Ontology highlight
ABSTRACT:
PROVIDER: PRJNA544779 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9126580.fastq.gz | Fastqsanger.gz | |||
| SRR9126590.fastq.gz | Fastqsanger.gz | |||
| SRR9126581.fastq.gz | Fastqsanger.gz | |||
| SRR9126591.fastq.gz | Fastqsanger.gz | |||
| SRR9126582.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
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Project description:Synapses are organized into nanocolumns that control neurotransmission efficacy through precise alignment of postsynaptic AMPARs and presynaptic release sites. How these are trans-synaptically arranged remains elusive, despite evidence involving adhesion proteins. Highly enriched and confined at synapses, Leucine-Rich Repeat Transmembrane protein LRRTM2, is ideally poised to play this role by interacting with presynaptic Neurexins. Recent evidence show that LRRTM2 interacts with Neurexins through the C-terminal cap of LRRTM2 extracellular domain, but the role of this binding interface containing E348 has not been explored in synapse formation and function. Here, we developed a conditional knock-out mouse model (cKO) to address these questions and iden-tify LRRTM2 as a critical regulator of synapse nano-organization. We show that LRRTM2 cKO specifically impairs excitatory synapse formation and function. Surface expression, synaptic clustering, and membrane diffusion are tightly controlled by different motifs in LRRTM2 C-terminal domain, while the N-terminal domain controls pre-synapse nano-organization, AMPARs sub-positioning and stabilization, through the recently identified Neurexin-binding interface. Thus, LRRTM2 appears as a central organizer of synapse nanostructure through interaction with presynaptic Neurexins.
2024-09-18 | PXD054623 | Pride
Project description:The mechanism of chronic orofacial pain was investigated by examining the interaction between activated microglia, C1q and neurons in RVM of rats with orofacial pain caused by temporomandibular joint injection of CFA. The results demonstrated that the pain threshold in CFA group exhibited a continuous decline, reaching its lowest point on the third day. During the modeling process, administered daily stereotactic injections of ANX-005 and minocycline into the RVM, which resulted in a notable recovery in the rats' pain threshold and a significant increase in C1q/C3 and microglia in RVM of CFA rat. The application of ANX-005 or minocycline resulted in a reduction in the expression of C1q/C3 and microglia. Notably, the expression of excitatory presynaptic membrane markers reduced and the length and density of dendritic spines decreased on neurons in RVM. Additionally, C1q was abundantly localized on excitatory presynaptic membranes and expressed in microglial lysosomes. Treatment with ANX-005 or minocycline resulted in a reduced number of immunofluorescence colocalizations and an elevated dendritic spine density. These findings indicate that initial orofacial pain induced by CFA, microglia in RVM are involved in the pruning of excitatory presynaptic membranes through the complement C1q/C3-CR3 signaling pathway. This process results in a reduction in the proportion of excitatory synapses and a disruption in the physiological balance between RVM descending facilitation and descending inhibition. This leads to the predominance of descending facilitation in pain transmission in the RVM, which in turn facilitates the chronification of orofacial pain.
2025-01-27 | GSE287644 | GEO
Project description:Experience and activity-dependent transcription is a candidate mechanism to mediate development and refinement of specific cortical circuits. Here we provide evidence that the activity-dependent transcription factor Myocyte-Enhancer Factor 2C (MEF2C) is required in both presynaptic layer 4 (L4) and postsynaptic L2/3 somatosensory (S1) cortical neurons for development of their synaptic connection. In contrast, synaptic inputs from local L2/3, contralateral S1, or ipsilateral frontal/motor cortex are unaffected by postsynaptic Mef2c deletion in L2/3 neurons. Postsynaptic MEF2C is required for L4 to L2/3 synapse function during, but not after, an early postnatal, experience-dependent period. Furthermore, homozygous and heterozygous Mef2c deletion in presynaptic L4 neurons weakens L4 to L2/3 excitatory synaptic inputs by decreasing presynaptic release probability. Our results suggested that experience or activity-dependent transcriptional activation of MEF2C promotes development of L4→L2/3 synapses. In support of this idea, expression of transcriptionally active MEF2C (MEF2C-VP16) rescued weak L4 to L2/3 synaptic strength in sensory deprived mice. Consistent with a presynaptic function for MEF2C, we find that MEF2C regulates the activity-dependent expression of many presynaptic assembly genes, including transsynaptic cell adhesion proteins and regulators of neurotransmitter release. This work provides mechanistic insight into the experience-dependent development of specific cortical circuits.
