scholarly journals Toward an integrated classification of neuronal cell types: morphoelectric and transcriptomic characterization of individual GABAergic cortical neurons

2020 ◽  
Author(s):  
Nathan W. Gouwens ◽  
Staci A. Sorensen ◽  
Fahimeh Baftizadeh ◽  
Agata Budzillo ◽  
Brian R. Lee ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Neuronal Cell ◽  
Cell Types ◽  
List Type ◽  
Physiological Properties ◽  
Cortical Interneurons ◽  
Definition Of ◽  
Visual Cortical ◽  
Mouse Visual Cortex

AbstractNeurons are frequently classified into distinct groups or cell types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 3,700 GABAergic mouse visual cortical neurons and reconstructed the local morphologies of 350 of those neurons. We found that most transcriptomic types (t-types) occupy specific laminar positions within mouse visual cortex, and many of those t-types exhibit consistent electrophysiological and morphological features. We observed that these properties could vary continuously between t-types, which limited the ability to predict specific t-types from other data modalities. Despite that, the data support the presence of at least 20 interneuron met-types that have congruent morphological, electrophysiological, and transcriptomic properties.HighlightsPatch-seq data obtained from >3,700 GABAergic cortical interneuronsComprehensive characterization of morpho-electric features of transcriptomic types20 interneuron met-types that have congruent properties across data modalitiesDifferent Sst met-types preferentially innervate different cortical layers

scholarly journals Electrophysiological and Transcriptomic Features Reveal a Circular Taxonomy of Cortical Neurons

2021 ◽  
Vol 15 ◽  
Author(s):  
Alejandro Rodríguez-Collado ◽  
Cristina Rueda
Keyword(s):  
Cortical Neurons ◽  
Cell Types ◽  
Mammalian Brain ◽  
Neuronal Dynamics ◽  
Electrophysiological Signals ◽  
Visual Cortex Neurons ◽  
Line Level ◽  
Mouse Visual Cortex ◽  
Different Levels

The complete understanding of the mammalian brain requires exact knowledge of the function of each neuron subpopulation composing its parts. To achieve this goal, an exhaustive, precise, reproducible, and robust neuronal taxonomy should be defined. In this paper, a new circular taxonomy based on transcriptomic features and novel electrophysiological features is proposed. The approach is validated by analysing more than 1850 electrophysiological signals of different mouse visual cortex neurons proceeding from the Allen Cell Types database. The study is conducted on two different levels: neurons and their cell-type aggregation into Cre lines. At the neuronal level, electrophysiological features have been extracted with a promising model that has already proved its worth in neuronal dynamics. At the Cre line level, electrophysiological and transcriptomic features are joined on cell types with available genetic information. A taxonomy with a circular order is revealed by a simple transformation of the first two principal components that allow the characterization of the different Cre lines. Moreover, the proposed methodology locates other Cre lines in the taxonomy that do not have transcriptomic features available. Finally, the taxonomy is validated by Machine Learning methods which are able to discriminate the different neuron types with the proposed electrophysiological features.

scholarly journals Electrophysiological and Transcriptomic Features Reveal a Circular Taxonomy of Cortical Neurons

2021 ◽  
Author(s):  
Alejandro Rodríguez-Collado ◽  
Cristina Rueda
Keyword(s):  
Cortical Neurons ◽  
Cell Types ◽  
Mammalian Brain ◽  
Neuronal Dynamics ◽  
Electrophysiological Signals ◽  
Visual Cortex Neurons ◽  
Line Level ◽  
Mouse Visual Cortex ◽  
Different Levels

The complete understanding of the mammalian brain requires exact knowledge of the function of each of the neurons composing its parts. To achieve this goal, an exhaustive, precise, reproducible, and robust neuronal taxonomy should be defined. In this paper, a new circular taxonomy based on transcriptomic features and novel electrophysiological features is proposed. The approach is validated by analysing more than 1850 electrophysiological signals of different mouse visual cortex neurons proceeding from the Allen Cell Types Database. The study is conducted on two different levels: neurons and their cell-type aggregation into Cre Lines. At the neuronal level, electrophysiological features have been extracted with a promising model that has already proved its worth in neuronal dynamics. At the Cre Line level, electrophysiological and transcriptomic features are joined on cell types with available genetic information. A taxonomy with a circular order is revealed by a simple transformation of the first two principal components that allow the characterization of the different Cre Lines. Moreover, the proposed methodology locates other Cre Lines in the taxonomy that do not have transcriptomic features available. Finally, the taxonomy is validated by Machine Learning methods which are able to discriminate the different neuron types with the proposed electrophysiological features.

