Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits

ABSTRACT: How neuronal connections are established and organized in functional networks determines brain function. In the mouse cerebral cortex, different classes of GABAergic interneurons exhibit specific connectivity patterns that underlie their ability to shape temporal dynamics and information processing. Much progress has been made parsing interneuron diversity, yet the molecular mechanisms by which interneuron subtype-specific connectivity motifs emerge remain unclear. Here we investigate transcriptional dynamics in different classes of interneurons during the formation of cortical inhibitory circuits. We found that whether the interneurons synapse with pyramidal neurons on their dendrites, soma, or axon initial segment is determined by synaptic molecules that are expressed in a subtype-specific manner. Thus cell-specific molecular programs that unfold during early postnatal development underlie the connectivity patterns of cortical interneurons.

ORGANISM(S): Mus musculus

PROVIDER: GSE120161 | GEO | 2019/01/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Rbfox1 mediates cell-type specific splicing in cortical interneurons

Project description:Cortical interneurons display a remarkable diversity in their morphology, physiological properties and connectivity. Elucidating the molecular determinants underlying this heterogeneity is essential for understanding interneuron development and function. We discovered that alternative splicing differentially regulates the integration of somatostatin- and parvalbumin-expressing interneurons into nascent cortical circuits through the cell-type specific tailoring of mRNAs. Specifically, we identified a role for the activity-dependent splicing regulator Rbfox1 in the development of cortical interneuron subtype specific efferent connectivity. Our work demonstrates that Rbfox1 mediates largely non-overlapping alternative splicing programs within two distinct but related classes of interneurons.

2018-10-12 | GSE119998 | GEO

Comparative analysis of different cortical interneuron groups.

Project description:GABAergic interneuron in the cortex comprise a very heterogenous group. and it is critical to identify discrete interneuron types to understand how their contributions to behavior can be modulated by external and internal cues. However, molecular difinition of these interneuron cell groups has been difficult. Comparative analysis of different interneuron subtypes can provide us new candidate marker genes which could target more specific interneu?on cell group. Here we identify oxytocin responsive novel class of interneuron through our comparative analysis. We employed the bacTRAP strategy, which uses BAC transgenic mice expressing EGFP-tagged ribosomal protein L10a in specific cell populations, to affinity purify polysome-bound mRNAs from Nek7, Dlx1, Cort, Htr3a, Oxtr expressing cortical interneurons. We show that Oxtr expressing cells are a subtype of somatostatin positive interneurons. Three independent TRAP replicates were collected and total RNA from the immunoprecipitates or flow-through (input) whole cortex lysates were amplified and hybridized. Data were normalized with the GCRMA algorithm and replicates were averaged across conditions. We recommend filtering data to remove probe sets with normalized expression values less than 50 in at least one condition. Because the Nek7 BAC labels non-neuronal cells, we recommend to delete astrocytes and oligodendrocytes genes from the list using GSE13379 data.

2014-10-07 | E-GEOD-56996 | biostudies-arrayexpress

Comparative analysis of different cortical interneuron groups.

2014-10-07 | GSE56996 | GEO

Transcriptional maintenance of cortical somatostatin interneuron subtype identity during migration

Project description:Cortical interneuron diversity arises from the interplay of intrinsic developmental patterning and local extrinsic cues. While individual genetic programs underlying cardinal cell type identity are established in immature neurons prior to integration into cortical circuits, it remains unclear whether distinct interneuron subtype identities are pre-established, and if so, how their identity is maintained prior to circuit integration. Sox6 is a transcription factor with an established role in the maturation of interneurons derived from the medial ganglionic eminence and cell-type specification in other neuronal and non-neuronal cells. To determine a possible role in maintaining cortical somatostatin-expressing (Sst+) interneuron subtype identity, we conditionally removed Sox6 (Sox6-cKO) in migrating Sst+ interneurons and assessed the effects on their mature identity. In adolescent animals, five of eight molecular Sst+ subtypes were nearly absent in the cortex of Sox6-cKO mice. This reduced subtype diversity was not due to a decrease in the overall number of Sst+ interneurons and cells displayed electrophysiological maturity and expressed genes enriched within the broad class of Sst+ interneurons. Furthermore, we show that at embryonic day 18.5, prior to cortical integration, mature Sst+ cell subtype identity could already be inferred in both control and Sox6-cKO cortices, suggesting that the loss in subtype diversity observed in the mature cortex is due to a disrupted subtype maintenance. Importantly, Sox6 removal at postnatal day 7, after Sst+ interneurons have finished migrating and begun integration into the network, did not disrupt marker expression of Sst+ subtypes in the mature cortex. Therefore, Sox6 is necessary during this migratory phase for maintenance of Sst+ subtypes identity, indicating that subtype maintenance requires active transcriptional programs during migration.

