scholarly journals MicroRNAs mediate precise control of spinal interneuron populations to exert delicate sensory-to-motor outputs

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Shih-Hsin Chang ◽  
Yi-Ching Su ◽  
Mien Chang ◽  
Jun-An Chen
Keyword(s):  
Spinal Cord ◽  
Neural Circuit ◽  
Thermally Induced ◽  
Precise Control ◽  
Dynamic Expression ◽  
Spinal Interneuron ◽  
Motor Synergy ◽  
Response Thresholds ◽  
Fine Tune ◽  
Behavioral Assays

Although the function of microRNAs (miRNAs) during embryonic development has been intensively studied in recent years, their postnatal physiological functions remain largely unexplored due to inherent difficulties with the presence of redundant paralogs of the same seed. Thus, it is particularly challenging to uncover miRNA functions at neural circuit level since animal behaviors would need to be assessed upon complete loss of miRNA family functions. Here, we focused on the neural functions of MiR34/449 that manifests a dynamic expression pattern in the spinal cord from embryonic to postnatal stages. Our behavioral assays reveal that the loss of MiR34/449 miRNAs perturb thermally induced pain response thresholds and compromised delicate motor output in mice. Mechanistically, MiR34/449 directly target Satb1 and Satb2 to fine-tune the precise number of a sub-population of motor synergy encoder (MSE) neurons. Thus, MiR34/449 fine-tunes optimal development of Satb1/2on interneurons in the spinal cord, thereby refining explicit sensory-to-motor circuit outputs.

scholarly journals Oligodendrocyte Precursor Cells Sculpt the Visual System by Regulating Axonal Remodeling

2021 ◽  
Author(s):  
Yan Xiao ◽  
Laura J Hoodless ◽  
Luigi Petrucco ◽  
Ruben Portugues ◽  
Tim Czopka
Keyword(s):  
Neural Circuit ◽  
Precursor Cells ◽  
Retinal Ganglion ◽  
Oligodendrocyte Precursor Cells ◽  
Precise Control ◽  
Oligodendrocyte Precursor ◽  
Zebrafish Optic Tectum ◽  
And Function ◽  
Fine Tune ◽  
Ganglion Cell Axon

Many oligodendrocyte precursor cells (OPCs) do not differentiate to form myelin, suggesting additional roles of this cell population. The zebrafish optic tectum contains OPCs in regions devoid of myelin. Elimination of these OPCs impaired precise control of retinal ganglion cell axon arbor size during formation and maturation of retinotectal connectivity, and in consequence impaired visual acuity. Therefore, OPCs fine-tune neural circuit structure and function independently of their canonical role to make myelin.

Spinal cord representation of motor cortex plasticity reflects corticospinal tract LTP

2021 ◽  
Vol 118 (52) ◽  
pp. e2113192118
Author(s):  
Alzahraa Amer ◽  
Jianxun Xia ◽  
Michael Smith ◽  
John H. Martin
Keyword(s):  
Spinal Cord ◽  
Motor Cortex ◽  
Corticospinal Tract ◽  
Cervical Spinal Cord ◽  
Long Term Potentiation ◽  
Dependent Manner ◽  
Term Potentiation ◽  
Spinal Cord Segment ◽  
Spinal Interneuron ◽  
Activity Dependent

Although it is well known that activity-dependent motor cortex (MCX) plasticity produces long-term potentiation (LTP) of local cortical circuits, leading to enhanced muscle function, the effects on the corticospinal projection to spinal neurons has not yet been thoroughly studied. Here, we investigate a spinal locus for corticospinal tract (CST) plasticity in anesthetized rats using multichannel recording of motor-evoked, intraspinal local field potentials (LFPs) at the sixth cervical spinal cord segment. We produced LTP by intermittent theta burst electrical stimulation (iTBS) of the wrist area of MCX. Approximately 3 min of MCX iTBS potentiated the monosynaptic excitatory LFP recorded within the CST termination field in the dorsal horn and intermediate zone for at least 15 min after stimulation. Ventrolaterally, in the spinal cord gray matter, which is outside the CST termination field in rats, iTBS potentiated an oligosynaptic negative LFP that was localized to the wrist muscle motor pool. Spinal LTP remained robust, despite pharmacological blockade of iTBS-induced LTP within MCX using MK801, showing that activity-dependent spinal plasticity can be induced without concurrent MCX LTP. Pyramidal tract iTBS, which preferentially activates the CST, also produced significant spinal LTP, indicating the capacity for plasticity at the CST–spinal interneuron synapse. Our findings show CST monosynaptic LTP in spinal interneurons and demonstrate that spinal premotor circuits are capable of further modifying descending MCX control signals in an activity-dependent manner.

