scholarly journals Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement

2018 ◽  
Vol 115 (5) ◽  
pp. E1051-E1060 ◽  
Author(s):  
Brian T. Kalish ◽  
Lucas Cheadle ◽  
Sinisa Hrvatin ◽  
M. Aurel Nagy ◽  
Samuel Rivera ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Lateral Geniculate Nucleus ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Lateral Geniculate ◽  
Circuit Development ◽  
Circuit Assembly ◽  
Relay Neurons

Coordinated changes in gene expression underlie the early patterning and cell-type specification of the central nervous system. However, much less is known about how such changes contribute to later stages of circuit assembly and refinement. In this study, we employ single-cell RNA sequencing to develop a detailed, whole-transcriptome resource of gene expression across four time points in the developing dorsal lateral geniculate nucleus (LGN), a visual structure in the brain that undergoes a well-characterized program of postnatal circuit development. This approach identifies markers defining the major LGN cell types, including excitatory relay neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells. Most cell types exhibit significant transcriptional changes across development, dynamically expressing genes involved in distinct processes including retinotopic mapping, synaptogenesis, myelination, and synaptic refinement. Our data suggest that genes associated with synapse and circuit development are expressed in a larger proportion of nonneuronal cell types than previously appreciated. Furthermore, we used this single-cell expression atlas to identify the Prkcd-Cre mouse line as a tool for selective manipulation of relay neurons during a late stage of sensory-driven synaptic refinement. This transcriptomic resource provides a cellular map of gene expression across several cell types of the LGN, and offers insight into the molecular mechanisms of circuit development in the postnatal brain.

MO262THE SINGLE-CELL TRANSCRIPTOMICS OF HUMAN IGA NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yong Zhong ◽  
Xiangcheng Xiao
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Signaling Pathways ◽  
Iga Nephropathy ◽  
Molecular Mechanisms ◽  
Mesangial Cells ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Receptor Crosstalk ◽  
Overt Proteinuria

Abstract Background and Aims The exact molecular mechanisms underlying IgA nephropathy (IgAN) remains incompletely defined. Therefore, it is necessary to further elucidate the mechanism of IgA nephropathy and find novel therapeutic targets. Method Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from 4 IgAN and 1 control subjects to define the transcriptomic landscape at the single-cell resolution. Unsupervised clustering analysis of kidney specimens was used to identify distinct cell clusters. Differentially expressed genes and potential signaling pathways involved in IgAN were also identified. Results Our analysis identified 14 cell subsets in kidney biopsies from IgAN patients, and analyzed changing gene expression in distinct renal cell types. We found increased mesangial expression of several novel genes including MALAT1, GADD45B, SOX4 and EDIL3, which were related to proliferation and matrix accumulation and have not been reported in IgAN previously. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling and NOD-like receptor signaling. Moreover, the receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. Specifically, IgAN with overt proteinuria displayed elevated genes participating in several signaling pathways which may be involved in pathogenesis of progression of IgAN. Conclusion The comprehensive analysis of kidney biopsy specimen demonstrated different gene expression profile, potential pathologic ligand-receptor crosstalk, signaling pathways in human IgAN. These results offer new insight into pathogenesis and identify new therapeutic targets for patients with IgA nephropathy.

scholarly journals Single-cell RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates and humans

2020 ◽  
Author(s):  
Trygve E. Bakken ◽  
Cindy T.J. van Velthoven ◽  
Vilas Menon ◽  
Rebecca D. Hodge ◽  
Zizhen Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Visual Information ◽  
Cell Types ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Cortical Projection ◽  
Significant Differential Expression ◽  
Cellular Expression ◽  
Dominant Feature ◽  
Parvocellular Neurons ◽  
Relay Neurons

