Virally Encoded Connectivity Transgenic Overlay RNA sequencing (VECTORseq) defines projection neurons involved in sensorimotor integration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA784983 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Purpose: Establish a high-throughput method to transcriptionally define projection neurons, VECTORseq, that reimagines transgenes expressed by widely used retrogradely infecting viruses as multiplexed RNA barcodes that are detected in single-cell sequencing. Methods: mRNA profiles of adult mouse brains Conclusions: Retrograde viruses express mRNA at levels detectable in single-cell sequencing. Different transgenes can be multiplexed in a single sequencing run. VECTORseq identifies both cortical and subcortical projection neurons. VECTORseq defined new superior colliculus and zona incerta projection populations. Established a high-throughput method to transcriptionally define projection neurons, VECTORseq, that reimagines transgenes expressed by widely used retrogradely infecting viruses as multiplexed RNA barcodes that are detected in single-cell sequencing.
2021-12-02 | GSE189907 | GEO
Project description: Not available
| S-EPMC8719358 | biostudies-literature
Project description:Sensorimotor reflex circuits engage distinct neuronal subtypes, defined by precise connectivity, to transform sensation into compensatory behavior. Whether and how motor partner populations shape the subtype fate and connectivity of their pre-motor counterparts remains controversial. Here, we discovered that motor partners are dispensable for proper connectivity across an entire vestibular reflex circuit that stabilizes gaze. We first measured activity following vestibular sensation in pre-motor projection neurons after constitutive loss of their extraocular motor neuron partners.We observed normal responses and topography consistent with unchanged functional connectivity between sensory neurons and projection neurons. Next, we show that projection neurons remain anatomically and molecularly poised to connect appropriately with their motor partners. Lastly, we show that the transcriptional signatures of projection neuron subtypes develop independently of motor partners. Our findings comprehensively overturn a long-standing model: that connectivity in the circuit for gaze stabilization is retrogradely determined by motor partner-derived signals. By defining the contribution of motor neurons to canonical sensorimotor circuit assembly, our work speaks to comparable processes in spinal circuits and advances our understanding of general principles of neural development.
2024-01-27 | GSE254345 | GEO
Project description:Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded Semaphorin3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a led to dysregulated α−motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of α−but not of adjacent γ−motor neurons. Additionally, a subset of TrkA+ sensory afferents projected to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement. 12 total samples consisting of three biological replicates each of flow sorted postnatal day 7 dorsal spinal cord astrocytes, ventral spinal cord astrocytes, dorsal SC non astrocytes, and ventral SC non astrocytes
2014-05-02 | E-GEOD-55054 | biostudies-arrayexpress
Project description:Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded Semaphorin3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a led to dysregulated α−motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of α−but not of adjacent γ−motor neurons. Additionally, a subset of TrkA+ sensory afferents projected to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement.
2014-05-02 | GSE55054 | GEO
Project description:Interconnectivity between neocortical areas is critical for sensory integration and sensorimotor transformations. These functions are mediated by heterogeneous interareal cortical projection neurons (ICPN), which send axon branches to distinct cortical areas as well as to subcortical targets. Although ICPN are anatomically diverse, they are molecularly homogeneous and how the diversity of their anatomical and functional features emerge during development remains largely unknown. Here, we address this question by linking connectome and transcriptome in developing single ICPN of the mouse neocortex using a combination of MAPseq mapping (to identify single-neuron axonal projections) and single-cell RNA sequencing (to identify corresponding gene expression). Focusing on neurons of the primary somatosensory cortex (S1), we reveal a protracted unfolding of the molecular and functional differentiation of motor cortex-projecting (M) compared to secondary somatosensory cortex-projecting (S2) ICPN. We identify SOX11 as a temporally differentially expressed transcription factor in M vs. S2 ICPN. Postnatal manipulation of SOX11 expression level in S1 impaired sensorimotor connectivity and selectively disrupted exploratory behavior in freely moving mice. Together, our results reveal that within a single cortical area, different subtypes of ICPN have distinct postnatal molecular differentiation paces, which is then reflected in distinct circuit connectivities and functions. Dynamic differences in expression levels of largely generic set of genes, rather than fundamental differences in the identity of developmental genetic programs, may thus account for emergence of intra-type diversity in cortical neurons.
