scholarly journals Topographic connectivity and cellular profiling reveal detailed input pathways and functionally distinct cell types in the subthalamic nucleus

2021 ◽  
Author(s):  
Hyungju Jeon ◽  
Hojin Lee ◽  
Dae-Hyuk Kwon ◽  
Jiwon Kim ◽  
Keiko Tanaka-Yamamoto ◽  
...  
Keyword(s):  
Subthalamic Nucleus ◽  
Information Integration ◽  
Movement Control ◽  
Cell Types ◽  
Cellular Level ◽  
Input Circuit ◽  
Therapeutic Effects ◽  
Psychomotor Activity ◽  
Topographical Distribution ◽  
Detailed Circuit

SummaryThe subthalamic nucleus (STN) controls psychomotor activity and is an efficient therapeutic deep brain stimulation target in Parkinson’s disease patients. Despite evidence indicating position-dependent therapeutic effects and distinct functions within the STN, input circuit and cellular profile in the STN remain largely unclear. Using advanced neuroanatomical techniques, we constructed a comprehensive connectivity map of the indirect and hyperdirect pathways in both the mouse and human STN. Our detailed circuit- and cellular-level connectivity revealed a topographically graded organization with three convergent types of indirect and hyperdirect-pathways. Furthermore, we identified two functional types of glutamatergic STN neurons (parvalbumin, PV +/- neurons) segregated with a topographical distribution. Glutamatergic PV+ STN neurons contribute to burst firing. We confirmed synaptic connectivity from indirect and hyperdirect pathways to both PV+ and PV-. These data suggest a complex interplay of information integration within the basal ganglia underlying coordinated movement control and therapeutic effects.

scholarly journals Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution

2020 ◽  
Vol 22 (1) ◽  
pp. 261
Author(s):  
Abdelnaby Khalyfa ◽  
Wesley Warren ◽  
Jorge Andrade ◽  
Christopher A. Bottoms ◽  
Edward S. Rice ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Cell Types ◽  
Cellular Level ◽  
Cellular Heterogeneity ◽  
Transcriptional Networks ◽  
Metabolic Dysfunction ◽  
Rna Seq ◽  
Obstructive Sleep ◽  
Differential Expressed Gene ◽  
Key Aspects

Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA) and induces metabolic dysfunction manifesting as inflammation, increased lipolysis and insulin resistance in visceral white adipose tissues (vWAT). However, the cell types and their corresponding transcriptional pathways underlying these functional perturbations are unknown. Here, we applied single nucleus RNA sequencing (snRNA-seq) coupled with aggregate RNA-seq methods to evaluate the cellular heterogeneity in vWAT following IH exposures mimicking OSA. C57BL/6 male mice were exposed to IH and room air (RA) for 6 weeks, and nuclei from vWAT were isolated and processed for snRNA-seq followed by differential expressed gene (DEGs) analyses by cell type, along with gene ontology and canonical pathways enrichment tests of significance. IH induced significant transcriptional changes compared to RA across 14 different cell types identified in vWAT. We identified cell-specific signature markers, transcriptional networks, metabolic signaling pathways, and cellular subpopulation enrichment in vWAT. Globally, we also identify 298 common regulated genes across multiple cellular types that are associated with metabolic pathways. Deconvolution of cell types in vWAT using global RNA-seq revealed that distinct adipocytes appear to be differentially implicated in key aspects of metabolic dysfunction. Thus, the heterogeneity of vWAT and its response to IH at the cellular level provides important insights into the metabolic morbidity of OSA and may possibly translate into therapeutic targets.

Action and localization of acetylcholine in the cat retina

1987 ◽  
Vol 58 (5) ◽  
pp. 997-1015 ◽  
Author(s):  
M. Schmidt ◽  
M. F. Humphrey ◽  
H. Wassle
Keyword(s):  
Ganglion Cell ◽  
Amacrine Cells ◽  
Cell Types ◽  
Functional Independence ◽  
Dendritic Morphology ◽  
Immunocytochemical Staining ◽  
Simultaneous Application ◽  
Cat Retina ◽  
Topographical Distribution ◽  
Cholinergic Amacrine Cells

