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https://www.readbyqxmd.com/read/28821650/feedback-signal-from-motoneurons-influences-a-rhythmic-pattern-generator
#1
Horacio G Rotstein, Elisa Schneider, Lidia Szczupak
Motoneurons are not mere output units of neuronal circuits that control motor behavior, but participate in pattern generation. Research on the circuit that controls the crawling motor behavior in leeches indicated that motoneurons participate as modulators of this rhythmic motor pattern. Crawling results from successive bouts of elongation and contraction of the whole leech body. In the isolated segmental ganglia dopamine can induce a rhythmic antiphasic activity of the motoneurons that control contraction (DE-3 motoneurons) and elongation (CV motoneurons)...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28815632/uniform-sized-neurosphere-mediated-motoneuron-differentiation-in-microwell-arrays
#2
Jong Min Lee, Joo Yoon Moon, Mohammed R Shaker, Woong Sun, Bong Geun Chung
We developed the photo-crosslinkable hydrogel microwell arrays for uniform-sized neurosphere-mediated motoneuron differentiation. Neural stem cells (NSCs) were obtained from embryonic cerebral cortex and spinal cord. To generate uniform-sized neurospheres in a homogeneous manner, the dissociated cells were cultured in the hydrogel microwell arrays for 3 days. Uniform-sized neurospheres harvested from microwell arrays were replated into laminin-coated a two-dimensional (2D) substrate. In parallel, uniform-sized neurospheres cultured in microwell arrays were encapsulated by photocrosslinkable gelatin methacrylate (GelMA) hydrogels in a three-dimensional (3D) manner...
August 16, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28814632/intermittent-apnea-elicits-inactivity-induced-phrenic-motor-facilitation-via-a-retinoic-acid-and-protein-synthesis-dependent-pathway
#3
Nathan A Baertsch, Tracy L Baker
Respiratory motoneuron pools must provide rhythmic inspiratory drive that is robust and reliable, yet dynamic enough to respond to respiratory challenges. One form of plasticity that is hypothesized to contribute to motor output stability by sensing and responding to inadequate respiratory neural activity is inactivity-induced phrenic motor facilitation (iPMF), an increase in inspiratory output triggered by a reduction in phrenic synaptic inputs. Evidence suggests that mechanisms giving rise to iPMF differ depending on the pattern of reduced respiratory neural activity (i...
August 16, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28808928/regulation-of-survival-motor-neuron-protein-by-the-nuclear-factor-kappa-b-pathway-in-mouse-spinal-cord-motoneurons
#4
Saravanan Arumugam, Stefka Mincheva-Tasheva, Ambika Periyakaruppiah, Sandra de la Fuente, Rosa M Soler, Ana Garcera
Survival motor neuron (SMN) protein deficiency causes the genetic neuromuscular disorder spinal muscular atrophy (SMA), characterized by spinal cord motoneuron degeneration. Since SMN protein level is critical to disease onset and severity, analysis of the mechanisms involved in SMN stability is one of the central goals of SMA research. Here, we describe the role of several members of the NF-κB pathway in regulating SMN in motoneurons. NF-κB is one of the main regulators of motoneuron survival and pharmacological inhibition of NF-κB pathway activity also induces mouse survival motor neuron (Smn) protein decrease...
August 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28803760/mechanism-of-action-of-botulinum-neurotoxin-unexpected-consequences
#5
REVIEW
Mark Hallett
Botulinum neurotoxin (BoNT) is a widely used therapeutic in part because its mechanism of action is much wider than initially expected. Since BoNT is taken up more avidly in active presynaptic terminals, there is some selectivity for weakening muscles involved in frequent involuntary movements. BoNT blocks gamma motoneurons as well as alpha motoneurons, hence reducing afferent spindle activity which appears to have a favorable effect. Some BoNT is retrogradely transported in the motor axons, leading at least to reduction in recurrent inhibition mediated by the Renshaw cell...
