scholarly journals Conserved genetic signatures parcellate cardinal spinal neuron classes into local and projection subsets

Science ◽  
2021 ◽  
Vol 372 (6540) ◽  
pp. 385-393
Author(s):  
Peter J. Osseward ◽  
Neal D. Amin ◽  
Jeffrey D. Moore ◽  
Benjamin A. Temple ◽  
Bianca K. Barriga ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Long Range ◽  
Birth Date ◽  
Spinal Neuron ◽  
Top Down ◽  
Stepwise Manner ◽  
Neuronal Types ◽  
Genetic Signatures ◽  
Sensory Functions

Motor and sensory functions of the spinal cord are mediated by populations of cardinal neurons arising from separate progenitor lineages. However, each cardinal class is composed of multiple neuronal types with distinct molecular, anatomical, and physiological features, and there is not a unifying logic that systematically accounts for this diversity. We reasoned that the expansion of new neuronal types occurred in a stepwise manner analogous to animal speciation, and we explored this by defining transcriptomic relationships using a top-down approach. We uncovered orderly genetic tiers that sequentially divide groups of neurons by their motor-sensory, local-long range, and excitatory-inhibitory features. The genetic signatures defining neuronal projections were tied to neuronal birth date and conserved across cardinal classes. Thus, the intersection of cardinal class with projection markers provides a unifying taxonomic solution for systematically identifying distinct functional subsets.

scholarly journals Chimeric rabies SADB19-VSVg-pseudotyped lentiviral vectors mediate long-range retrograde transduction from the mouse spinal cord

Gene Therapy ◽  
2015 ◽  
Vol 22 (5) ◽  
pp. 357-364 ◽  
Author(s):  
L Schoderboeck ◽  
S Riad ◽  
A M Bokor ◽  
H E Wicky ◽  
M Strauss ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Long Range ◽  
Lentiviral Vectors ◽  
Mouse Spinal Cord

scholarly journals Selenium-Binding Protein 1 (SELENBP1) as Biomarker for Adverse Clinical Outcome After Traumatic Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Julian Seelig ◽  
Raban Arved Heller ◽  
Patrick Haubruck ◽  
Qian Sun ◽  
Jochen Georg Klingenberg ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Injury ◽  
Cell Damage ◽  
Cell Activity ◽  
Mechanical Trauma ◽  
Specific Cell ◽  
Traumatic Spinal Cord Injury ◽  
Cord Injury ◽  
Sensory Functions

Graphical AbstractThe pathophysiology of traumatic spinal cord injury (TSCI) can be divided into two major phases. (A) The mechanical trauma is followed within minutes by a secondary phase consisting of local complex and intertwined acute responses, intercellular signaling and cell activity regulating pathways. Inflammatory processes, oxidative stress and hypoxia, leading to cell damage and death, and specific cell contents are released into the circulation (B). The motor and sensory deficits upon TSCI are assessed by using the American Spinal Injury Association (ASIA) impairment scale (AIS), ranging from AIS A as a complete absence of any motor and sensory functions under the lesion site, to AIS E with complete preservation of motor and sensory functions. (C) The concentrations of serum SELENBP1 were elevated in patients classified as AIS A as compared to less severely affected patients classified as AIS B, C or D. A cut-off was deduced [(SELENBP1) > 30.2 μg/L], reliably predicting whether a patient belongs to the group showing neurological recovery (G1) or not (G0) within 3 months after the trauma. The figure was created by using https://biorender.com.

scholarly journals Spinal neuron-glia-immune interaction in cross-organ sensitization

2020 ◽  
Vol 319 (6) ◽  
pp. G748-G760
Author(s):  
Liya Y. Qiao ◽  
Namrata Tiwari
Keyword(s):  
Spinal Cord ◽  
Glial Cells ◽  
Sensory Information ◽  
Spinal Nerve ◽  
Primary Afferents ◽  
Leg Pain ◽  
Spinal Neuron ◽  
Afferent Neurons ◽  
Satellite Glial Cells ◽  
Integrative Processing

