scholarly journals Synaptic Variability Introduces State-Dependent Modulation of Excitatory Spinal Cord Synapses

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
David Parker
Keyword(s):  
Spinal Cord ◽  
Synaptic Plasticity ◽  
Motor Neurons ◽  
Low Frequency ◽  
Spike Trains ◽  
Release Probability ◽  
Vesicle Pools ◽  
State Dependent ◽  
Initial Release ◽  
Synaptic Variability

The relevance of neuronal and synaptic variability remains unclear. Cellular and synaptic plasticity and neuromodulation are also variable. This could reflect state-dependent effects caused by the variable initial cellular or synaptic properties or direct variability in plasticity-inducing mechanisms. This study has examined state-dependent influences on synaptic plasticity at connections between excitatory interneurons (EIN) and motor neurons in the lamprey spinal cord. State-dependent effects were examined by correlating initial synaptic properties with the substance P-mediated plasticity of low frequency-evoked EPSPs and the reduction of the EPSP depression over spike trains (metaplasticity). The low frequency EPSP potentiation reflected an interaction between the potentiation of NMDA responses and the release probability. The release probability introduced a variable state-dependent subtractive influence on the postsynaptic NMDA-dependent potentiation. The metaplasticity was also state-dependent: it was greater at connections with smaller available vesicle pools and high initial release probabilities. This was supported by the significant reduction in the number of connections showing metaplasticity when the release probability was reduced by high Mg2+Ringer. Initial synaptic properties thus introduce state-dependent influences that affect the potential for plasticity. Understanding these conditions will be as important as understanding the subsequent changes.

scholarly journals The Temporal Mechanisms Guiding Interneuron Differentiation in the Spinal Cord

2021 ◽  
Vol 22 (15) ◽  
pp. 8025
Author(s):  
Dylan Deska-Gauthier ◽  
Ying Zhang
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
The Other ◽  
Neuronal Diversity ◽  
Collective Knowledge ◽  
Mouse Spinal Cord ◽  
Developmental Mechanism ◽  
State Dependent ◽  
The Central Nervous System

Neurogenesis timing is an essential developmental mechanism for neuronal diversity and organization throughout the central nervous system. In the mouse spinal cord, growing evidence is beginning to reveal that neurogenesis timing acts in tandem with spatial molecular controls to diversify molecularly and functionally distinct post-mitotic interneuron subpopulations. Particularly, in some cases, this temporal ordering of interneuron differentiation has been shown to instruct specific sensorimotor circuit wirings. In zebrafish, in vivo preparations have revealed that sequential neurogenesis waves of interneurons and motor neurons form speed-dependent locomotor circuits throughout the spinal cord and brainstem. In the present review, we discuss temporal principals of interneuron diversity taken from both mouse and zebrafish systems highlighting how each can lend illuminating insights to the other. Moving forward, it is important to combine the collective knowledge from different systems to eventually understand how temporally regulated subpopulation function differentially across speed- and/or state-dependent sensorimotor movement tasks.

Modulation of Cellular and Synaptic Variability in the Lamprey Spinal Cord

2007 ◽  
Vol 97 (1) ◽  
pp. 44-56 ◽  
Author(s):  
David Parker ◽  
Sarah Bevan
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Motor Neurons ◽  
Network Activity ◽  
Inhibitory Interneurons ◽  
Additional Source ◽  
Mean Values ◽  
Different Types ◽  
Network Properties ◽  
Synaptic Variability