scholarly journals Consistent cross-modal identification of cortical neurons with coupled autoencoders

2020 ◽  
Author(s):  
Rohan Gala ◽  
Agata Budzillo ◽  
Fahimeh Baftizadeh ◽  
Jeremy Miller ◽  
Nathan Gouwens ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Neuronal Cell ◽  
Cell Types ◽  
Modal Identification ◽  
Large Patch ◽  
Multimodal Data ◽  
Optimization Framework ◽  
Data Prediction ◽  
Cortical Interneurons ◽  
Assignment Analysis

AbstractConsistent identification of neurons and neuronal cell types across different observation modalities is an important problem in neuroscience. Here, we present an optimization framework to learn coordinated representations of multimodal data, and apply it to a large Patch-seq dataset of mouse cortical interneurons. Our approach reveals strong alignment between transcriptomic and electrophysiological profiles of neurons, enables accurate cross-modal data prediction, and identifies cell types that are consistent across modalities.HighlightsCoupled autoencoders for multimodal assignment, Analysis of Patch-seq data consisting of more than 3000 cells

scholarly journals 6B4 proteoglycan/phosphacan is a repulsive substratum but promotes morphological differentiation of cortical neurons

Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 647-658
Author(s):  
N. Maeda ◽  
M. Noda
Keyword(s):  
Cell Adhesion ◽  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Tyrosine Phosphatase ◽  
Neuronal Cell ◽  
Morphological Differentiation ◽  
Cell Types ◽  
Thalamic Neurons ◽  
Neurite Extension ◽  
The Brain

6B4 proteoglycan/phosphacan is one of the major phosphate-buffered saline-soluble chondroitin sulfate proteoglycans of the brain. Recently, this molecule has been demonstrated to be an extracellular variant of the proteoglycan-type protein tyrosine phosphatase, PTPzeta (RPTPbeta). The influence of the 6B4 proteoglycan, adsorbed onto the substratum, on cell adhesion and neurite outgrowth was studied using dissociated neurons from the cerebral cortex and thalamus. 6B4 proteoglycan adsorbed onto plastic tissue culture dishes did not support neuronal cell adhesion, but rather exerted repulsive effects on cortical and thalamic neurons. When neurons were densely seeded on patterned substrata consisting of a grid-like structure of alternating poly-L-lysine and 6B4 proteoglycan-coated poly-L-lysine domains, they were concentrated on the poly-L-lysine domains. However, 6B4 proteoglycan did not retard the differentiation of neurons but rather promoted neurite outgrowth and development of the dendrites of cortical neurons, when neurons were sparsely seeded on poly-L-lysine-conditioned coverslips continuously coated with 6B4 proteoglycan. This effect of 6B4 proteoglycan on the neurite extension of cortical neurons was apparent even on coverslips co-coated with fibronectin or tenascin. By contrast, the neurite extension of thalamic neurons was not modified by 6B4 proteoglycan. Chondroitinase ABC or keratanase digestion of 6B4 proteoglycan did not affect its neurite outgrowth promoting activity, but a polyclonal antibody against 6B4 proteoglycan completely suppressed this activity, suggesting that a protein moiety is responsible for the activity. 6B4 proteoglycan transiently promoted tyrosine phosphorylation of an 85x10(3) Mr protein in the cortical neurons, which correlated with the induction of neurite outgrowth. These results suggest that 6B4 proteoglycan/phosphacan modulates morphogenesis and differentiation of neurons dependent on its spatiotemporal distribution and the cell types in the brain.

Molecular characterization of neuronal cell types based on patterns of projection with Retro-TRAP

2015 ◽  
Vol 10 (9) ◽  
pp. 1319-1327 ◽  
Author(s):  
Alexander R Nectow ◽  
Mats I Ekstrand ◽  
Jeffrey M Friedman
Keyword(s):  
Molecular Characterization ◽  
Neuronal Cell ◽  
Cell Types

scholarly journals The fasciola cinereum of the hippocampus is important in the acquisition, but not the retrieval, of visual contextual memory

2019 ◽  
Author(s):  
Seong-Beom Park ◽  
Seung-Woo Yoo ◽  
Hyun-Suk Jung ◽  
Heung-Yeol Lim ◽  
Eunsoo Lee ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Cognitive Functions ◽  
Functional Significance ◽  
Contextual Memory ◽  
Anatomical Characteristics ◽  
Physiological Properties ◽  
Selective Ablation ◽  
Firing Properties ◽  
Definition Of

