Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neuroligin 3 Splice Isoforms Shape Mouse Hippocampal Inhibitory Synaptic Function

ABSTRACT: Neuroligin 3 Splice Isoforms Shape Mouse Hippocampal Inhibitory Synaptic Function

PROVIDER: PRJNA599927 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR10850815_1.fastq.gz	Fastqsanger.gz
	SRR10850815_2.fastq.gz	Fastqsanger.gz
	SRR10850816_1.fastq.gz	Fastqsanger.gz
	SRR10850816_2.fastq.gz	Fastqsanger.gz
	SRR10850817_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 8

Similar Datasets

Neuroligin 3 Splice Isoforms Shape Mouse Hippocampal Inhibitory Synaptic Function

Project description:Synapse formation is a dynamic process essential for neuronal circuit development and maturation. At the synaptic cleft, trans-synaptic protein-protein interactions constitute major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity and its dysregulation has been implicated in neurodevelopmental disorders including autism spectrum disorders. However, the molecular mechanisms underlying E-I balance remains to be elucidated. Here, we investigate Neuroligin (Nlgn) genes which encode a family of postsynaptic adhesion molecules that shape excitatory and inhibitory synaptic function. We identified that NLGN3 protein differentially regulates inhibitory synaptic transmission in a splice isoform-dependent manner in hippocampal CA1 synapses. Distinct subcellular localization patterns of NLGN3 isoforms contribute to the functional differences observed among splice variants. Finally, our single-cell sequencing analysis reveals that Nlgn1 and Nlgn3 are the major Nlgn genes and that Nlgn splice isoforms are highly diverse in CA1 pyramidal neurons.

2020-05-05 | GSE143295 | GEO

Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus.

Project description:Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, trans-synaptic protein-protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry, and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate neuroligin (Nlgn) genes that encode a family of postsynaptic adhesion molecules known to shape excitatory and inhibitory synaptic function. We demonstrate that the NLGN3 protein differentially regulates inhibitory synaptic transmission in a splice isoform-dependent manner at hippocampal CA1 synapses. We also found that distinct subcellular localizations of the NLGN3 isoforms contribute to the functional differences observed among these isoforms. Finally, results from single-cell RNA-Seq analyses revealed that Nlgn1 and Nlgn3 are the major murine Nlgn genes and that the expression levels of the Nlgn splice isoforms are highly diverse in CA1 pyramidal neurons. Our results delineate isoform-specific effects of Nlgn genes on the E-I balance in the murine hippocampus.

| S-EPMC7307194 | biostudies-literature

Neuroligin-4 Regulates Excitatory Synaptic Transmission in Human Neurons

Project description:The autism-associated synaptic-adhesion gene Neuroligin-4 (NLGN4) is poorly conserved evolutionarily, limiting conclusions from Nlgn4 mouse models for human cells. Here, we show that the cellular and subcellular expression of human and murine Neuroligin-4 differ, with human Neuroligin-4 primarily expressed in cerebral cortex and localized to excitatory synapses. Overexpression of NLGN4 in human neurons resulted in an increase in excitatory synapse numbers but a remarkable decrease in synaptic strength. Human neurons carrying the syndromic autism mutation NLGN4-R704C also formed more excitatory synapses but with increased functional synaptic transmission due to a postsynaptic mechanism, while genetic loss of NLGN4 did not significantly affect synapses in the human neurons analyzed. Thus, the NLGN4-R704C mutation represents a change of function mutation. Our work reveals contrasting roles of NLGN4 in human and mouse neurons, suggesting human evolution has impacted even fundamental cell biological processes generally assumed to be highly conserved.

2019-06-27 | GSE131428 | GEO

Modeling Synaptic Mechanisms of Autism-associated Neuroligin-3 R451C Mutation Using Human Neurons

Project description:Synaptic dysfunction represents a key pathophysiology in neurodevelopmental disorders such as autism spectrum disorder (ASD). Rare mutation R451C in human Neuroligin 3 (NLGN3, encoded by X-linked gene NLGN3), a cell adhesion molecule essential for synapse formation, has been linked to ASD. Despite success in recapitulating the social interaction behavioral deficits and the underlying synaptic abnormalities in mouse model, the impact of NLGN3 R451C on the human neuronal system remains elusive. Here, we generated isogenic knock-in human pluripotent stem cell lines harboring NLGN3 R451C allele and examined its impact on synaptic transmission. Analysis of co-cultured excitatory and inhibitory induced neurons (iNs) with mutation revealed an augmentation in excitatory synaptic strength comparing to isogenic control, but not in inhibitory synaptic transmission. Consistently, the augmentation in excitatory transmission was confirmed in iNs transplanted into mouse forebrain. Using single-cell RNA seq on co-cultured excitatory and inhibitory iNs, we identified differential expression genes (DEGs) and found NLGN3 R451C alters gene networks associated with synaptic transmission. Gene ontology and enrichment analysis revealed convergent gene networks associated with ASD and other mental disorders. Our finding suggests that the NLGN3 R451C mutation could preferentially impact excitatory neurons, which causes overall network properties changes and excitation-inhibition imbalance related to mental disorders.

2022-10-26 | GSE180751 | GEO

Drosophila SWR1 and NuA4 complexes originate from DOMINO splice isoforms

Project description:Drosophila SWR1 and NuA4 complexes originate from DOMINO splice isoforms

| PRJNA608021 | ENA

RNA-seq of 293T cells expressing different RUNX1 splice isoforms

Project description:RNA-seq of 293T cells expressing different RUNX1 splice isoforms

| PRJEB53818 | ENA

Neuroligin-4 Regulates Excitatory Synaptic Transmission in Human Neurons

Project description:Neuroligin-4 Regulates Excitatory Synaptic Transmission in Human Neurons

| PRJNA543517 | ENA

Proteomic maps of excitatory and inhibitory synaptic clefts revealed by proximity biotinylation

Project description:Loh KH, Stawski PS, Draycott AS, Udeshi ND, Lehrman EK, Wilton DK, Svinkina T, Deerinck TJ, Ellisman MH, Stevens B, Carr SA, Ting AY. Cell 2016 Excitatory synapses are connections between neurons that promote the propagation of action potentials while inhibitory synapses repress them. Normal brain function relies on the careful balance of these antagonistic connections, which occur via molecularly distinct synaptic clefts. Understanding how this is achieved relies on knowledge of their protein compositions, yet the clefts remain uncharacterized because they cannot be isolated biochemically. Here, we mapped the proteomes of two of the most common excitatory and inhibitory synaptic clefts in living neurons, using a spatially restricted enzymatic tagging strategy. These proteomes reveal dozens of novel synaptic candidates, and assign numerous known synaptic proteins to a specific cleft type. The molecular differentiation of each cleft allowed us to identify Mdga2 as a specificity factor regulating the presynaptic neurotransmitter recruiting activity of Neuroligin-2 at inhibitory synapses.

2016-06-23 | MSV000079849 | MassIVE

Drosophila SWR1 and NuA4 complexes originate from DOMINO splice isoforms [ChIP-seq]

Project description:Drosophila SWR1 and NuA4 complexes originate from DOMINO splice isoforms [ChIP-seq]

| PRJNA608023 | ENA

Drosophila SWR1 and NuA4 complexes originate from DOMINO splice isoforms [RNA-seq]

Project description:Drosophila SWR1 and NuA4 complexes originate from DOMINO splice isoforms [RNA-seq]

| PRJNA606578 | ENA