1. Retinal ganglion cells were recorded extracellularly in the intact eye of anesthetized adult cats. The effects of acetylcholine (ACh), the muscarinic antagonist scopolamine (Sco), the nicotinic antagonist dihydro-beta-erythroidine (DBE), and the acetylcholinesterase inhibitor physostigmine (Phy) on maintained and light-evoked ganglion cell discharge was examined using iontophoresis techniques. 2. A monoclonal antibody directed against the ACh synthesizing enzyme choline acetyltransferase (ChAT) was used to label cholinergic cells in retinal wholemounts. The topographical distribution of these cells was studied. 3. Intracellular filling with the fluorescent dye lucifer yellow (LY) was performed to identify the dendritic morphology of putative cholinergic neurons. 4. ACh increased and Sco decreased neuronal activity of all brisk ganglion cell types under all stimulus conditions tested in this study. The action of ACh was abolished during simultaneous application of Sco. 5. DBE raised the firing rate of ON-center brisk cells and decreased activity of OFF-center brisk cells. Again there was no difference under different stimulus conditions. During DBE application the ACh action on OFF-center cells was completely blocked. The ACh action on ON-center cells was diminished. 6. Phy prolonged and enhanced ACh action on all ganglion cell types. During simultaneous stimulation of the receptive-field center and the surround, Phy caused an activity shift in favor of the center response. 7. Immunocytochemical staining revealed two populations of amacrine cells, one in the inner nuclear layer, and the other in the ganglion cell layer. Their total density increased from 250 cells/mm2 in the periphery to 2,700 cells/mm2 in the central area. Analysis of the distribution pattern indicated a functional independence of the two subpopulations. 8. The dendritic morphology of putative cholinergic amacrine cells in the cat retina resembled that of rabbit and rat "starburst" amacrines, which are known to be cholinergic. 9. The possible function of cholinergic amacrine cells in the cat retina is discussed in view of the present findings and compared with results from other mammalian species.

scholarly journals A selective projection from the subthalamic nucleus to parvalbumin-expressing interneurons of the striatum

2020 ◽  
Author(s):  
Krishnakanth Kondabolu ◽  
Natalie M. Doig ◽  
Olaoluwa Ayeko ◽  
Bakhtawer Khan ◽  
Alexandra Torres ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Subthalamic Nucleus ◽  
Ex Vivo ◽  
Cell Types ◽  
Projection Neurons ◽  
Striatal Neurons ◽  
Primary Input ◽  
Cholinergic Interneurons ◽  
Axonal Connections ◽  
Excitatory Responses

AbstractThe striatum and subthalamic nucleus (STN) are considered to be the primary input nuclei of the basal ganglia. Projection neurons of both striatum and STN can extensively interact with other basal ganglia nuclei, and there is growing anatomical evidence of direct axonal connections from the STN to striatum. There remains, however, a pressing need to elucidate the organization and impact of these subthalamostriatal projections in the context of the diverse cell types constituting the striatum. To address this, we carried out monosynaptic retrograde tracing from genetically-defined populations of dorsal striatal neurons in adult male and female mice, quantifying the connectivity from STN neurons to spiny projection neurons, GABAergic interneurons, and cholinergic interneurons. In parallel, we used a combination of ex vivo electrophysiology and optogenetics to characterize the responses of a complementary range of dorsal striatal neuron types to activation of STN axons. Our tracing studies showed that the connectivity from STN neurons to striatal parvalbumin-expressing interneurons is significantly higher (~ four-to eight-fold) than that from STN to any of the four other striatal cell types examined. In agreement, our recording experiments showed that parvalbumin-expressing interneurons, but not the other cell types tested, commonly exhibited robust monosynaptic excitatory responses to subthalamostriatal inputs. Taken together, our data collectively demonstrate that the subthalamostriatal projection is highly selective for target cell type. We conclude that glutamatergic STN neurons are positioned to directly and powerfully influence striatal activity dynamics by virtue of their enriched innervation of GABAergic parvalbumin-expressing interneurons.

scholarly journals Cellular, molecular, and therapeutic characterization of pilocarpine-induced temporal lobe epilepsy.