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), historically considered as regional gastrointestinal disorders with heightened colonic sensitivity, are increasingly recognized to have concurrent dysfunction of other visceral and somatic organs, such as urinary bladder hyperactivity, leg pain, and skin hypersensitivity. The interorgan sensory cross talk is, at large, termed “cross-organ sensitization.” These organs, anatomically distant from one another, physiologically interlock through projecting their sensory information into dorsal root ganglia (DRG) and then the spinal cord for integrative processing. The fundamental question of how sensitization of colonic afferent neurons conveys nociceptive information to activate primary afferents that innervate distant organs remains ambiguous. In DRG, primary afferent neurons are surrounded by satellite glial cells (SGCs) and macrophage accumulation in response to signals of injury to form a neuron-glia-macrophage triad. Astrocytes and microglia are major resident nonneuronal cells in the spinal cord to interact, physically and chemically, with sensory synapses. Cumulative evidence gathered so far indicate the indispensable roles of paracrine/autocrine interactions among neurons, glial cells, and immune cells in sensory cross-activation. Dichotomizing afferents, sensory convergency in the spinal cord, spinal nerve comingling, and extensive sprouting of central axons of primary afferents each has significant roles in the process of cross-organ sensitization; however, more results are required to explain their functional contributions. DRG that are located outside the blood-brain barrier and reside upstream in the cascade of sensory flow from one organ to the other in cross-organ sensitization could be safer therapeutic targets to produce less central adverse effects.

Different neuronal types in transneuronally WGA-HRP-labeled premotor interneurons of the rat spinal cord

1990 ◽  
Vol 38 (1) ◽  
pp. 77-81 ◽  
Author(s):  
Isabella Barajon ◽  
Laura Vizzotto ◽  
Giuliano Pizzini ◽  
Giovanni Tredici
Keyword(s):  
Spinal Cord ◽  
Rat Spinal Cord ◽  
Neuronal Types

Working Memory Processes Are Mediated by Local and Long-range Synchronization of Alpha Oscillations

2013 ◽  
Vol 25 (8) ◽  
pp. 1343-1357 ◽  
Author(s):  
Maite Crespo-Garcia ◽  
Diego Pinal ◽  
Jose L. Cantero ◽  
Fernando Díaz ◽  
Montserrat Zurrón ◽  
...  
Keyword(s):  
Working Memory ◽  
Long Range ◽  
Alpha Phase ◽  
Alpha Power ◽  
Phase Synchrony ◽  
Top Down ◽  
Alpha Oscillations ◽  
Memory Processes ◽  
Time Frequency ◽  
Cortical Regions

Different cortical dynamics of alpha oscillations (8–13 Hz) have been associated with increased working memory load, which have been mostly interpreted as a neural correlate of functional inhibition. This study aims at determining whether different manifestations of load-dependent amplitude and phase dynamics in the alpha band can coexist over different cortical regions. To address this question, we increased information load by manipulating the number and spatial configuration of domino spots. Time–frequency analysis of EEG source activity revealed (i) load-independent increases of both alpha power and interregional alpha-phase synchrony within task-irrelevant, posterior cortical regions and (ii) load-dependent decreases of alpha power over areas of the left pFC and bilateral posterior parietal cortex (PPC) preceded in time by load-dependent decreases of alpha-phase synchrony between the left pFC and the left PPC. The former results support the role of alpha oscillations in inhibiting irrelevant sensorimotor processing, whereas the latter likely reflect release of parietal task-relevant areas from top–down inhibition with load increase. This interpretation found further support in a significant latency shift of 15 msec from pFC to the PPC. Together, these results suggest that amplitude and phase alpha dynamics in both local and long-range cortical networks reflect different neural mechanisms of top–down control that might be crucial in mediating the different working memory processes.

scholarly journals Genetically identified spinal interneurons integrating tactile afferents for motor control

2015 ◽  
Vol 114 (6) ◽  
pp. 3050-3063 ◽  
Author(s):  
Tuan V. Bui ◽  
Nicolas Stifani ◽  
Izabela Panek ◽  
Carl Farah
Keyword(s):  
Spinal Cord ◽  
Motor Control ◽  
Sensory Information ◽  
Spinal Neuron ◽  
Spinal Neurons ◽  
Tactile Information ◽  
Spinal Interneurons ◽  
Motor Circuits ◽  
Neuron Populations ◽  
Genetic Techniques

Our movements are shaped by our perception of the world as communicated by our senses. Perception of sensory information has been largely attributed to cortical activity. However, a prior level of sensory processing occurs in the spinal cord. Indeed, sensory inputs directly project to many spinal circuits, some of which communicate with motor circuits within the spinal cord. Therefore, the processing of sensory information for the purpose of ensuring proper movements is distributed between spinal and supraspinal circuits. The mechanisms underlying the integration of sensory information for motor control at the level of the spinal cord have yet to be fully described. Recent research has led to the characterization of spinal neuron populations that share common molecular identities. Identification of molecular markers that define specific populations of spinal neurons is a prerequisite to the application of genetic techniques devised to both delineate the function of these spinal neurons and their connectivity. This strategy has been used in the study of spinal neurons that receive tactile inputs from sensory neurons innervating the skin. As a result, the circuits that include these spinal neurons have been revealed to play important roles in specific aspects of motor function. We describe these genetically identified spinal neurons that integrate tactile information and the contribution of these studies to our understanding of how tactile information shapes motor output. Furthermore, we describe future opportunities that these circuits present for shedding light on the neural mechanisms of tactile processing.

