Neurexin-3 defines synapse- and sex-dependent diversity of GABAergic inhibition in ventral subiculum
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ABSTRACT:
PROVIDER: PRJNA720923 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14197700_1.fastq.gz | Fastqsanger.gz | |||
| SRR14197700_2.fastq.gz | Fastqsanger.gz | |||
| SRR14197701_1.fastq.gz | Fastqsanger.gz | |||
| SRR14197701_2.fastq.gz | Fastqsanger.gz | |||
| SRR14197702_1.fastq.gz | Fastqsanger.gz |
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Project description:Ventral subiculum (vSUB) is integral to the regulation of stress and reward, however the intrinsic connectivity and synaptic properties of the inhibitory microcircuit are poorly understood. Neurexin-3 (Nrxn3) is highly expressed in hippocampal inhibitory neurons, but its function at inhibitory synapses has remained elusive. Using slice electrophysiology, imaging, and single-cell RNA sequencing, we identify multiple roles for Nrxn3 at GABAergic parvalbumin (PV) interneuron synapses made onto vSUB regular spiking (RS) and burst spiking (BS) principal neurons. Surprisingly, we found that intrinsic connectivity of vSUB and synaptic function of Nrxn3 in vSUB are sexually dimorphic. We reveal that vSUB PVs make preferential contact with RS neurons in males, but BS neurons in females. Furthermore, we determined that despite comparable Nrxn3 isoform expression in male and female PV neurons, Nrxn3 maintains synapse density at PV-RS synapses in males, but suppresses presynaptic release at the same synapses in females.
2021-12-09 | GSE171793 | GEO
Project description:Ventral subiculum (vSUB) is integral to the regulation of stress and reward; however, the intrinsic connectivity and synaptic properties of the inhibitory local circuit are poorly understood. Neurexin-3 (Nrxn3) is highly expressed in hippocampal inhibitory neurons, but its function at inhibitory synapses has remained elusive. Using slice electrophysiology, imaging, and single-cell RNA sequencing, we identify multiple roles for Nrxn3 at GABAergic parvalbumin (PV) interneuron synapses made onto vSUB regular-spiking (RS) and burst-spiking (BS) principal neurons. Surprisingly, we find that intrinsic connectivity of vSUB and synaptic function of Nrxn3 in vSUB are sexually dimorphic. We reveal that PVs make preferential contact with RS neurons in male mice, but BS neurons in female mice. Furthermore, we determine that despite comparable Nrxn3 isoform expression in male and female PV neurons, Nrxn3 knockout impairs synapse density, postsynaptic strength, and inhibitory postsynaptic current (IPSC) amplitude at PV-RS synapses in males, but enhances presynaptic release and IPSC amplitude in females.
| S-EPMC8763380 | biostudies-literature
Project description:Diversification of cell adhesion molecules by alternative splicing is proposed to underlie molecular codes for neuronal wiring. Transcriptomic approaches mapped detailed cell type-specific mRNA splicing programs. However, it has been hard to probe synapse-specific localization and function of the resulting protein splice isoforms, or “proteoforms”, in vivo. We here apply a proteoform-centric workflow in mice to test synapse-specific functions of splice isoforms of the synaptic adhesion molecule Neurexin-3 (NRXN3). We uncover a major proteoform, NRXN3 AS5, that is highly expressed in GABAergic interneurons and dendrite-targeting GABAergic terminals. NRXN3 AS5 abundance significantly diverges from the distribution of the Nrxn3 mRNA and is gated by translation-repressive elements. Nrxn3 AS5 isoform deletion results in selective impairment of dendrite-targeting interneuron synapses in the dentate gyrus without affecting somatic inhibition or glutamatergic perforant-path synapses. This work establishes cell- and synapse-specific functions of a specific neurexin proteoform and highlights the importance of alternative splicing regulation for synapse specification.
2022-02-11 | PXD031379 | Pride
Project description:single-cell RNA sequencing data (plate-based CelSeq2) of developing mouse ventral midbrain GABAergic neurons. vmbGABA series contains E16 and P0 VGAT mouse ventral midbrain and E16 and P0 VGAT/PITX3 co-expressing mouse ventral midbrain.