August 10, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28801400/protein-misfolding-amyotrophic-lateral-sclerosis-and-guanabenz-protocol-for-a-phase-ii-rct-with-futility-design-promise-trial
#6
Eleonora Dalla Bella, Irene Tramacere, Giovanni Antonini, Giuseppe Borghero, Margherita Capasso, Claudia Caponnetto, Adriano Chiò, Massimo Corbo, Roberto Eleopra, Massimiliano Filosto, Fabio Giannini, Enrico Granieri, Vincenzo La Bella, Christian Lunetta, Jessica Mandrioli, Letizia Mazzini, Sonia Messina, Maria Rosaria Monsurrò, Gabriele Mora, Nilo Riva, Romana Rizzi, Gabriele Siciliano, Vincenzo Silani, Isabella Simone, Gianni Sorarù, Paolo Volanti, Giuseppe Lauria
INTRODUCTION: Recent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug...
August 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28798955/super-resolution-microscopy-reveals-a-nanoscale-organization-of-acetylcholine-receptors-for-trans-synaptic-alignment-at-neuromuscular-synapses
#7
Amanda L York, James Q Zheng
The neuromuscular junction (NMJ) is a chemical synapse formed between motoneurons and skeletal muscle fibers. The vertebrate NMJ uses acetylcholine (ACh) as the neurotransmitter and features numerous invaginations of the postsynaptic muscle membrane termed junctional folds. ACh receptors (AChRs) are believed to be concentrated on the crest of junctional folds but their spatial organization remains to be fully understood. In this study, we utilized super-resolution microscopy to examine the nanoscale organization of AChRs at NMJ...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28791705/ascending-pathways-that-mediate-cholinergic-modulation-of-lumbar-motor-activity
#8
REVIEW
Lili Anglister, Meir Cherniak, Aharon Lev-Tov
Deciphering neuronal pathways that reactivate spinal central pattern generators (CPGs) and modulate the activity of spinal motoneurons in mammals in the absence of supraspinal control is important for understanding of neural control of movement and for developing novel therapeutic approaches to improve the mobility of spinal cord injury patients. Previously, we showed that the sacral and lumbar cholinergic system could potently modulate the locomotor CPGs in newborn rodents. Here, we review these and our more recent studies of sacral relay neurons with lumbar projections to the locomotor CPGs and to lumbar motoneurons and demonstrate that sacral and lumbar cholinergic components have the capacity to control the frequency of the locomotor CPGs and at the same time the motor output of the activated lumbar motoneurons during motor behavior...
August 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28771790/motoneuron-activity-is-required-for-enhancements-in-functional-recovery-after-peripheral-nerve-injury-in-exercised-female-mice
#9
Poonam B Jaiswal, Jack K Tung, Robert E Gross, Arthur W English
Inhibitory luminopsins (iLMO2) integrate opto- and chemo-genetic approaches and allow for cell-type specific inhibition of neuronal activity. When exposed to a Renilla luciferase substrate, Coelenterazine (CTZ), iLMO2 generates bioluminescence-mediated activation of its amino-terminal halorhodopsin, resulting in neuronal inhibition. Moderate daily exercise in the form of interval treadmill-training (IT) applied following a peripheral nerve injury results in enhanced motor axon regeneration and muscle fiber reinnervation in female mice...
August 3, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28751609/control-of-species-dependent-cortico-motoneuronal-connections-underlying-manual-dexterity
#10
Zirong Gu, John Kalamboglas, Shin Yoshioka, Wenqi Han, Zhuo Li, Yuka Imamura Kawasawa, Sirisha Pochareddy, Zhen Li, Fuchen Liu, Xuming Xu, Sagara Wijeratne, Masaki Ueno, Emily Blatz, Joseph Salomone, Atsushi Kumanogoh, Mladen-Roko Rasin, Brian Gebelein, Matthew T Weirauch, Nenad Sestan, John H Martin, Yutaka Yoshida
Superior manual dexterity in higher primates emerged together with the appearance of cortico-motoneuronal (CM) connections during the evolution of the mammalian corticospinal (CS) system. Previously thought to be specific to higher primates, we identified transient CM connections in early postnatal mice, which are eventually eliminated by Sema6D-PlexA1 signaling. PlexA1 mutant mice maintain CM connections into adulthood and exhibit superior manual dexterity as compared with that of controls. Last, differing PlexA1 expression in layer 5 of the motor cortex, which is strong in wild-type mice but weak in humans, may be explained by FEZF2-mediated cis-regulatory elements that are found only in higher primates...