2021 ◽  
Author(s):  
Rammohan Shukla ◽  
Nicholas D Henkel ◽  
Marissa A Smail ◽  
Xiaojun Wu ◽  
Heather A Enright ◽  
...  
Keyword(s):  
Machine Learning ◽  
Bayesian Inference ◽  
Pyramidal Neurons ◽  
Predictive Biomarkers ◽  
Cell Types ◽  
Cellular Level ◽  
Hippocampal Subfields ◽  
Synaptic Changes ◽  
Discovery Method

We probed a transcriptomic dataset of pilocarpine-induced TLE using various ontological, machine-learning, and systems-biology approaches. We showed that, underneath the complex and penetrant changes, moderate-to-subtle upregulated homeostatic and downregulated synaptic changes associated with the dentate gyrus and hippocampal subfields could not only predict TLE but various other forms of epilepsy. At the cellular level, pyramidal neurons and interneurons showed disparate changes, whereas the proportion of non-neuronal cells increased steadily. A probabilistic Bayesian network demonstrated an aberrant and oscillating physiological interaction between oligodendrocytes and interneurons in driving seizures. Validating the Bayesian inference, we showed that the cell types driving the seizures were associated with known antiepileptic and epileptic drugs. These findings provide predictive biomarkers of epilepsy, insights into the cellular connections and causal changes associated with TLE, and a drug discovery method focusing on these events.

scholarly journals Water contaminated with Didymosphenia geminata alters fish cell line viability

2018 ◽  
Author(s):  
Pamela Olivares ◽  
Matias Peredo-Parada ◽  
Viviana Chavez ◽  
Erico Carmona ◽  
Allison Astuya ◽  
...  
Keyword(s):  
River System ◽  
Cell Types ◽  
Complex Problem ◽  
Cellular Level ◽  
Lower Sensitivity ◽  
Fish Cell ◽  
Fish Cell Lines ◽  
Didymosphenia Geminata ◽  
Chronic Effects ◽  
The Moment

Didymosphenia geminata (D. geminata) in Chilean rivers is a complex problem. Its biology and effects on ecosystems is still being studied, at the moment not research has focused on its D. geminata effects at the cellular level. We developed an artificial river system to maintain D. geminata study material and evaluate effects of water contaminated with this diatom on the viability of two fish cell lines. Results indicate that CHSE-214 cells are sensitive to increasing D. geminata extract concentrations, reducing crop viability by 50% when exposed for 24 hours at a 0.01V/V dilution and reducing proliferative capacity by 70% on a 5 day temporal curve. SHK-1 cells showed lower sensitivity, presenting a decrease of 20% in viability at 24 hours, and a lower cell proliferation rate by day 5, but higher than of the CHSE-214 cells. Both lines were affected by exposure to D. geminata extracts, but CHSE-214 lines were more sensitive to polyphenols extracted from the microalgae. We conclude that certain cell types are sensitive to D. geminata in rivers, meaning that chronic effects on aquatic species contaminated with this diatom should be observed. Effects of this plague at a cellular level can be further studied to understand its full impact on river ecosystems.

scholarly journals Spatial-ATAC-seq: spatially resolved chromatin accessibility profiling of tissues at genome scale and cellular level

2021 ◽  
Author(s):  
Yanxiang Deng ◽  
Marek Bartosovic ◽  
Sai Ma ◽  
Di Zhang ◽  
Yang Liu ◽  
...  
Keyword(s):  
Immune Cell ◽  
System Development ◽  
Local Environment ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Cellular Level ◽  
Human Tonsil ◽  
Spatially Resolved ◽  
Fate Decision ◽  
Genome Scale

Cellular function in tissue is dependent upon the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context. The emergence of spatial transcriptomics has enabled genome-scale gene expression mapping, but it remains elusive to capture spatial epigenetic information of tissue at cellular level and genome scale. Here we report on spatial-ATAC-seq: spatially resolved chromatin accessibility profiling of tissue section via next-generation sequencing by combining in situ Tn5 transposition chemistry and microfluidic deterministic barcoding. Spatial chromatin accessibility profiling of mouse embryos delineated tissue region-specific epigenetic landscapes and identified gene regulators implicated in the central nerve system development. Mapping the accessible genome in human tonsil tissue with 20μm pixel size revealed spatially distinct organization of immune cell types and states in lymphoid follicles and extrafollicular zones. This technology takes spatial biology to a new realm by enabling spatially resolved epigenomics to improve our understanding of cell identity, state, and fate decision in relation to epigenetic underpinnings in development and disease.

scholarly journals Intraoperative Characterization of Subthalamic Nucleus-to-Cortex Evoked Potentials in Parkinson’s Disease Deep Brain Stimulation

2021 ◽  
Vol 15 ◽  
Author(s):  
Lila H. Levinson ◽  
David J. Caldwell ◽  
Jeneva A. Cronin ◽  
Brady Houston ◽  
Steve I. Perlmutter ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Evoked Potentials ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
High Frequency ◽  
Therapeutic Effects ◽  
Stn Dbs ◽  
Deep Brain

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson’s disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude (p < 0.05) and latency (p < 0.001), and the end, but not the start, EP magnitude has a significant relationship (p < 0.001, adjusted for random effects of subject) to ongoing high gamma (80–150 Hz) power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs.