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Project description:Neurexins are key synaptic organizers which exist in thousands of alternatively spliced isoforms. Because trans-synaptic neurexin interactions with different post-synaptic molecules are largely isoform dependent, a cell type-level census of different neurexin isoforms could predict molecular interactions relating to synapse identity and function. Using single-cell transcriptomics to study the origin of neurexin diversity in multiple murine hippocampal and cortical cell types, we have discovered shared expression patterns in developmentally-related cell types. By comparing neurexin profiles in immature embryonic neurons, we show that neurexin profiles are specified during early development and remain unchanged throughout neuronal maturation. In contrast to this, we find that expression of other cell-adhesion molecules is modulated throughout circuit maturation. Thus, our findings reveal that ontogenetic stability of neurexin expression is unique among the broader landscape of cell-adhesion molecules, whose coordinated expression progressively governs the emergence of cell type identity.
2019-06-23 | GSE121653 | GEO
Project description:Molecular diversity and migration of GABAergic neurons in the developing ventral midbrain
| PRJNA1116748 | ENA
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:Six DD class GABAergic neurons are generated in the embryo to synapse with ventral muscles and receive input from cholinergic neurons in the dorsal nerve cord. After hatching and toward the end of the first larval (L1) stage, DD neurons reverse polarity (i.e., synapse with dorsal muscles, receive ventral cholinergic inputs). Expression profiles were generated from DD neurons in the early L1 stage before the initiation of the remodeling program. We used microarray analysis to detect transcripts with potential roles in DD remodeling. We used FACS to isolate ttr-39::mCherry labeled DD GABAergic motor neurons from a synchronized population of L1 larvae and amplified and labeled total RNA to generate Affymetrix Genome Array data. The DD data sets were compared to an expression profile obtained from all cells in a matched population of synchronized L1 larvae. See Spencer et al. PLOS One 9, e112102 (2014).
2015-08-01 | E-GEOD-71618 | biostudies-arrayexpress
Project description:Abstract Background Neurexins are proteins located in the presynaptic membrane that bind postsynaptic ligands, neuroligins, neurexophilins, and dystrophoglycan. They exert profound effects on neurological function by mediating signalling across synapses and determining synaptic characteristics through the recruitment of additional proteins for synapse formation. Alterations in neurexin-encoding genes cause cognitive disorders such as autism, developmental delay and schizophrenia. The three neurexin genes in the human genome (NRXN1, NRXN2, and NRXN3) each have two different functional promoters, producing a large (alpha) and small (beta) transcript with corresponding proteins. NRXN1 produces hundreds, perhaps thousands, of different transcripts with differential localization in the CNS. Results We report here the identification of an individual (53825) with mild dysmorphia, severe language disorder, mild intellectual disability, attention deficit hyperactivity disorder (ADHD), and a mood disorder. Genomic analysis by Affymetrix 6.0 Gene Chip and FISH (fluorescence in situ hybridization) using probes specific for NRXN1 revealed a hemizygous deletion of approximately 190 Kb, which includes exons 3-5 of NRXN1. This deletion should result in the absence of the vast majority of different NRXN1 alpha transcripts from one of the NRXN1 gene copies, without effecting NRXN1 beta transcription. Copy number analysis of Affymetrix 6.0 SNP arrays was performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples for pediatric patients. One sample showed partial deletion of NRXN1 alpha; data presented in this Series.
2011-06-24 | E-GEOD-23358 | biostudies-arrayexpress
Project description:Abstract Background Neurexins are proteins located in the presynaptic membrane that bind postsynaptic ligands, neuroligins, neurexophilins, and dystrophoglycan. They exert profound effects on neurological function by mediating signalling across synapses and determining synaptic characteristics through the recruitment of additional proteins for synapse formation. Alterations in neurexin-encoding genes cause cognitive disorders such as autism, developmental delay and schizophrenia. The three neurexin genes in the human genome (NRXN1, NRXN2, and NRXN3) each have two different functional promoters, producing a large (alpha) and small (beta) transcript with corresponding proteins. NRXN1 produces hundreds, perhaps thousands, of different transcripts with differential localization in the CNS. Results We report here the identification of an individual (53825) with mild dysmorphia, severe language disorder, mild intellectual disability, attention deficit hyperactivity disorder (ADHD), and a mood disorder. Genomic analysis by Affymetrix 6.0 Gene Chip and FISH (fluorescence in situ hybridization) using probes specific for NRXN1 revealed a hemizygous deletion of approximately 190 Kb, which includes exons 3-5 of NRXN1. This deletion should result in the absence of the vast majority of different NRXN1 alpha transcripts from one of the NRXN1 gene copies, without effecting NRXN1 beta transcription.
2011-06-25 | GSE23358 | GEO