July 28, 2017: Science
https://www.readbyqxmd.com/read/28751456/intermittent-hypoxia-enhances-functional-connectivity-of-mid-cervical-spinal-interneurons
#11
K A Streeter, M D Sunshine, S Patel, E J Gonzalez-Rothi, P J Reier, D M Baekey, D D Fuller
Brief, intermittent oxygen reductions (acute intermittent hypoxia, AIH) evokes spinal plasticity. Models of AIH-induced neuroplasticity have focused on motoneurons; however, most mid-cervical interneurons (C-INs) also respond to hypoxia. We hypothesized that AIH would alter the functional connectivity between C-INs and induce persistent changes in discharge. Bilateral phrenic nerve activity was recorded in anesthetized and ventilated adult male rats and a multi-electrode array was used to record C4/5 spinal discharge before (baseline, BL), during, and 15 min after 3, 5-min hypoxic episodes (11% O2, H1-H3)...
July 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28747469/alpha-motoneurons-maintain-biophysical-heterogeneity-in-obesity-and-diabetes-in-zucker-rats
#12
Christopher W MacDonell, Jeremy W Chopek, Kalan R Gardiner, Phillip F Gardiner
Small diameter sensory dysfunction resulting from diabetes has received much attention in the literature, while the impact of diabetes on alpha-motoneurons (MN) has not. In addition to this, the chance of developing insulin resistance and diabetes is increased in obesity. No study has examined the impact of obesity or diabetes on the biophysical properties of MN. Lean Zucker rats and Zucker Diabetic Fatty (ZDF) rats were separated into Lean, Obese (ZDF fed standard chow) and Diabetic (ZDF fed high fat diet that led to diabetes) groups...
July 26, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28747093/prochlorperazine-increases-kcc2-function-and-reduces-spasticity-after-spinal-cord-injury
#13
Sylvie Liabeuf, Laetitia Stuhl-Gourmand, Florian Gackière, Renzo Mancuso, Irene Sanchez-Brualla, Philippe Marino, Frédéric Brocard, Laurent Vinay
In mature neurons, low intracellular chloride level required for inhibition is maintained by the potassium-chloride co-transporter KCC2. Impairment of Cl- extrusion following KCC2 dysfunction has been involved in many CNS disorders such as seizures, neuropathic pain or spasticity after a spinal cord injury (SCI). This makes KCC2 an appealing drug target for restoring Cl-homeostasis and inhibition in pathological conditions. In the present study, we screen the Prestwick Chemical Library® and identify conventional antipsychotics phenothiazine derivatives as enhancers of KCC2 activity...
July 26, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28744196/extraocular-motor-system-exhibits-a-higher-expression-of-neurotrophins-when-compared-with-other-brainstem-motor-systems
#14
Rosendo G Hernández, Silvia Silva-Hucha, Sara Morcuende, Rosa R de la Cruz, Angel M Pastor, Beatriz Benítez-Temiño
Extraocular motoneurons resist degeneration in diseases such as amyotrophic lateral sclerosis. The main objective of the present work was to characterize the presence of neurotrophins in extraocular motoneurons and muscles of the adult rat. We also compared these results with those obtained from other cranial motor systems, such as facial and hypoglossal, which indeed suffer neurodegeneration. Immunocytochemical analysis was used to describe the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in oculomotor, trochlear, abducens, facial, and hypoglossal nuclei of adult rats, and Western blots were used to describe the presence of neurotrophins in extraocular, facial (buccinator), and tongue muscles, which are innervated by the above-mentioned motoneurons...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28735746/parallel-inhibitory-and-excitatory-trigemino-facial-feedback-circuitry-for-reflexive-vibrissa-movement
#15
Marie-Andrée Bellavance, Jun Takatoh, Jinghao Lu, Maxime Demers, David Kleinfeld, Fan Wang, Martin Deschênes
Animals employ active touch to optimize the acuity of their tactile sensors. Prior experimental results and models lead to the hypothesis that sensory inputs are used in a recurrent manner to tune the position of the sensors. A combination of electrophysiology, intersectional genetic viral labeling and manipulation, and classical tracing allowed us to identify second-order sensorimotor loops that control vibrissa movements by rodents. Facial motoneurons that drive intrinsic muscles to protract the vibrissae receive a short latency inhibitory input, followed by synaptic excitation, from neurons located in the oralis division of the trigeminal sensory complex...