scholarly journals An In Vitro Protocol for Recording From Spinal Motoneurons of Adult Rats

2008 ◽  
Vol 100 (1) ◽  
pp. 474-481 ◽  
Author(s):  
Jonathan S. Carp ◽  
Ann M. Tennissen ◽  
Donna L. Mongeluzi ◽  
Christopher J. Dudek ◽  
Xiang Yang Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Action Potential ◽  
Mechanical Stability ◽  
Pharmacological Study ◽  
Input Resistance ◽  
Spinal Motoneurons ◽  
Adult Rats ◽  
Precise Control

In vitro slice preparations of CNS tissue are invaluable for studying neuronal function. However, up to now, slice protocols for adult mammal spinal motoneurons—the final common pathway for motor behaviors—have been available for only limited portions of the spinal cord. In most cases, these preparations have not been productive due to the poor viability of motoneurons in vitro. This report describes and validates a new slice protocol that for the first time provides reliable intracellular recordings from lumbar motoneurons of adult rats. The key features of this protocol are: preexposure to 100% oxygen; laminectomy prior to perfusion; anesthesia with ketamine/xylazine; embedding the spinal cord in agar prior to slicing; and, most important, brief incubation of spinal cord slices in a 30% solution of polyethylene glycol to promote resealing of the many motoneuron dendrites cut during sectioning. Together, these new features produce successful recordings in 76% of the experiments and an average action potential amplitude of 76 mV. Motoneuron properties measured in this new slice preparation (i.e., voltage and current thresholds for action potential initiation, input resistance, afterhyperpolarization size and duration, and onset and offset firing rates during current ramps) are comparable to those recorded in vivo. Given the mechanical stability and precise control over the extracellular environment afforded by an in vitro preparation, this new protocol can greatly facilitate electrophysiological and pharmacological study of these uniquely important neurons and other delicate neuronal populations in adult mammals.

scholarly journals Multiple Functions of Draxin/Netrin-1 Signaling in the Development of Neural Circuits in the Spinal Cord and the Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Giasuddin Ahmed ◽  
Yohei Shinmyo
Keyword(s):  
Spinal Cord ◽  
Axon Guidance ◽  
Neural Circuits ◽  
Neural Circuit ◽  
Deleted In Colorectal Cancer ◽  
Guidance Cue ◽  
Thalamocortical Projections ◽  
The Central Nervous System ◽  
Circuit Formation ◽  
The Brain

Axon guidance proteins play key roles in the formation of neural circuits during development. We previously identified an axon guidance cue, named draxin, that has no homology with other axon guidance proteins. Draxin is essential for the development of various neural circuits including the spinal cord commissure, corpus callosum, and thalamocortical projections. Draxin has been shown to not only control axon guidance through netrin-1 receptors, deleted in colorectal cancer (Dcc), and neogenin (Neo1) but also modulate netrin-1-mediated axon guidance and fasciculation. In this review, we summarize the multifaceted functions of draxin and netrin-1 signaling in neural circuit formation in the central nervous system. Furthermore, because recent studies suggest that the distributions and functions of axon guidance cues are highly regulated by glycoproteins such as Dystroglycan and Heparan sulfate proteoglycans, we discuss a possible function of glycoproteins in draxin/netrin-1-mediated axon guidance.

scholarly journals Nanoparticles in traumatic spinal cord injury: therapy and diagnosis

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 850
Author(s):  
Ahmed Hafez Mousa ◽  
Salwa Agha Mohammad ◽  
Hassan Mohammed Rezk ◽  
Khadijah Hassan Muzaffar ◽  
Asim Muhammed Alshanberi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Antimicrobial Agents ◽  
Spinal Cord Injuries ◽  
Industrial Applications ◽  
Precise Control ◽  
Drug Delivery Vehicles ◽  
Physico Chemical ◽  
Cord Injury ◽  
Biochemical Level ◽  
Therapy And Diagnosis