2025-01-17 | GSE253629 | GEO
Project description:The paraventricular hypothalamus (PVH) is crucial for food intake control, yet the presynaptic mechanisms underlying PVH neurons remain unclear. Here, we show that RUVBL2 in the PVH is significantly reduced during energy deficit, and knockout (KO) of PVH RUVBL2 results in hyperphagic obesity in mice. RUVBL2-expressing neurons in the PVH (PVHRUVBL2) exert the anorexigenic effect by projecting to the arcuate hypothalamus, the dorsomedial hypothalamus, and the parabrachial complex. We further demonstrate that PVHRUVBL2 neurons form the synaptic connections with POMC and AgRP neurons in the ARC. PVH RUVBL2 KO impairs the excitatory synaptic transmission by reducing presynaptic boutons and synaptic vesicles near active zone. Finally, RUVBL2 overexpression in the PVH suppresses food intake and protects against diet induced obesity. Together, this study demonstrates an essential role for PVH RUVBL2 in food intake control, and suggests that modulation of synaptic plasticity could be an effective way to curb appetite and obesity.
2024-10-02 | GSE249791 | GEO
Project description:Reliable neurotransmission is dependent on coordinating entry of calcium into the terminal boutons of a presynaptic neuron with the exocytosis of vesicles into the synaptic cleft. This function fulfilled by an assembly of proteins in a specialized region of the presynaptic plasma membrane called the active zone (AZ). Here we use the fruit fly neuromuscular junction as a model synapse to test the consequences of specific depletion of two key AZ proteins, unc-13 and RIM-binding protein (Rbp), by RNAi knockdown on the transcriptome of these motor neurons. We find that decreased expression of Rbp results in concomittant decrease of expression in unc-13 and that the sets of differentially expressed genes between the two knockdowns are highly similar. We show that these knockdowns result in increased expression of genes involved in neuropeptide signalling, while reducing expression of other genes encoding the components of the AZ and voltage-gated K+ channels. Taken together, our findings suggest that knockdown of AZ components results in gene expression changes that bias the presynaptic neuron towards increased firing to compensate for the loss of AZs.
2024-08-28 | GSE250462 | GEO
Project description:Network hyperexcitability is manifested as frequent ictal discharges, often caused by unbalanced neurotransmission. We assessed synaptic changes in the hyperexcitable visual cortex of tetanus neurotoxin-injected mice (TeNT). A proteomics analysis of synaptic content revealed Carboxypeptidase E (CPE) up-regulation following TeNT injection. To quantify CPE effect on vesicle clustering, we used an ultrastructural measure of synaptic activity to investigate functional differences at excitatory and inhibitory synapses. We found homeostatic changes in hyperexcitable networks expressed as an early onset lengthening of active zones at inhibitory synapses followed by spatial reorganization at excitatory synapses. Moreover, inhibition of CPE decreases ictal discharges in vivo. This study reveals a complex landscape of homeostatic changes affecting the synaptic release machinery , differentially at inhibitory and excitatory terminals. We propose a novel homeostatic presynaptic mechanism which may impact release timing rather than synaptic strength.
2021-09-09 | PXD022270 | Pride
Project description:The neuromuscular junction (NMJ) is a specialized tripartite synapse composed of the motor axon terminal, covered by perisynaptic Schwann cells (PSCs), and the muscle fibre, separated by a basal lamina. It is exposed to different kind of injures such as mechanical traumas, pathogens including neurotoxins, and neuromuscular diseases such as amyotrophic lateral sclerosis and immune-mediated disorders, and has retained throughout vertebrate evolution an intrinsic ability for repair and regeneration, at variance from central synapses1. Following peripheral nerve injury, an intense but poorly defined crosstalk takes place at the NMJ among its components, functional to nerve terminal regeneration. To identify crucial factors released by PSCs and the muscle to induce nerve regrowth, we performed a transcriptome analysis of the NMJ at different time points after injection of -latrotoxin, a presynaptic neurotoxin isolated from the venom of the black widow spider. This toxin is a simple and controlled method to induce an acute, localized and reversible nerve terminal degeneration not blurred by inflammation, and can help to identify molecules involved in the intra- and inter-cellular signalling governing NMJ regeneration.