scholarly journals Inhibition of lncRNA H19/miR-370-3p pathway mitigates neuronal apoptosis in an in vitro model of spinal cord injury (SCI)

2021 ◽  
Vol 12 (1) ◽  
pp. 103-113
Author(s):  
Xin Li ◽  
Yan Qian ◽  
Kaihua Tang ◽  
Yang Li ◽  
Rui Tao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Caspase 3 ◽  
Quantitative Polymerase Chain Reaction ◽  
Inflammatory Factors ◽  
Spinal Neuron ◽  
Ros Generation ◽  
Cord Injury

Abstract Background Spinal cord injury (SCI) is the most serious complication of spinal injury, often leading to severe dysfunction of the limbs below the injured segment. Conventional therapy approaches are becoming less and less effective, and gene therapy is a new research direction by now. Methods The Sprague-Dawley rats were haphazardly assigned to two groups, namely sham group and SCI model group, and lncRNA H19 and miR-370-3p levels were investigated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Correlation between lncRNA H19 and miR-370-3p was ascertained by luciferase report assay and RT-qPCR. After transfection with si-H19, miR-370-3p inhibitor, negative controls (NC), or both, primary spinal neurons were subjected to the simulation of lipopolysaccharide (LPS) for inducing in vitro model of SCI. Cell viability, apoptotic rate, caspase-3 activity, Bax and Bcl-2 protein, ROS generation, TNF-α, IL-1β, and IL-6 protein, as well as IκBα and p65 phosphorylation ratio were evaluated adopting 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), apoptosis, caspase-3 activity, ROS generation, and western blot assays, thereby searching for the specific action mechanism on LPS-induced spinal never injury. Results SCI resulted in lncRNA H19 higher expression and miR-370-3p lower expression. LPS simulation raised a series of cellular biological changes, such as decreased viability, promoted apoptosis, generated ROS, and released inflammatory factors. lncRNA H19 inhibition reversed above LPS-induced changes. Besides, as the downstream target of lncRNA H19, miR-370-3p was oppositely regulated by lncRNA H19. The above biological changes induced by lncRNA H19 inhibition were reversed by miR-370-3p upregulation. Moreover, lncRNA H19 inhibition could block NF-κB pathway through miR-370-3p upregulation. Conclusion Inhibition of lncRNA H19/miR-370-3p mitigated spinal neuron apoptosis in an in vitro model of SCI. This provided the possibility for clinical use of gene therapy.

scholarly journals Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation

2021 ◽  
Vol 7 (10) ◽  
pp. eabe1527
Author(s):  
Elisa N. Falk ◽  
Kevin J. Norman ◽  
Yury Garkun ◽  
Michael P. Demars ◽  
Susanna Im ◽  
...  
Keyword(s):  
Long Range ◽  
Cognitive Deficits ◽  
Neurodevelopmental Disorders ◽  
Cholinergic System ◽  
Fragile X ◽  
Top Down ◽  
Dynamic Regulation ◽  
Key Driver ◽  
Maturational Process ◽  
Attentional Behavior

Cognitive function depends on frontal cortex development; however, the mechanisms driving this process are poorly understood. Here, we identify that dynamic regulation of the nicotinic cholinergic system is a key driver of attentional circuit maturation associated with top-down frontal neurons projecting to visual cortex. The top-down neurons receive robust cholinergic inputs, but their nicotinic tone decreases following adolescence by increasing expression of a nicotinic brake, Lynx1. Lynx1 shifts a balance between local and long-range inputs onto top-down frontal neurons following adolescence and promotes the establishment of attentional behavior in adulthood. This key maturational process is disrupted in a mouse model of fragile X syndrome but was rescued by a suppression of nicotinic tone through the introduction of Lynx1 in top-down projections. Nicotinic signaling may serve as a target to rebalance local/long-range balance and treat cognitive deficits in neurodevelopmental disorders.

Sign in / Sign up

Export Citation Format

Share Document