Interactions between Neisseria meningitidis and human cells that promote colonisation and disease

2004 ◽  
Vol 6 (14) ◽  
pp. 1-14 ◽  
Author(s):  
Anne Corbett ◽  
Rachel Exley ◽  
Sandrine Bourdoulous ◽  
Christoph M. Tang
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Neisseria Meningitidis ◽  
Human Cell ◽  
Molecular Basis ◽  
Cell Types ◽  
Cellular Level ◽  
Human Cells ◽  
Healthy Individuals ◽  
Host Pathogen

Neisseria meningitidis is the leading cause of bacterial meningitis, a potentially fatal condition that particularly affects children. Multiple steps are involved during the pathogenesis of infection, including the colonisation of healthy individuals and invasion of the bacterium into the cerebrospinal fluid. The bacterium is capable of adhering to, and entering into, a range of human cell types, which facilitates its ability to cause disease. This article summarises the molecular basis of host–pathogen interactions at the cellular level during meningococcal carriage and disease.

Comparative analysis of expression profiles of chemokines, chemokine receptors, and components of signaling pathways mediated by chemokines in eight cell types during rat liver regeneration

Genome ◽  
2010 ◽  
Vol 53 (8) ◽  
pp. 608-618 ◽  
Author(s):  
Xiaoguang Chen ◽  
Cunshuan Xu ◽  
Fuchun Zhang ◽  
Ji Ma
Keyword(s):  
Liver Regeneration ◽  
Signaling Pathways ◽  
Expression Profiles ◽  
Gradient Centrifugation ◽  
Cell Types ◽  
Cellular Level ◽  
Pcr Analysis ◽  
Immunomagnetic Bead ◽  
Percoll Density Gradient Centrifugation ◽  
Chemokine Signaling

It has been documented that chemokines can positively regulate liver regeneration at the tissue level after partial hepatectomy. However, the precise mechanism of the effects of chemokines on regeneration at the cellular level remains poorly defined. In this study, 8 cell types from rat regenerating liver at 8 recovery time points after 2/3 hepatectomy were isolated and purified using Percoll density gradient centrifugation and immunomagnetic bead methods. The expression profiles of each cell type were monitored using a microarray. RT-PCR analysis was performed to validate the reliability of the microarray results. The results showed that, on the whole, the expression profiles of chemokine and receptor genes varied among different cell types; most genes involved in chemokine signaling pathways showed an increase in expression across the 8 liver cell types during liver regeneration. The implication of these genes in regeneration was analyzed by bioinformatics and systems biology methods. According to the microarray results and gene synergy, activation of chemokine signaling pathways at 24 h in biliary epithelial cells and at 2–12 h in dendritic cells may be triggered by CCL2–CCR2 and CCL7–CCR3, respectively; activation of Plc/Pkc and Pi3k/Akt pathways at 2–12 h in sinusoidal endothelial cells might be caused by CCL7–CCR1; and activation of the Src/Ptk, Src/Vav, and Plc/Pkc pathways at the priming stage may be related to the inductive effect of CCL7. These data suggest the potential relevance of the pro-inflammatory chemokines for liver regeneration at the cellular level.

Neuroanatomy and neurophysiology

2021 ◽  
pp. 725-852
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cervical Vertebrae ◽  
Lymphatic Vessels ◽  
Cell Types ◽  
Cellular Level ◽  
Inhibitory Synapses ◽  
The Central Nervous System ◽  
Emotion Memory ◽  
Different Cell Types

‘Neuroanatomy and neurophysiology’ covers the anatomy and organization of the central nervous system, including the skull and cervical vertebrae, the meninges, the blood and lymphatic vessels, muscles and nerves of the head and neck, and the structures of the eye, ear, and central nervous system. At a cellular level, the different cell types and the mechanism of transmission across synapses are considered, including excitatory and inhibitory synapses. This is followed by a review of the major control and sensory systems (including movement, information processing, locomotion, reflexes, and the main five senses of sight, hearing, touch, taste, and smell). The integration of these processes into higher functions (such as sleep, consciousness and coma, emotion, memory, and ageing) is discussed, along with the causes and treatments of disorders of diseases such as depression, schizophrenia, epilepsy, addiction, and degenerative diseases.

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