ABSTRACTAbundant anatomical and physiological evidence supports the presence of at least three distinct types of relay glutamatergic neurons in the primate dorsal lateral geniculate nucleus (dLGN) of the thalamus, the brain region that conveys visual information from the retina to the primary visual cortex. Relay neuron diversity has also been described in the mouse dLGN (also known as LGd). Different types of relay neurons in mice, humans and macaques have distinct morphologies, distinct connectivity patterns, and convey different aspects of visual information to the cortex. To investigate the molecular underpinnings of these cell types, and how these relate to other cellular properties and differences in dLGN between human, macaque, and mice, we profiled gene expression in single nuclei and cells using RNA-sequencing. These efforts identified four distinct types of relay neurons in the primate dLGN, magnocellular neurons, parvocellular neurons, and two cell types expressing canonical marker genes for koniocellular neurons. Surprisingly, despite extensive documented morphological and physiological differences between magno- and parvocellular neurons, we identified few genes with significant differential expression between transcriptomic cell types corresponding to these two neuronal populations. We also detected strong donor-specific gene expression signatures in both macaque and human relay neurons. Likewise, the dominant feature of relay neurons of the adult mouse dLGN is high transcriptomic similarity, with an axis of heterogeneity that aligns with core vs. shell portions of mouse dLGN. Together, these data show that transcriptomic differences between principal cell types in the mature mammalian dLGN are subtle relative to striking differences in morphology and cortical projection targets. Finally, we align cellular expression profiles across species and find homologous types of relay neurons in macaque and human, and distinct relay neurons in mouse.

Cholinergic influence of the laterodorsal tegmental nucleus on neuronal activity in the rat lateral geniculate nucleus

1986 ◽  
Vol 56 (5) ◽  
pp. 1297-1309 ◽  
Author(s):  
Y. Kayama ◽  
M. Takagi ◽  
T. Ogawa
Keyword(s):  
Brain Stem ◽  
Lateral Geniculate Nucleus ◽  
Cholinergic Neurons ◽  
Photic Stimulation ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Laterodorsal Tegmental Nucleus ◽  
Tegmental Nucleus ◽  
Lateral Geniculate ◽  
Stimulation Of ◽  
Relay Neurons

The effect of stimulation of the laterodorsal tegmental nucleus (LDT) on the activity of single neurons in the dorsal lateral geniculate nucleus was studied in rats anesthetized with urethan. The LDT is the largest aggregation of cholinergic neurons in the brain stem that project to the thalamus, and in the rat is sufficiently compact to permit its localized stimulation. Position of stimulating electrodes was confirmed on histological sections processed with NADPH-diaphorase histochemistry, which in the rat brain stem selectively stains cholinergic neurons. Repetitive stimulation of the LDT at 200 Hz increased the firing rate of substantially all geniculate relay neurons and weakly depressed the activity of intrinsic interneurons. These effects usually occurred within several hundred milliseconds after the onset of stimulation and began to fade within a few seconds, despite continuing stimulation. The excitatory effects on relay neurons were blocked by scopolamine applied ionophoretically or intravenously, but not by noradrenergic antagonists, suggesting the cholinergic nature of LDT-induced excitation. During LDT stimulation the number of spikes evoked by photic stimulation of the receptive field of relay neurons usually increased, but it remained unchanged in a few cases. The increase was due to simple enhancement of photic responses or due to conversion of phasic type responses to tonic ones. As to the balance of background activity and photic responses, the effects of LDT stimulation varied from neuron to neuron. Even in a given neuron, the effects varied depending on its excitability level or the nature of the photic stimulation. These results show that the cholinergic projection from the LDT may be involved in the ascending reticular activating system, although the functional significance of the activating system in visual information processing in the geniculate nucleus remains to be clarified.

Quantitative age-related changes in dorsal lateral geniculate nucleus relay neurons of the rat

2004 ◽  
Vol 48 (4) ◽  
pp. 387-396 ◽  
Author(s):  
Lourdes Vidal ◽  
Concepción Ruı́z ◽  
Alicia Villena ◽  
Florentina Dı́az ◽  
Ignacio Pérez de Vargas
Keyword(s):  
Lateral Geniculate Nucleus ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Lateral Geniculate ◽  
Age Related ◽  
Dorsal Lateral Geniculate ◽  
Age Related Changes ◽  
Relay Neurons

Neonatal monocular enucleation and the geniculo-cortical system in the golden hamster: Shrinkage in dorsal lateral geniculate nucleus and area 17 and the effects on relay cell size and number

1995 ◽  
Vol 12 (5) ◽  
pp. 971-983 ◽  
Author(s):  
A.J. Trevelyan ◽  
I.D. Thompson
Keyword(s):  
Cell Size ◽  
Lateral Geniculate Nucleus ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Area 17 ◽  
Relay Cell ◽  
Monocular Enucleation ◽  
Lateral Geniculate ◽  
Retinal Input ◽  
Dorsal Lateral Geniculate ◽  
Relay Neurons

