scholarly journals Spinal V2b neurons reveal a role for ipsilateral inhibition in speed control

2019 ◽  
Author(s):  
Rebecca A. Callahan ◽  
Richard Roberts ◽  
Mohini Sengupta ◽  
Yukiko Kimura ◽  
Shin-ichi Higashijima ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Speed Control ◽  
Morphological Properties ◽  
Larval Zebrafish ◽  
Motor Circuits ◽  
Transgenic Lines ◽  
Left And Right ◽  
Specific Influence

AbstractThe spinal cord contains a diverse array of interneurons that govern motor output. Traditionally, models of spinal circuits have emphasized the role of inhibition in enforcing reciprocal alternation between left and right sides or flexors and extensors. However, recent work has shown that inhibition also increases coincident with excitation during contraction. Here, using larval zebrafish, we investigate the V2b (Gata3+) class of neurons, which contribute to flexor-extensor alternation but are otherwise poorly understood. Using newly generated transgenic lines we define two stable subclasses with distinct neurotransmitter and morphological properties. These two V2b subclasses make direct synapses onto motor neurons with differential targeting to slower and faster circuits. In vivo, optogenetic suppression of V2b activity leads to increases in locomotor speed. We conclude that V2b neurons exert speed-specific influence over axial motor circuits throughout the rostrocaudal axis. Together, these results indicate a new role for ipsilateral inhibition in speed control.

scholarly journals Spinal V2b neurons reveal a role for ipsilateral inhibition in speed control

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Rebecca A Callahan ◽  
Richard Roberts ◽  
Mohini Sengupta ◽  
Yukiko Kimura ◽  
Shin-ichi Higashijima ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Neurons ◽  
Speed Control ◽  
Morphological Properties ◽  
Larval Zebrafish ◽  
Motor Circuits ◽  
Transgenic Lines ◽  
Left And Right

The spinal cord contains a diverse array of interneurons that govern motor output. Traditionally, models of spinal circuits have emphasized the role of inhibition in enforcing reciprocal alternation between left and right sides or flexors and extensors. However, recent work has shown that inhibition also increases coincident with excitation during contraction. Here, using larval zebrafish, we investigate the V2b (Gata3+) class of neurons, which contribute to flexor-extensor alternation but are otherwise poorly understood. Using newly generated transgenic lines we define two stable subclasses with distinct neurotransmitter and morphological properties. These V2b subclasses synapse directly onto motor neurons with differential targeting to speed-specific circuits. In vivo, optogenetic manipulation of V2b activity modulates locomotor frequency: suppressing V2b neurons elicits faster locomotion, whereas activating V2b neurons slows locomotion. We conclude that V2b neurons serve as a brake on axial motor circuits. Together, these results indicate a role for ipsilateral inhibition in speed control.

scholarly journals Genetic Renal Diseases: The Emerging Role of Zebrafish Models

Cells ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 130 ◽  
Author(s):  
Mohamed Elmonem ◽  
Sante Berlingerio ◽  
Lambertus van den Heuvel ◽  
Peter de Witte ◽  
Martin Lowe ◽  
...  
Keyword(s):  
Genetic Diseases ◽  
Cost Effective ◽  
Therapeutic Interventions ◽  
Renal Diseases ◽  
Larval Zebrafish ◽  
Zebrafish Pronephros ◽  
Evaluation Techniques ◽  
Renal Phenotype

The structural and functional similarity of the larval zebrafish pronephros to the human nephron, together with the recent development of easier and more precise techniques to manipulate the zebrafish genome have motivated many researchers to model human renal diseases in the zebrafish. Over the last few years, great advances have been made, not only in the modeling techniques of genetic diseases in the zebrafish, but also in how to validate and exploit these models, crossing the bridge towards more informative explanations of disease pathophysiology and better designed therapeutic interventions in a cost-effective in vivo system. Here, we review the significant progress in these areas giving special attention to the renal phenotype evaluation techniques. We further discuss the future applications of such models, particularly their role in revealing new genetic diseases of the kidney and their potential use in personalized medicine.

scholarly journals Expression of bovine superoxide dismutase in Drosophila melanogaster augments resistance of oxidative stress.