Nanotechnology has been previously employed for constructing drug delivery vehicles, biosensors, solar cells, lubricants and as antimicrobial agents. The advancement in synthesis procedure makes it possible to formulate nanoparticles (NPs) with precise control over physico-chemical and optical properties that are desired for specific clinical or biological applications. The surface modification technology has further added impetus to the specific applications of NPs by providing them with desirable characteristics. Hence, nanotechnology is of paramount importance in numerous biomedical and industrial applications due to their biocompatibility and stability even in harsh environments. Traumatic spinal cord injuries (TSCIs) are one of the major traumatic injuries that are commonly associated with severe consequences to the patient that may reach to the point of paralysis. Several processes occurring at a biochemical level which exacerbate the injury may be targeted using nanotechnology. This review discusses possible nanotechnology-based approaches for the diagnosis and therapy of TSCI, which have a bright future in clinical practice.

scholarly journals Hmx3a has essential functions in zebrafish spinal cord, ear and lateral line development

2020 ◽  
Author(s):  
Samantha J. England ◽  
Gustavo A. Cerda ◽  
Angelica Kowalchuk ◽  
Taylor Sorice ◽  
Ginny Grieb ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dna Binding ◽  
Embryonic Development ◽  
Lateral Line ◽  
Expression Patterns ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Spinal Cord Development ◽  
Spinal Interneuron ◽  
Sensory Structures

AbstractTranscription factors that contain a homeodomain DNA-binding domain have crucial functions in most aspects of cellular function and embryonic development in both animals and plants. Hmx proteins are a sub-family of NK homeodomain-containing proteins that have fundamental roles in development of sensory structures such as the eye and the ear. However, Hmx functions in spinal cord development have not been analyzed. Here we show that zebrafish (Danio rerio) hmx2 and hmx3a are co-expressed in spinal dI2 and V1 interneurons, whereas hmx3b, hmx1 and hmx4 are not expressed in spinal cord. Using mutational analyses, we demonstrate that, in addition to its previously reported role in ear development, hmx3a is required for correct specification of a subset of spinal interneuron neurotransmitter phenotypes, as well as correct lateral line progression and survival to adulthood. Surprisingly, despite similar expression patterns of hmx2 and hmx3a during embryonic development, zebrafish hmx2 mutants are viable and have no obviously abnormal phenotypes in sensory structures or neurons that require hmx3a. In addition, embryos homozygous for deletions of both hmx2 and hmx3a have identical phenotypes to severe hmx3a single mutants. However, mutating hmx2 in hypomorphic hmx3a mutants that usually develop normally, results in abnormal ear and lateral line phenotypes. This suggests that while hmx2 cannot compensate for loss of hmx3a, it does function in these developmental processes, although to a much lesser extent than hmx3a. More surprisingly, our mutational analyses suggest that Hmx3a may not require its homeodomain DNA-binding domain for its roles in viability or embryonic development.

scholarly journals Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Ying Wang ◽  
Wei Wu ◽  
Xiangbing Wu ◽  
Yan Sun ◽  
Yi P Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Targeted Delivery ◽  
Neural Circuit ◽  
Thoracic Spinal Cord ◽  
Spinal Cord Neurons ◽  
Thoracic Spinal ◽  
Virus Serotype ◽  
Cord Injury

Retrogradely-transported neurotrophin signaling plays an important role in regulating neural circuit specificity. Here we investigated whether targeted delivery of neurotrophin-3 (NT-3) to lumbar motoneurons (MNs) caudal to a thoracic (T10) contusive spinal cord injury (SCI) could modulate dendritic patterning and synapse formation of the lumbar MNs. In vitro, Adeno-associated virus serotype two overexpressing NT-3 (AAV-NT-3) induced NT-3 expression and neurite outgrowth in cultured spinal cord neurons. In vivo, targeted delivery of AAV-NT-3 into transiently demyelinated adult mouse sciatic nerves led to the retrograde transportation of NT-3 to the lumbar MNs, significantly attenuating SCI-induced lumbar MN dendritic atrophy. NT-3 enhanced sprouting and synaptic formation of descending serotonergic, dopaminergic, and propriospinal axons on lumbar MNs, parallel to improved behavioral recovery. Thus, retrogradely transported NT-3 stimulated remodeling of lumbar neural circuitry and synaptic connectivity remote to a thoracic SCI, supporting a role for retrograde transport of NT-3 as a potential therapeutic strategy for SCI.

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