2023-08-25 | GSE233791 | GEO

DOT1L deletion impairs the development of cortical Parvalbumin-expressing interneurons

Project description:Our group has reported that the histone methyltransferase DOT1L is necessary for proper cortical plate development and layer distribution of glutamatergic neurons, however, its specific role on cortical interneuron development has not yet been explored. Here, we demonstrate that DOT1L affects interneuron development in a cell-autonomous manner. Deletion of Dot1l in MGE-derived interneuron precursor cells results in an overall reduction and altered distribution of GABAergic interneurons in the cortical plate at postnatal day (P) 0. Furthermore, we observed an altered proportion of GABAergic interneurons in the cortex and striatum at P21 with a significant decrease in Parvalbumin (PVALB)-expressing interneurons. Altogether, our results indicate that reduced numbers of cortical interneurons upon DOT1L deletion results from altered postmitotic differentiation/maturation.

2023-08-01 | GSE221994 | GEO

Early emergence of cortical interneuron diversity in the mouse embryo

Project description:GABAergic interneurons play crucial roles in the regulation of neural circuit activity in the cerebral cortex. A hallmark of cortical interneurons is their remarkable structural and functional diversity, yet the molecular determinants and the precise timing underlying their diversification remain largely unknown. Here we use single-cell transcriptomics to identify distinct types of progenitor cells and newborn neurons in the ganglionic eminences, the embryonic proliferative regions that give rise to cortical interneurons. These embryonic precursors define temporally and spatially restricted transcriptional trajectories that unambiguously relate to specific classes of interneurons in the adult cerebral cortex. Our findings therefore suggest that interneuron diversity is already patent shortly after neurons become postmitotic through the acquisition of specific transcriptional programs that unfold over several weeks in the developing cortex

2018-03-06 | GSE109796 | GEO

Sonic hedgehog Activation Restores Interneurons and Cognitive Function in Newborns with Intraventricular Hemorrhage

Project description:We hypothesized that the occurrence of IVH would reduce interneuron neurogenesis in the medial ganglionic eminence and diminish the population of parvalbumin+ and somatostatin+ cortical interneurons. Since Sonic Hedgehog promotes the production of cortical interneurons, we also postulated that the activation of Sonic Hedgehog signaling might restore neurogenesis, cortical interneuron population, and neurobehavioral function in premature newborns with IVH.

2022-08-06 | GSE210477 | GEO

Medial Ganglionic Eminence and Cortical Organoids Model Human Brain Development and Interneuron Migration [RNA-seq2]

Project description:Organoid techniques provide unique platforms to model brain development and neurological disorders. While organoids recapitulating corticogenesis were established, a system modeling human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and related lineages, remains to be developed. Here, we describe a system to generate MGE or cortex-specific organoids from human pluripotent stem cells. These organoids recapitulate the developments of MGE and cortex domains respectively. Population and single-cell transcriptomic profiling revealed transcriptional dynamics and lineage productions during MGE and cortical organoids development. Chromatin accessibility landscapes were found to be involved in this process. Furthermore, MGE and cortical organoids generated physiologically functional neurons and neuronal networks. Finally, we applied fusion organoids as a model to investigate human interneuron migration. Together, our study provides a new platform for generating domain-specific brain organoids, for modeling human interneuron migration, and offers deeper insight into molecular dynamics during human brain development.

2017-07-21 | GSE98201 | GEO

Medial Ganglionic Eminence and Cortical Organoids Model Human Brain Development and Interneuron Migration [RNA-seq]

2017-07-21 | GSE97881 | GEO

Medial Ganglionic Eminence and Cortical Organoids Model Human Brain Development and Interneuron Migration [ATAC-seq]

2017-07-21 | GSE97880 | GEO