scholarly journals Corticothalamic Pathways From Layer 5: Emerging Roles in Computation and Pathology

2021 ◽  
Vol 15 ◽  
Author(s):  
Rebecca A. Mease ◽  
Antonio J. Gonzalez
Keyword(s):  
Single Neuron ◽  
Brain Regions ◽  
Cortical Layer ◽  
Cell Type ◽  
First Order ◽  
Sensory Modalities ◽  
Important Pathway ◽  
Cell Type Specific ◽  
Computational Properties

Large portions of the thalamus receive strong driving input from cortical layer 5 (L5) neurons but the role of this important pathway in cortical and thalamic computations is not well understood. L5-recipient “higher-order” thalamic regions participate in cortico-thalamo-cortical (CTC) circuits that are increasingly recognized to be (1) anatomically and functionally distinct from better-studied “first-order” CTC networks, and (2) integral to cortical activity related to learning and perception. Additionally, studies are beginning to elucidate the clinical relevance of these networks, as dysfunction across these pathways have been implicated in several pathological states. In this review, we highlight recent advances in understanding L5 CTC networks across sensory modalities and brain regions, particularly studies leveraging cell-type-specific tools that allow precise experimental access to L5 CTC circuits. We aim to provide a focused and accessible summary of the anatomical, physiological, and computational properties of L5-originating CTC networks, and outline their underappreciated contribution in pathology. We particularly seek to connect single-neuron and synaptic properties to network (dys)function and emerging theories of cortical computation, and highlight information processing in L5 CTC networks as a promising focus for computational studies.

scholarly journals Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiao Li ◽  
Jakob Seidlitz ◽  
John Suckling ◽  
Feiyang Fan ◽  
Gong-Jun Ji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Structural Changes ◽  
Brain Regions ◽  
Cell Type ◽  
Major Depressive ◽  
Structural Differences ◽  
Neuroimaging Data ◽  
Cell Type Specific

AbstractMajor depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.

The role of CpG methylation in cell type-specific expression of the aquaporin-5 gene

2007 ◽  
Vol 353 (4) ◽  
pp. 1017-1022 ◽  
Author(s):  
Johji Nomura ◽  
Akinori Hisatsune ◽  
Takeshi Miyata ◽  
Yoichiro Isohama
Keyword(s):  
Cpg Methylation ◽  
Cell Type ◽  
Aquaporin 5 ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

scholarly journals Cell type-specific effects of isoflurane on two distinct afferent inputs to cortical layer 1

2020 ◽  
Author(s):  
Caitlin A. Murphy ◽  
Matthew I. Banks
Keyword(s):  
Ex Vivo ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Cellular Level ◽  
Cortical Layer ◽  
Cell Type ◽  
Specific Effects ◽  
Primary Mouse ◽  
Cell Type Specific ◽  
Synaptic Responses

ABSTRACTBackgroundWhile their behavioral effects are well-characterized, the mechanisms by which anaesthetics induce loss of consciousness are largely unknown. Anaesthetics may disrupt integration and propagation of information in corticothalamic networks. Recent studies have shown that isoflurane diminishes synaptic responses of thalamocortical (TC) and corticocortical (CC) afferents in a pathway-specific manner. However, whether the synaptic effects of isoflurane observed in extracellular recordings persist at the cellular level has yet to be explored.MethodsHere, we activate TC and CC layer 1 inputs in non-primary mouse neocortex in ex vivo brain slices and explore the degree to which isoflurane modulates synaptic responses in pyramidal cells and in two inhibitory cell populations, somatostatin-positive (SOM+) and parvalbumin-positive (PV+) interneurons.ResultsWe show that the effects of isoflurane on synaptic responses and intrinsic properties of these cells varies among cell type and by cortical layer. Layer 1 inputs to L4 pyramidal cells were suppressed by isoflurane at both TC and CC synapses, while those to L2/3 pyramidal cells and PV+ interneurons were not. TC inputs to SOM+ cells were rarely observed at all, while CC inputs to SOM+ interneurons were robustly suppressed by isoflurane.ConclusionsThese results suggest a mechanism by which isoflurane disrupts integration and propagation of thalamocortical and intracortical signals.

scholarly journals Cell-type specific innervation of cortical pyramidal cells at their apical dendrites

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ali Karimi ◽  
Jan Odenthal ◽  
Florian Drawitsch ◽  
Kevin M Boergens ◽  
Moritz Helmstaedter
Keyword(s):  
Electron Microscopy ◽  
Pyramidal Cells ◽  
Inhibitory Input ◽  
Cell Type ◽  
Cell Type Specific ◽  
Cortical Regions ◽  
Apical Dendrites ◽  
Computational Properties

We investigated the synaptic innervation of apical dendrites of cortical pyramidal cells in a region between layers (L) 1 and 2 using 3-D electron microscopy applied to four cortical regions in mouse. We found the relative inhibitory input at the apical dendrite’s main bifurcation to be more than 2-fold larger for L2 than L3 and L5 thick-tufted pyramidal cells. Towards the distal tuft dendrites in upper L1, the relative inhibitory input was at least about 2-fold larger for L5 pyramidal cells than for all others. Only L3 pyramidal cells showed homogeneous inhibitory input fraction. The inhibitory-to-excitatory synaptic ratio is thus specific for the types of pyramidal cells. Inhibitory axons preferentially innervated either L2 or L3/5 apical dendrites, but not both. These findings describe connectomic principles for the control of pyramidal cells at their apical dendrites and support differential computational properties of L2, L3 and subtypes of L5 pyramidal cells in cortex.