Variability is increasingly recognized as a characteristic feature of cellular, synaptic, and network properties. While studies have traditionally focused on mean values, significant effects can result from changes in variance. This study has examined cellular and synaptic variability in the lamprey spinal cord and its modulation by the neuropeptide substance P. Cellular and synaptic variability differed in different types of cell and synapse. Substance P reduced the variability of subthreshold locomotor-related depolarizations and spiking in motor neurons during network activity. These effects were associated with a reduction in the variability of spiking in glutamatergic excitatory network interneurons and with a reduction in the variance of excitatory interneuron-evoked excitatory postsynaptic potentials (EPSPs). Substance P also reduced the variance of postsynpatic potentials (PSPs) from crossing inhibitory and excitatory interneurons, but it increased the variance of inhibitory postsynpatic potentials (IPSPs) from ipsilateral inhibitory interneurons. The effects on the variance of different PSPs could occur with or without changes in the PSP amplitude. The reduction in the variance of excitatory interneuron-evoked EPSPs was protein kinase A, calcium, and N-methyl-d-aspartate (NMDA) dependent. The NMDA dependence suggested that substance P was acting postsynaptically. This was supported by the reduced variability of postsynaptic responses to glutamate by substance P. However, ultrastructural analyses suggested that there may also be a presynaptic component to the modulation, because substance P reduced the variability of synaptic vesicle diameters in putative glutamatergic terminals. These results suggest that cellular and synaptic variability can be targeted for modulation, making it an additional source of spinal cord plasticity.

Effects of HBO with reduction of iNOS and HIF -1α in motor neurons after transient spinal cord ischemia in rabbits

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S452-S452
Author(s):  
Noritaka Murakami ◽  
Masahiro Sakurai ◽  
Takashi Horinouchi ◽  
Jun Ito ◽  
Shin Kurosawa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Spinal Cord Ischemia

scholarly journals Restoration of breathing after opioid overdose and spinal cord injury using temporal interference stimulation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Michael D. Sunshine ◽  
Antonino M. Cassarà ◽  
Esra Neufeld ◽  
Nir Grossman ◽  
Thomas H. Mareci ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Drug Overdose ◽  
Cervical Spinal Cord ◽  
Opioid Overdose ◽  
Electrode Position ◽  
Spinal Motor Neurons ◽  
Cord Injury ◽  
Low Amplitude

AbstractRespiratory insufficiency is a leading cause of death due to drug overdose or neuromuscular disease. We hypothesized that a stimulation paradigm using temporal interference (TI) could restore breathing in such conditions. Following opioid overdose in rats, two high frequency (5000 Hz and 5001 Hz), low amplitude waveforms delivered via intramuscular wires in the neck immediately activated the diaphragm and restored ventilation in phase with waveform offset (1 Hz or 60 breaths/min). Following cervical spinal cord injury (SCI), TI stimulation via dorsally placed epidural electrodes uni- or bilaterally activated the diaphragm depending on current and electrode position. In silico modeling indicated that an interferential signal in the ventral spinal cord predicted the evoked response (left versus right diaphragm) and current-ratio-based steering. We conclude that TI stimulation can activate spinal motor neurons after SCI and prevent fatal apnea during drug overdose by restoring ventilation with minimally invasive electrodes.

scholarly journals Single-cell transcriptomic analysis of the adult mouse spinal cord reveals molecular diversity of autonomic and skeletal motor neurons

2021 ◽  
Vol 24 (4) ◽  
pp. 572-583 ◽  
Author(s):  
Jacob A. Blum ◽  
Sandy Klemm ◽  
Jennifer L. Shadrach ◽  
Kevin A. Guttenplan ◽  
Lisa Nakayama ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Single Cell ◽  
Motor Neurons ◽  
Molecular Diversity ◽  
Adult Mouse ◽  
Transcriptomic Analysis ◽  
Mouse Spinal Cord

scholarly journals CD157 in bone marrow mesenchymal stem cells mediates mitochondrial production and transfer to improve neuronal apoptosis and functional recovery after spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Li ◽  
Heyangzi Li ◽  
Simin Cai ◽  
Shi Bai ◽  
Huabo Cai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Neurons ◽  
Functional Recovery ◽  
Mitochondrial Transfer ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells

