and disease progression. This resource facilitates exploration of the mechanistic basis of neuronal function, synaptic plasticity and diseases of the central nervous system.
2020-04-23 | PXD011304 | Pride
Project description:Transplantation is a clinically relevant approach for brain repair, but much remains to be understood about influences of the disease environment in the host on transplant connectivity. To explore the influence of ageing and amyloid pathology in Alzheimer's disease (AD) we examined graft connectivity using monosynaptic Rabies virus tracing in APP/PS1 mice and in 16-18 month-old wild type mice. Neurons differentiated within 4 weeks and integrated well into the host visual cortex receiving input from the regions appropriate for visual cortex. Surprisingly, however, we found a prominent several-fold increase in local visual cortex input connectivity in both amyloid-loaded and aged environment. State-of-the-art deep proteome analysis using mass spectrometry provides first insights into the composition of environments promoting or not local exuberant input connectivity. These data therefore highlight the key role of the host pathology in shaping the input connectome calling for caution in extrapolating from one to another pathological condition.
2022-08-12 | PXD023407 | Pride
Project description:Truncating CHD8 mutations are amongst the highest confidence risk factors for autism spectrum disorders (ASD) identified to date. Here, we report that Chd8 heterozygous mice display increased brain size, motor delay, hypertelorism, pronounced hypoactivity, and anomalous responses to social stimuli. Whereas gene expression in the neocortex is only mildly affected at mid gestation, over 600 genes are differentially expressed in the early postnatal neocortex. Genes involved in cell adhesion and axon guidance are particularly prominent amongst the downregulated transcripts. Resting-state functional MRI identified increased synchronized activity in corticohippocampal and auditory-parietal networks in Chd8 heterozygous mutant mice, implicating altered connectivity as a potential mechanism underlying the behavioral phenotypes. Together, these data suggest that altered brain growth and diminished expression of important neurodevelopmental genes that regulate long-range brain wiring are followed by distinctive anomalies in functional brain connectivity in Chd8 +/− mice. Human imaging studies have reported altered functional connectivity in ASD patients, with long-range under-connectivity seemingly more frequent. Our data suggest that CHD8 haploinsufficiency represents a specific subtype of ASD where neuropsychiatric symptoms are underpinned by long-range over-connectivity.
2018-04-24 | GSE81103 | GEO
Project description:Precise control of gene expression plays fundamental roles in brain development, but the roles of chromatin regulators in neuronal connectivity have remained poorly understood. Here, we find that depletion of the nucleosome remodeling and deacetylation (NuRD) complex in the cerebellar cortex by in vivo RNAi in rats and conditional knockout of the core NuRD subunit Chd4 in mice profoundly impairs the establishment of granule neuron parallel fiber/Purkinje cell synapses. In RNA-Seq analyses of Chd4 conditional knockout mice, we identify a set of nearly 200 genes that are repressed by the NuRD complex in the cerebellum in vivo. Genome-wide ChIP-Seq analyses reveal that the NuRD complex selectively decommissions the promoters of NuRD-repressed genes in the cerebellum in vivo by inducing the deacetylation of histone H3K9/14 and H3K27 and demethylation of H3K4 at these genes. Importantly, temporal control of promoter decommissioning and repression of NuRD target genes upon maturation of the cerebellum requires the NuRD complex. Finally, in a targeted in vivo RNAi screen of NuRD-repressed target genes, we identify the transcription factor Nhlh1, the RNA-binding protein Elavl2, and the presynaptic regulator Cplx3 as negative regulators of presynaptic differentiation in the cerebellar cortex. Together, these findings define NuRD-dependent promoter decommissioning as a developmentally regulated programming mechanism that releases the brake on presynaptic differentiation and thereby drives synaptic connectivity in the mammalian brain. Three distinct histone modifications using postnatal day 6 or day 22 cerebella from wild type (WT) or Chd4 conditional knockout (cKO) mice were examined in duplicate using libraries prepared with the Illumina ChIP-Seq DNA Sample Prep Kit and sequenced on the Illumina HiSeq 2000 platform.
2014-08-18 | E-GEOD-57758 | biostudies-arrayexpress