scholarly journals Target-specific M1 inputs to infragranular S1 pyramidal neurons

2016 ◽  
Vol 116 (3) ◽  
pp. 1261-1274 ◽  
Author(s):  
Amanda K. Kinnischtzke ◽  
Erika E. Fanselow ◽  
Daniel J. Simons
Keyword(s):  
Primary Motor Cortex ◽  
Pyramidal Neurons ◽  
Projection Neurons ◽  
Cell Type ◽  
Intrinsic Properties ◽  
Subcortical Structures ◽  
Medial Nucleus ◽  
Cell Type Specific ◽  
Posterior Medial Nucleus

The functional role of input from the primary motor cortex (M1) to primary somatosensory cortex (S1) is unclear; one key to understanding this pathway may lie in elucidating the cell-type specific microcircuits that connect S1 and M1. Recently, we discovered that a subset of pyramidal neurons in the infragranular layers of S1 receive especially strong input from M1 (Kinnischtzke AK, Simons DJ, Fanselow EE. Cereb Cortex 24: 2237–2248, 2014), suggesting that M1 may affect specific classes of pyramidal neurons differently. Here, using combined optogenetic and retrograde labeling approaches in the mouse, we examined the strengths of M1 inputs to five classes of infragranular S1 neurons categorized by their projections to particular cortical and subcortical targets. We found that the magnitude of M1 synaptic input to S1 pyramidal neurons varies greatly depending on the projection target of the postsynaptic neuron. Of the populations examined, M1-projecting corticocortical neurons in L6 received the strongest M1 inputs, whereas ventral posterior medial nucleus-projecting corticothalamic neurons, also located in L6, received the weakest. Each population also possessed distinct intrinsic properties. The results suggest that M1 differentially engages specific classes of S1 projection neurons, thereby regulating the motor-related influence S1 exerts over subcortical structures.

scholarly journals Conditional ablation and conditional rescue models for Casq2 elucidate the role of development and of cell-type specific expression of Casq2 in the CPVT2 phenotype

2018 ◽  
Vol 27 (9) ◽  
pp. 1533-1544 ◽  
Author(s):  
Daniel J Flores ◽  
ThuyVy Duong ◽  
Luke O Brandenberger ◽  
Apratim Mitra ◽  
Aditya Shirali ◽  
...  
Keyword(s):  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

scholarly journals Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice

2018 ◽  
Vol 115 (20) ◽  
pp. 5253-5258 ◽  
Author(s):  
Hideyuki Yanai ◽  
Shiho Chiba ◽  
Sho Hangai ◽  
Kohei Kometani ◽  
Asuka Inoue ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Types ◽  
Type I ◽  
Type I Ifn ◽  
Cell Type ◽  
Gene Ablation ◽  
Cell Type Specific

IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3’s broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3. Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4–IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.

scholarly journals Auxins and Cytokinins—The Role of Subcellular Organization on Homeostasis

2018 ◽  
Vol 19 (10) ◽  
pp. 3115 ◽  
Author(s):  
Vladimír Skalický ◽  
Martin Kubeš ◽  
Richard Napier ◽  
Ondřej Novák
Keyword(s):  
Plant Growth ◽  
Growth And Development ◽  
Recent Progress ◽  
Plant Hormone ◽  
Cell Type ◽  
Plant Growth And Development ◽  
Master Regulators ◽  
Cell Type Specific ◽  
Structural Levels

Plant hormones are master regulators of plant growth and development. Better knowledge of their spatial signaling and homeostasis (transport and metabolism) on the lowest structural levels (cellular and subcellular) is therefore crucial to a better understanding of developmental processes in plants. Recent progress in phytohormone analysis at the cellular and subcellular levels has greatly improved the effectiveness of isolation protocols and the sensitivity of analytical methods. This review is mainly focused on homeostasis of two plant hormone groups, auxins and cytokinins. It will summarize and discuss their tissue- and cell-type specific distributions at the cellular and subcellular levels.

scholarly journals Using multiple measurements of tissue to estimate subject- and cell-type-specific gene expression

2019 ◽  
Vol 36 (3) ◽  
pp. 782-788 ◽  
Author(s):  
Jiebiao Wang ◽  
Bernie Devlin ◽  
Kathryn Roeder
Keyword(s):  
Gene Expression ◽  
Empirical Bayes ◽  
Brain Regions ◽  
Tissue Level ◽  
Supplementary Information ◽  
Specific Gene ◽  
Expression Data ◽  
Cell Type ◽  
Multiple Measurements ◽  
Cell Type Specific

Abstract Motivation Patterns of gene expression, quantified at the level of tissue or cells, can inform on etiology of disease. There are now rich resources for tissue-level (bulk) gene expression data, which have been collected from thousands of subjects, and resources involving single-cell RNA-sequencing (scRNA-seq) data are expanding rapidly. The latter yields cell type information, although the data can be noisy and typically are derived from a small number of subjects. Results Complementing these approaches, we develop a method to estimate subject- and cell-type-specific (CTS) gene expression from tissue using an empirical Bayes method that borrows information across multiple measurements of the same tissue per subject (e.g. multiple regions of the brain). Analyzing expression data from multiple brain regions from the Genotype-Tissue Expression project (GTEx) reveals CTS expression, which then permits downstream analyses, such as identification of CTS expression Quantitative Trait Loci (eQTL). Availability and implementation We implement this method as an R package MIND, hosted on https://github.com/randel/MIND. Supplementary information Supplementary data are available at Bioinformatics online.

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