1991 ◽  
Vol 11 (2) ◽  
pp. 632-640 ◽  
Author(s):  
I Reveillaud ◽  
A Niedzwiecki ◽  
K G Bensch ◽  
J E Fleming
Keyword(s):  
Drosophila Melanogaster ◽  
Gene Promoter ◽  
Adult Mortality ◽  
P Elements ◽  
Transgenic Lines ◽  
A Minor ◽  
Radical Damage ◽  
Positive Effect

Superoxide dismutases (SOD) play a major role in the intracellular defense against oxygen radical damage to aerobic cells. In eucaryotes, the cytoplasmic form of the enzyme is a 32-kDa dimer containing two copper and two zinc atoms (CuZn SOD) that catalyzes the dismutation of the superoxide anion (O2-) to H2O2 and O2. Superoxide-mediated damage has been implicated in a number of biological processes, including aging and cancer; however, it is not certain whether endogenously elevated levels of SOD will reduce the pathological events resulting from such damage. To understand the in vivo relationship between an efficient dismutation of O2- and oxidative injury to biological structures, we generated transgenic strains of Drosophila melanogaster overproducing CuZn SOD. This was achieved by microinjecting Drosophila embryos with P-elements containing bovine CuZn SOD cDNA under the control of the Drosophila actin 5c gene promoter. Adult flies of the resulting transformed lines which expressed both mammalian and Drosophila CuZn SOD were then used as a novel model for evaluating the role of oxygen radicals in aging. Our data show that expression of enzymatically active bovine SOD in Drosophila flies confers resistance to paraquat, an O2(-)-generating compound. This is consistent with data on adult mortality, because there was a slight but significant increase in the mean lifespan of several of the transgenic lines. The highest level of expression of the active enzyme in adults was 1.60 times the normal value. Higher levels may have led to the formation of toxic levels of H2O2 during development, since flies that died during the process of eclosion showed an unusual accumulation of lipofuscin (age pigment) in some of their cells. In conclusion, our data show that free-radical detoxification has a minor by positive effect on mean longevity for several strains.

scholarly journals Dpysl2 (CRMP2) is required for the migration of facial branchiomotor neurons in the developing zebrafish embryo

2020 ◽  
Vol 64 (10-11-12) ◽  
pp. 479-484
Author(s):  
Carolina Fiallos-Oliveros ◽  
Toshio Ohshima
Keyword(s):  
Motor Neurons ◽  
System Development ◽  
Nervous System Development ◽  
Knock Out ◽  
Facial Branchiomotor Neurons ◽  
Morpholino Oligonucleotides ◽  
Mutant Phenotypes ◽  
Antisense Morpholino Oligonucleotides

Dihydropyrimidinase-like family proteins (Dpysls) are relevant in several processes during nervous system development; among others, they are involved in axonal growth and cell migration. Dpysl2 (CRMP2) is the most studied member of this family; however, its role in vivo is still being investigated. Our previous studies in zebrafish showed the requirement of Dpysl2 for the proper positioning of caudal primary motor neurons and Rohon-Beard neurons in the spinal cord.In the present study, we show that Dpysl2 is necessary for the proper migration of facial branchiomotor neurons during early development in zebrafish. We generated a dpysl2 knock-out (KO) zebrafish mutant line and used different types of antisense morpholino oligonucleotides (AMO) to analyze the role of Dpysl2 in this process. Both dpysl2 KO mutants and morphants exhibited abnormalities in the migration of these neurons from rhombomers (r) 4 and 5 to 6 and 7. The facial branchiomotor neurons that were expected to be at r6 were still located at r4 and r5 hours after the migration process should have been completed. In addition, mutant phenotypes were rescued by injecting dpysl2 mRNA into the KO embryos. These results indicate that Dpysl2 is involved in the proper migration of facial branchiomotor neurons in developing zebrafish embryos.

scholarly journals Haploinsufficiency of the TDP43 ubiquitin E3 ligase RNF220 leads to ALS-like motor neuron defects in the mouse

2021 ◽  
Author(s):  
Pengcheng Ma ◽  
Yuwei Li ◽  
Huishan Wang ◽  
Bingyu Mao
Keyword(s):  
Motor Neurons ◽  
Regulatory Protein ◽  
E3 Ligase ◽  
Subcellular Location ◽  
Spinal Motor Neurons ◽  
Ubiquitin E3 Ligase ◽  
Lateral Sclerosis

Abstract TDP43 pathology is seen in a large majority of amyotrophic lateral sclerosis (ALS) cases, suggesting a central pathogenic role of this regulatory protein. Clarifying the molecular mechanism controlling TDP43 stability and subcellular location might provide important insights into ALS therapy. The ubiquitin E3 ligase RNF220 is involved in different neural developmental processes through various molecular targets in the mouse. Here, we report that the RNF220+/- mice showed progressively decreasing mobility to different extents, some of which developed typical ALS pathological characteristics in spinal motor neurons, including TDP43 cytoplasmic accumulation, atrocytosis, muscle denervation, and atrophy. Mechanistically, RNF220 interacts with TDP43 in vitro and in vivo and promotes its polyubiquitination and proteasomal degradation. In conclusion, we propose that RNF220 might be a modifier of TDP43 function in vivo and contribute to TDP43 pathology in neurodegenerative disease like ALS.