2017-05-30 | E-MTAB-5730 | biostudies-arrayexpress
Project description:LC-MS/MS-based proteomics method was used to study activity-dependent changes in the nuclear proteome and transcriptome of forebrain excitatory neurons during Pilocarpine-induced seizures.
2023-08-14 | PXD030637 | Pride
Project description:This is a model of one presynaptic and one postsynaptic cell, as described in the article:
Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model.
Wang XJ, Buzsáki G. J Neurosci. 1996 Oct 15;16(20):6402-13. PMID:8815919;
Abstract:
Fast neuronal oscillations (gamma, 20-80 Hz) have been observed in the neocortex and hippocampus during behavioral arousal. Using computer simulations, we investigated the hypothesis that such rhythmic activity can emerge in a random network of interconnected GABAergic fast-spiking interneurons. Specific conditions for the population synchronization, on properties of single cells and the circuit, were identified. These include the following: (1) that the amplitude of spike afterhyperpolarization be above the GABAA synaptic reversal potential; (2) that the ratio between the synaptic decay time constant and the oscillation period be sufficiently large; (3) that the effects of heterogeneities be modest because of a steep frequency-current relationship of fast-spiking neurons. Furthermore, using a population coherence measure, based on coincident firings of neural pairs, it is demonstrated that large-scale network synchronization requires a critical (minimal) average number of synaptic contacts per cell, which is not sensitive to the network size. By changing the GABAA synaptic maximal conductance, synaptic decay time constant, or the mean external excitatory drive to the network, the neuronal firing frequencies were gradually and monotonically varied. By contrast, the network synchronization was found to be high only within a frequency band coinciding with the gamma (20-80 Hz) range. We conclude that the GABAA synaptic transmission provides a suitable mechanism for synchronized gamma oscillations in a sparsely connected network of fast-spiking interneurons. In turn, the interneuronal network can presumably maintain subthreshold oscillations in principal cell populations and serve to synchronize discharges of spatially distributed neurons.
The presynaptic and postsynaptic cell have identical parameters and the variables in each cell are identified by using _pre or _post as a postfix to their names. The presynaptic cell influences the postsynaptic one via the synapse (variables and parameters: I_syn, E_syn, g_syn, F, theta_syn, alpha, beta). The applied current to the presynaptic cell, I_app_pre, is set to 2 microA/cm2 for 10 ms as in figure 1C of the article. The dependence of the postsynaptic cell on directly applied current can be investigated in isolation by setting I_app_pre to 0 and altering I_app_post.
Originally created by libAntimony v1.4 (using libSBML 3.4.1)
2024-09-02 | BIOMD0000000302 | BioModels
Project description:GABAB receptors (GBRs) are key regulators of synaptic release but little is known about trafficking mechanisms that control their presynaptic abundance. We now show that sequence-related epitopes in APP, AJAP-1 and PIANP bind with nanomolar affinities to the N-terminal sushi-domain of presynaptic GBRs. Of the three interacting proteins, selectively the genetic loss of APP impaired GBR-mediated presynaptic inhibition and axonal GBR expression. Proteomic and functional analyses revealed that APP associates with JIP and calsyntenin proteins that link the APP/GBR complex in cargo vesicles to the axonal trafficking motor. Complex formation with GBRs stabilizes APP at the cell surface and reduces proteolysis of APP to Aβ, a component of senile plaques in Alzheimer’s disease patients. Thus, APP/GBR complex formation links presynaptic GBR trafficking to Aβ formation. Our findings support that dysfunctional axonal trafficking and reduced GBR expression in Alzheimer’s disease increases Aβ formation.
2019-11-13 | PXD012487 | Pride