August 2, 2017: Neuron
https://www.readbyqxmd.com/read/28725191/bilateral-reflex-fluctuations-during-rhythmic-movement-of-remote-limb-pairs
#16
Rinaldo A Mezzarane, Tsuyoshi Nakajima, E Paul Zehr
The modulation of spinal cord excitability during rhythmic limb movement reflects the neuronal coordination underlying actions of the arms and legs. Integration of network activity in the spinal cord can be assessed by reflex variability between the limbs, an approach so far very little studied. The present work addresses this question by eliciting Hoffmann (H-) reflexes in both limbs to assess if common drive onto bilateral pools of motoneurons influence spinal cord excitability simultaneously or with a delay between sides...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28725179/fine-tuning-er-stress-signal-transducers-to-treat-amyotrophic-lateral-sclerosis
#17
Danilo B Medinas, Jose V González, Paulina Falcon, Claudio Hetz
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motoneurons and paralysis. The mechanisms underlying neuronal degeneration in ALS are starting to be elucidated, highlighting disturbances in motoneuron proteostasis. Endoplasmic reticulum (ER) stress has emerged as an early pathogenic event underlying motoneuron vulnerability and denervation in ALS. Maintenance of ER proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28724992/opposite-bidirectional-shifts-in-excitation-and-inhibition-in-specific-types-of-dorsal-horn-interneurons-are-associated-with-spasticity-and-pain-post-sci
#18
Olga Kopach, Volodymyr Medvediev, Volodymyr Krotov, Anya Borisyuk, Vitaliy Tsymbaliuk, Nana Voitenko
Spasticity, a common complication after spinal cord injury (SCI), is frequently accompanied by chronic pain. The physiological origin of this pain (critical to its treatment) remains unknown, although spastic motor dysfunction has been related to the hyperexcitability of motoneurons and to changes in spinal sensory processing. Here we show that the pain mechanism involves changes in sensory circuits of the dorsal horn (DH) where nociceptive inputs integrate for pain processing. Spasticity is associated with the DH hyperexcitability resulting from an increase in excitation and disinhibition occurring in two respective types of sensory interneurons...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715117/differential-activation-of-neuronal-and-glial-stat3-in-the-spinal-cord-of-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#19
Tomohiro Ohgomori, Ryo Yamasaki, Hideyuki Takeuchi, Kenji Kadomatsu, Jun-Ichi Kira, Shozo Jinno
Signal transducer and activator of transcription (STAT) proteins are activated by phosphorylation in the spinal cord of patients suffering from amyotrophic lateral sclerosis (ALS). The major scope of our study is a comprehensive histological characterization of the mechanisms underlying neuronal and glial STAT3 activation in the pathogenesis of ALS using SOD1(G93A) mice. We calculated the fold changes (FCs, ratios vs. appropriate controls) of the numerical densities of the following phosphorylated STAT3-positive (pSTAT3)(+) cells - choline acetyltransferase (ChAT)(+) α-motoneurons, ionized calcium-binding adapter molecule 1 (Iba1)(+) microglia, and S100β(+) astrocytes in SOD1(G93A) mice...
August 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28711602/contribution-of-5-ht2a-receptors-on-diaphragmatic-recovery-after-chronic-cervical-spinal-cord-injury
#20
Kun-Ze Lee, Elisa J Gonzalez-Rothi
Unilateral C2 spinal cord hemisection (C2Hx) interrupts bulbospinal respiratory pathways innervating ipsilateral phrenic motoneurons, resulting in cessation of ipsilateral diaphragm motor output. Plasticity within the spinal neural circuitry controlling the diaphragm can induce partial recovery of phrenic bursting which correlates with the time-dependent return of spinal serotonin (5-HT) immunoreactivity in the vicinity of phrenic motoneurons. The 5-HT2A receptor subtype is present on phrenic motoneurons and its expression is up-regulated after cervical spinal cord injury; however the functional role of these receptors following injury has not been clearly defined...
July 12, 2017: Respiratory Physiology & Neurobiology
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