AbstractWe have examined the effects of neonatal monocular enucleation on the volume of the dorsal lateral geniculate nucleus (dLGN), the area of area 17, and the size and numbers of geniculate relay neurons identified by retrograde transport of HRP from cortex. Compared to values for normal animals, the only significant change contralateral to the remaining eye was an increase in relay cell radius. The effects ipsilateral to the remaining eye were more widespread: we found significant reductions in the volume of the dLGN (27% reduction), the area of striate cortex (22%), and the number (16%) and average soma radius (6%) of geniculate relay neurons. The relay neurons were also more densely packed, suggesting that other geniculate cell types were affected similarly, although this was not explicitly examined. These changes were not uniform throughout the nucleus, and as such, reflected the changes in retinal input. The greatest reduction in cell size occurred in the region of the ipsilateral dLGN receiving the most sparse retinal input subsequent to enucleation. Nor was the shrinkage of the dLGN uniform, being most apparent in the coronal plane especially along the axis orthogonal to the pia; there appeared to be little change in the anteroposterior extent. Shrinkage in area 17 ipsilateral to the remaining eye was the same (about 22%) whether it was defined by myelin staining or transneuronal transport of WGA-HRP. These results show that the transneuronal changes seen in the organization of visual cortex after early monocular enucleation in rodents are associated with only a moderate loss of geniculate relay cells.

scholarly journals Manifold learning analysis suggests strategies to align single-cell multimodal data of neuronal electrophysiology and transcriptomics

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jiawei Huang ◽  
Jie Sheng ◽  
Daifeng Wang
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Manifold Learning ◽  
Molecular Mechanisms ◽  
Single Cells ◽  
Cell Types ◽  
Functional Enrichment ◽  
Multimodal Data ◽  
Network Analyses ◽  
Manifold Alignment

AbstractRecent single-cell multimodal data reveal multi-scale characteristics of single cells, such as transcriptomics, morphology, and electrophysiology. However, integrating and analyzing such multimodal data to deeper understand functional genomics and gene regulation in various cellular characteristics remains elusive. To address this, we applied and benchmarked multiple machine learning methods to align gene expression and electrophysiological data of single neuronal cells in the mouse brain from the Brain Initiative. We found that nonlinear manifold learning outperforms other methods. After manifold alignment, the cells form clusters highly corresponding to transcriptomic and morphological cell types, suggesting a strong nonlinear relationship between gene expression and electrophysiology at the cell-type level. Also, the electrophysiological features are highly predictable by gene expression on the latent space from manifold alignment. The aligned cells further show continuous changes of electrophysiological features, implying cross-cluster gene expression transitions. Functional enrichment and gene regulatory network analyses for those cell clusters revealed potential genome functions and molecular mechanisms from gene expression to neuronal electrophysiology.

Laminar organization of tree shrew dorsal lateral geniculate nucleus

1983 ◽  
Vol 50 (6) ◽  
pp. 1330-1342 ◽  
Author(s):  
J. L. Conway ◽  
P. H. Schiller
Keyword(s):  
Lateral Geniculate Nucleus ◽  
Tree Shrew ◽  
Visual Stimuli ◽  
Optic Tract ◽  
Cell Types ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Lateral Geniculate ◽  
Tupaia Glis ◽  
Dorsal Lateral Geniculate ◽  
Laminar Specificity

This study investigated the organization of the dorsal lateral geniculate nucleus (LGN) of the tree shrew (Tupaia glis) using both microelectrode recording and anatomical techniques. The tree shrew LGN contains approximately 100,000 cells, of which 20% are in layers 2 and 6. These two layers receive input from the ipsilateral eye. The topography of the tree shrew LGN was delineated by taking systematic penetrations through the structure. Examination of the organization of the LGN laminae showed the following: in layer 1 (the lamina next to the optic tract) a mixture of on-center, off-center and on-off center cells was found; the majority of these cells responded transiently to visual stimuli and they had slightly longer conduction latencies than did cells in the other laminae. On-center and off-center cells in laminae 2-6 were sharply segregated: layers 2, 3, and 4 contained off-center cells and layers 5 and 6 contained on-center cells. Most of the cells in laminae 2-6 responded in a sustained manner to visual stimuli. These results suggest that one function of the LGN lamina is to group cells into various classes. Such grouping has now been shown to occur partially or completely for 1) eye of origin, 2) cell types characterized as on-center and off-center, and 3) cell types characterized as producing transient and sustained responses. The nature and degree of laminar specificity, however, varies considerably from species to species.

Sign in / Sign up

Export Citation Format

Share Document