AbstractThe fasciola cinereum (FC) is a small subregion of the hippocampus that has been relatively unattended and less known compared with other subregions with respect to anatomical characteristics and functional significance. The lack of a detailed anatomical characterization of the FC has created ambiguity in the literature regarding the definition of FC borders with the CA1 subregion and attribution of cognitive functions to specific subregions of the hippocampus. Here, we show that the anatomical borders of the FC can be clearly defined histologically, and the region itself is characterized by unique anatomical connections and physiological properties. The major output of the FC is to the dentate gyrus (DG) and the FC itself. Firing properties of cells recorded from the FC were different from those in the CA1, and no sign of neurogenesis was detected in the FC. Selective ablation of neurons in the FC, successfully accomplished using colchicine, significantly impaired acquisition of novel visual-contextual memory in rats, without affecting retrieval of familiar visual-contextual memories. Our findings suggest that, given its connections to the DG, the FC may play critical roles in learning novel contextual behavior.

scholarly journals Recurrent interactions can explain the variance in single trial responses

2019 ◽  
Author(s):  
Subhodh Kotekal ◽  
Jason N. MacLean
Keyword(s):  
Functional Groups ◽  
Cortical Neurons ◽  
Sensory Information ◽  
Operational Definition ◽  
Single Trial ◽  
Running Speed ◽  
Local Correlations ◽  
Sensory Encoding ◽  
Definition Of ◽  
Visual Cortical

1.AbstractTo develop a complete description of sensory encoding, it is necessary to account for trial-to-trial variability in cortical neurons. Using a generalized linear model with terms corresponding to the visual stimulus, mouse running speed, and experimentally measured neuronal correlations, we modeled short term dynamics of L2/3 murine visual cortical neurons to evaluate the relative importance of each factor to neuronal variability within single trials. We find single trial predictions improve most when conditioning on the experimentally measured local correlations in comparison to predictions based on the stimulus or running speed. Specifically, accurate predictions are driven by positively co-varying and synchronously active functional groups of neurons. Including functional groups in the model enhances decoding accuracy of sensory information compared to a model that assumes neuronal independence. Functional groups, in encoding and decoding frameworks, provide an operational definition of Hebbian assemblies in which local correlations largely explain neuronal responses on individual trials.

scholarly journals Characterization of a subpopulation of developing cortical interneurons from human iPSCs within serum-free embryoid bodies

2015 ◽  
Vol 308 (3) ◽  
pp. C209-C219 ◽  
Author(s):  
Michael W. Nestor ◽  
Samson Jacob ◽  
Bruce Sun ◽  
Deborah Prè ◽  
Andrew A. Sproul ◽  
...  
Keyword(s):  
Pluripotent Stem Cells ◽  
Cell Sorting ◽  
Cortical Development ◽  
Neuronal Cell ◽  
Embryoid Bodies ◽  
Cell Type ◽  
Serum Free ◽  
Human Ipscs ◽  
Cortical Interneurons

Production and isolation of forebrain interneuron progenitors are essential for understanding cortical development and developing cell-based therapies for developmental and neurodegenerative disorders. We demonstrate production of a population of putative calretinin-positive bipolar interneurons that express markers consistent with caudal ganglionic eminence identities. Using serum-free embryoid bodies (SFEBs) generated from human inducible pluripotent stem cells (iPSCs), we demonstrate that these interneuron progenitors exhibit morphological, immunocytochemical, and electrophysiological hallmarks of developing cortical interneurons. Finally, we develop a fluorescence-activated cell-sorting strategy to isolate interneuron progenitors from SFEBs to allow development of a purified population of these cells. Identification of this critical neuronal cell type within iPSC-derived SFEBs is an important and novel step in describing cortical development in this iPSC preparation.

scholarly journals Layer-specific chromatin accessibility landscapes reveal regulatory networks in adult mouse visual cortex

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Lucas T Gray ◽  
Zizhen Yao ◽  
Thuc Nghi Nguyen ◽  
Tae Kyung Kim ◽  
Hongkui Zeng ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Regulatory Networks ◽  
High Throughput Sequencing ◽  
Adult Mouse ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Binding Motifs ◽  
Mouse Cortex ◽  
Mouse Visual Cortex

Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers. Integration of these data with layer-specific transcriptomic profiles and transcription factor binding motifs enabled us to construct a regulatory network revealing potential key layer-specific regulators, including Cux1/2, Foxp2, Nfia, Pou3f2, and Rorb. This dataset is a valuable resource for identifying candidate layer-specific cis-regulatory elements in adult mouse cortex.

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