2021-07-01 | GSE116944 | GEO
Project description:Interconnectivity between neocortical areas is critical for sensory integration and sensorimotor transformations. These functions are mediated by heterogeneous interareal cortical projection neurons (ICPN), which send axon branches to distinct cortical areas as well as to subcortical targets. Although ICPN are anatomically diverse, they are molecularly homogeneous and how the diversity of their anatomical and functional features emerge during development remains largely unknown. Here, we address this question by linking connectome and transcriptome in developing single ICPN of the mouse neocortex using a combination of MAPseq mapping (to identify single-neuron axonal projections) and single-cell RNA sequencing (to identify corresponding gene expression). Focusing on neurons of the primary somatosensory cortex (S1), we reveal a protracted unfolding of the molecular and functional differentiation of motor cortex-projecting (M) compared to secondary somatosensory cortex-projecting (S2) ICPN. We identify SOX11 as a temporally differentially expressed transcription factor in M vs. S2 ICPN. Postnatal manipulation of SOX11 expression level in S1 impaired sensorimotor connectivity and selectively disrupted exploratory behavior in freely moving mice. Together, our results reveal that within a single cortical area, different subtypes of ICPN have distinct postnatal molecular differentiation paces, which is then reflected in distinct circuit connectivities and functions. Dynamic differences in expression levels of largely generic set of genes, rather than fundamental differences in the identity of developmental genetic programs, may thus account for emergence of intra-type diversity in cortical neurons.
2021-07-01 | GSE118681 | GEO
Project description:Interconnectivity between neocortical areas is critical for sensory integration and sensorimotor transformations. These functions are mediated by heterogeneous interareal cortical projection neurons (ICPN), which send axon branches to distinct cortical areas as well as to subcortical targets. Although ICPN are anatomically diverse, they are molecularly homogeneous and how the diversity of their anatomical and functional features emerge during development remains largely unknown. Here, we address this question by linking connectome and transcriptome in developing single ICPN of the mouse neocortex using a combination of MAPseq mapping (to identify single-neuron axonal projections) and single-cell RNA sequencing (to identify corresponding gene expression). Focusing on neurons of the primary somatosensory cortex (S1), we reveal a protracted unfolding of the molecular and functional differentiation of motor cortex-projecting (M) compared to secondary somatosensory cortex-projecting (S2) ICPN. We identify SOX11 as a temporally differentially expressed transcription factor in M vs. S2 ICPN. Postnatal manipulation of SOX11 expression level in S1 impaired sensorimotor connectivity and selectively disrupted exploratory behavior in freely moving mice. Together, our results reveal that within a single cortical area, different subtypes of ICPN have distinct postnatal molecular differentiation paces, which is then reflected in distinct circuit connectivities and functions. Dynamic differences in expression levels of largely generic set of genes, rather than fundamental differences in the identity of developmental genetic programs, may thus account for emergence of intra-type diversity in cortical neurons.
2021-07-01 | GSE156080 | GEO
Project description:Purpose:This work aimed to identify the genetic profiles of piriform projection neurons and characterize their spatial organization within the piriform cortex. Methods: We microdissected the three layers of pirifrom cortex by laser capture (LMD) and performed RNA deep sequencing in order to identify layer-specific molecular markers, we then validated these data by using RNA in situ hybridization and immunohistochemistry.We next performed anterograde neural tracing experiments to identify piriform target regions, and retrograde neural tracing experiments to analyze how piriform projection neurons are organized within piriform cortex.We then combined the analysis of patterns of gene expression with retrograde tracing experiments to identify molecular signatures of the different subclasses of piriform projecting neurons. Results:We show that layers and sub-layers of the piriform cortex can be discriminated by gene expression patterns in adult piriform cortex. We observe that neurons projecting to distinct target areas are localized in distinct layers and express specific genes. We demonstrate that these molecular signatures of piriform projection neurons are maintained in reeler mice, in which cortical lamination is lost and neural positioning is scrambled, suggesting that piriform output connectivity strictly depends on the molecular programm, rather than a proper lamination of the cortex. Conclusion:These results provide important insights into the principles underling the piriform connectivity.
2016-07-13 | GSE70800 | GEO
Project description:Deciphering patterns of connectivity between neurons in the mammalian brain is a critical step toward understanding brain function. Conventional imaging based neuroanatomical tracing methods identify area-to-area or sparse neuron-to-neuron connectivity patterns, but with extremely limited throughput. Recently developed barcode-based connectomics methods can efficiently map large numbers of single-neuron projections, but linking these data to single-cell transcriptomics remains a challenge. Here, we established a retro-AAV barcode-based multiplexed tracing method called MERGE-seq (Multiplexed projection neuRons retroGrade barcodE sequencing), which is capable of simultaneously characterizing the projectome and transcriptome at the single neuron level. We uncovered dedicated and collateral projection patterns of ventromedial prefrontal cortex (vmPFC) neurons to five downstream targets (AI, DMS, BLA, MD and LH). We found that projection-defined vmPFC neurons are molecularly heterogeneous, which are composed of different neuronal subtypes. We further identified transcriptional signatures of various dedicated and bifurcated vmPFC neurons, and verified Pou3f1 as the marker gene of neurons sending collateral axons to DMS and LH. Finally, we fitted our single-neuron connectome/transcriptome data into a machine learning-based model and revealed groups of genes that were predictive of certain projection pattern. In summary, we have developed a new multiplexed technique whose paired connectome and gene expression data can help reveal organizational principles that form neural circuits and process information.
2024-02-25 | GSE210172 | GEO