Abstract Background Recent studies demonstrated that autologous mitochondria derived from bone marrow mesenchymal stem cells (BMSCs) might be valuable in the treatment of spinal cord injury (SCI). However, the mechanisms of mitochondrial transfer from BMSCs to injured neurons are not fully understood. Methods We modified BMSCs by CD157, a cell surface molecule as a potential regulator mitochondria transfer, then transplanted to SCI rats and co-cultured with OGD injured VSC4.1 motor neuron. We detected extracellular mitochondrial particles derived from BMSCs by transmission electron microscope and measured the CD157/cyclic ADP-ribose signaling pathway-related protein expression by immunohistochemistry and Western blotting assay. The CD157 ADPR-cyclase activity and Fluo-4 AM was used to detect the Ca2+ signal. All data were expressed as mean ± SEM. Statistical analysis was analyzed by GraphPad Prism 6 software. Unpaired t-test was used for the analysis of two groups. Multiple comparisons were evaluated by one-way ANOVA or two-way ANOVA. Results CD157 on BMSCs was upregulated when co-cultured with injured VSC4.1 motor neurons. Upregulation of CD157 on BMSCs could raise the transfer extracellular mitochondria particles to VSC4.1 motor neurons, gradually regenerate the axon of VSC4.1 motor neuron and reduce the cell apoptosis. Transplantation of CD157-modified BMSCs at the injured sites could significantly improve the functional recovery, axon regeneration, and neuron apoptosis in SCI rats. The level of Ca2+ in CD157-modified BMSCs dramatically increased when objected to high concentration cADPR, ATP content, and MMP of BMSCs also increased. Conclusion The present results suggested that CD157 can regulate the production and transfer of BMSC-derived extracellular mitochondrial particles, enriching the mechanism of the extracellular mitochondrial transfer in BMSCs transplantation and providing a novel strategy to improve the stem cell treatment on SCI.

Muscle-conditioned media and cAMP promote survival and neurite outgrowth of adult spinal cord motor neurons

2009 ◽  
Vol 220 (2) ◽  
pp. 303-315 ◽  
Author(s):  
Jose V. Montoya G. ◽  
Jhon Jairo Sutachan ◽  
Wai Si Chan ◽  
Alexandra Sideris ◽  
Thomas J.J. Blanck ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neurite Outgrowth ◽  
Motor Neurons ◽  
Conditioned Media ◽  
Adult Spinal Cord

scholarly journals RBM45 Modulates the Antioxidant Response in Amyotrophic Lateral Sclerosis through Interactions with KEAP1

2015 ◽  
Vol 35 (14) ◽  
pp. 2385-2399 ◽  
Author(s):  
Nadine Bakkar ◽  
Arianna Kousari ◽  
Tina Kovalik ◽  
Yang Li ◽  
Robert Bowser
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Antioxidant Response ◽  
Cytoplasmic Inclusions ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective loss of motor neurons. Various factors contribute to the disease, including RNA binding protein dysregulation and oxidative stress, but their exact role in pathogenic mechanisms remains unclear. We have recently linked another RNA binding protein, RBM45, to ALS via increased levels of protein in the cerebrospinal fluid of ALS patients and its localization to cytoplasmic inclusions in ALS motor neurons. Here we show RBM45 nuclear exit in ALS spinal cord motor neurons compared to controls, a phenotype recapitulatedin vitroin motor neurons treated with oxidative stressors. We find that RBM45 binds and stabilizes KEAP1, the inhibitor of the antioxidant response transcription factor NRF2. ALS lumbar spinal cord lysates similarly show increased cytoplasmic binding of KEAP1 and RBM45. Binding of RBM45 to KEAP1 impedes the protective antioxidant response, thus contributing to oxidative stress-induced cellular toxicity. Our findings thus describe a novel link between a mislocalized RNA binding protein implicated in ALS (RBM45) and dysregulation of the neuroprotective antioxidant response seen in the disease.

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