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Single cell transcriptomic and chromatin profiles suggest Layer Vb is the only layer with shared excitatory cell types in the medial and lateral entorhinal cortex.

ABSTRACT: Single cell transcriptomic and chromatin profiles suggest Layer Vb is the only layer with shared excitatory cell types in the medial and lateral entorhinal cortex.

PROVIDER: PRJEB49098 | ENA |

REPOSITORIES: ENA

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Single cell transcriptomic and chromatin profiles suggest Layer Vb is the only layer with shared excitatory cell types in the medial and lateral entorhinal cortex

Project description:All brain functionality arises from the activity in neural circuits in different anatomical regions. These regions contain different circuits comprising unique cell types. An integral part to understanding neural circuits is a full census of the constituent parts, i.e., the neural cell types. This census can be based on different characteristics. Previously combinations of morphology and physiology, gene expression, and chromatin accessibility have been used in various cortical and subcortical regions. This has given an extensive yet incomplete overview of neural cell types. However, these techniques have not been applied to all brain regions. Here we apply single cell analysis of accessible chromatin on two similar but different cortical regions, the medial and the lateral entorhinal cortices. Even though these two regions are anatomically similar, their intrinsic and extrinsic connectivity are different. In 4136 cells we identify 20 different clusters representing different cell types. As expected, excitatory cells show regionally specific clusters, whereas inhibitory neurons are shared between regions. We find that several deep layer excitatory neuronal cell types as defined by chromatin profile are also shared between the two different regions. Integration with a larger scRNA-seq dataset maintains this shared characteristic for cells in Layer Vb. Interestingly, this Layer contains three clusters, two specific to either subregion and one shared between the two. These clusters can be putatively associated with particular functional and anatomical cell types found in this layer. This information is a step forwards into elucidating the cell types within the entorhinal circuit and by extension its functional underpinnings.

2021-12-28 | GSE192567 | GEO

Single cell transcriptomic and chromatin profiles suggest Layer Vb is the only layer with shared excitatory cell types in the medial and lateral entorhinal cortex

Project description:Single cell transcriptomic and chromatin profiles suggest Layer Vb is the only layer with shared excitatory cell types in the medial and lateral entorhinal cortex

| PRJNA791952 | ENA

Project description:Single cell transcriptomic and chromatin profiles suggest Layer Vb is the only layer with shared excitatory cell types in the medial and lateral entorhinal cortex.

| PRJNA786429 | ENA

The amyloid precursor protein regulates synaptic transmission at medial perforant path synapses

Project description:The perforant path provides the main cortical excitatory input to the hippocampus. Due to its important role in information processing and coding, entorhinal projections to the dentate gyrus have been studied in considerable detail. Nevertheless, a characterization of synaptic transmission between individual connected pairs of entorhinal stellate cells and dentate granule cells is still pending. Here, we have used organotypic entorhino-hippocampal tissue cultures, in which the entorhino-dentate (EC-GC) projection is present and EC-GC pairs can be studied using whole-cell patch clamp recordings. Using cultures of wildtype mice, the properties of EC-GC synapses formed by afferents from the lateral and medial entorhinal cortex were compared and differences in short-term plasticity were revealed. Since the perforant path is severely affected in Alzheimer´s disease, we used cultures of APP-deficient mice to address the role of the amyloid-precursor protein (APP) at this synapse. APP-deficiency caused alterations in excitatory neurotransmission at medial perforant path synapses that were accompanied by transcriptomic and ultrastructural changes. Moreover, the deletion of pre- but not postsynaptic APP through the local injection of Cre-expressing AAVs in conditional APPflox/flox tissue cultures increased the efficacy of neurotransmission at perforant path synapses. Together, these data suggest a physiological role for presynaptic APP at medial perforant path synapses, which may be adversely affected under conditions of altered APP processing.

2022-09-16 | GSE213284 | GEO

miRNA expression in rat medial entorhinal cortex layers during postnatal development

Project description:To examine how miRNAs differ between medial entorhinal cortex layers during postnatal development, we analyzed the miRNA expression in layer II and the deep layers (III-VI) at postnatal ages P2, P9, P23 and P45 in wildtype Long Evans rats. The expression of the two most significantly differentially expressed miRNAs were validated by in situ hybridization.

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Scytonema tolypothrichoides VB-61278

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Local projections of layer Vb-to-Va are more prominent in lateral than in medial entorhinal cortex.

Project description: Not available

| S-EPMC8051944 | biostudies-literature

Aberrant cortical layer development of brain organoids developed from Noonan syndrome-iPSCs

Project description:Noonan syndrome (NS) is a genetic disorder mainly caused by gain-of-function mutations of SHP2. Although diverse neurological manifestations are commonly diagnosed in NS patients, mechanisms on how the SHP2 mutation induces the neurodevelopmental defects remain elusive. Here, we report that cortical organoids (NS-COs) derived from NS-induced pluripotent stem cells (iPSCs) exhibit developmental abnormalities, especially in excitatory neurons (ENs). Although NS-COs normally develop in appearance, single-cell transcriptomic analysis represented increment of EN population and overexpression of cortical layer markers in NS-COs. Surprisingly, EN subpopulation co-expressing upper layer marker SATB2 and deep layer maker CTIP2 was enriched in NS-COs during the cortical development. In parallel with the developmental disruptions, NS-COs also exhibited reduced synaptic connectivity. Collectively, our findings suggest that perturbed cortical layer identity and impeded neuronal connectivity account for the neurological manifestations of NS.

2023-04-24 | GSE213798 | GEO

Excitatory SST neurons in the medial paralemniscal nucleus control repetitive self-grooming and encode reward

Project description:We revealed that the MPLSST neurons are excitatory neurons releasing neurotransmitter glutamate,and reveal that more than half of these neurons corelease neuropeptides SST and PTH2

2022-01-28 | GSE194338 | GEO

Activity-induced Nr4a1 regulates spine density and distribution pattern of excitatory synapses in pyramidal neurons

Project description:Excitatory synapses occur mainly on dendritic spines, and spine density is usually correlated with the strength of excitatory synaptic transmission. We report that Nr4a1, an activity-inducible gene encoding a nuclear receptor, regulates the density and distribution of dendritic spines in CA1 pyramidal neurons. Nr4a1 overexpression resulted in elimination of the majority of spines; however, postsynaptic densities were preserved on dendritic shafts, and the strength of excitatory synaptic transmission was unaffected, showing that excitatory synapses can be dissociated from spines. mRNA expression profiling studies suggest that Nr4a1-mediated transcriptional regulation of the actin cytoskeleton contributes to this effect. Under conditions of chronically elevated activity, when Nr4a1 was induced, Nr4a1 knockdown increased the density of spines and PSDs specifically at the distal ends of dendrites. Thus, Nr4a1 is a key component of an activity-induced transcriptional program that regulates the density and distribution of spines and synapses. After 10 days in culture, dissociated mouse hippocampal neurons in 6-well plates were infected with lentivirus expressing either Flag-Nr4a1 or GFP and incubated for 6 days to allow for transgene expression. Total RNA was then isolated using RNeasy Plus kit (QIAGEN). Samples passing an mRNA quality check proceeded to quantitative analysis on Agilent-026655 4x44 Mouse Microarrays.

2016-01-13 | E-GEOD-76805 | biostudies-arrayexpress

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