scholarly journals Little Helpers or Mean Rogue—Role of Microglia in Animal Models of Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 22 (3) ◽  
pp. 993
Author(s):  
Hilal Cihankaya ◽  
Carsten Theiss ◽  
Veronika Matschke
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Disease Onset ◽  
Cellular Level ◽  
Chromosome 9 ◽  
Common Denominator ◽  
Vacuolar Protein ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, causing degeneration of both upper and lower motor neurons in the central nervous system (CNS). ALS patients suffer from hyperreflexia, spasticity, paralysis and muscle atrophy and typically die due to respiratory failure 1–5 years after disease onset. In addition to the degeneration of motor neurons on the cellular level, ALS has been associated with neuroinflammation, such as microgliosis. Microglial activation in ALS can either be protective or degenerative to the neurons. Among others, mutations in superoxide dismutase 1 (SOD1), chromosome 9 open reading frame 72 (C9Orf72), transactive response DNA binding protein (TDP) 43 and vacuolar protein sorting-associated protein 54 (VPS54) genes have been associated with ALS. Here, we describe the dual role and functionality of microglia in four different in vivo ALS models and search for the lowest common denominator with respect to the role of microglia in the highly heterogeneous disease of ALS.

scholarly journals The role of intraspinal sensory neurons in the control of quadrupedal locomotion

2021 ◽  
Author(s):  
Katrin Gerstmann ◽  
Nina Jurcic ◽  
Severine Kunz ◽  
Nicolas Wanaverbecq ◽  
Niccolo Zampieri
Keyword(s):  
Motor Neurons ◽  
Sensory System ◽  
Sensory Information ◽  
Mouse Genetics ◽  
Quadrupedal Locomotion ◽  
Foot Placement ◽  
Terrestrial Locomotion ◽  
Motor Circuits ◽  
Lower Vertebrates

From swimming to walking and flying, animals have evolved specific locomotor strategies to thrive in different habitats. All types of locomotion depend on integration of motor commands and sensory information to generate precise movements. Cerebrospinal fluid-contacting neurons (CSF-cN) constitute a vertebrate sensory system that monitors CSF composition and flow. In fish, CSF-cN modulate swimming activity in response to changes in pH and bending of the spinal cord, yet their role in higher vertebrates remains unknown. We used mouse genetics to study their function in quadrupedal locomotion and found that CSF-cN are directly integrated into spinal motor circuits by forming connections with motor neurons and premotor interneurons. Elimination of CSF-cN selectively perturbs the accuracy of foot placement required for skilled movements at the balance beam and horizontal ladder. These results identify an important role for mouse CSF-cN in adaptive motor control and indicate that this sensory system evolved a novel function from lower vertebrates to accommodate the biomechanical requirements of terrestrial locomotion.

Expression of bovine superoxide dismutase in Drosophila melanogaster augments resistance of oxidative stress

1991 ◽  
Vol 11 (2) ◽  
pp. 632-640 ◽  
Author(s):  
I Reveillaud ◽  
A Niedzwiecki ◽  
K G Bensch ◽  
J E Fleming
Keyword(s):  
Drosophila Melanogaster ◽  
Gene Promoter ◽  
Adult Mortality ◽  
P Elements ◽  
Transgenic Lines ◽  
A Minor ◽  
Radical Damage ◽  
Positive Effect

Superoxide dismutases (SOD) play a major role in the intracellular defense against oxygen radical damage to aerobic cells. In eucaryotes, the cytoplasmic form of the enzyme is a 32-kDa dimer containing two copper and two zinc atoms (CuZn SOD) that catalyzes the dismutation of the superoxide anion (O2-) to H2O2 and O2. Superoxide-mediated damage has been implicated in a number of biological processes, including aging and cancer; however, it is not certain whether endogenously elevated levels of SOD will reduce the pathological events resulting from such damage. To understand the in vivo relationship between an efficient dismutation of O2- and oxidative injury to biological structures, we generated transgenic strains of Drosophila melanogaster overproducing CuZn SOD. This was achieved by microinjecting Drosophila embryos with P-elements containing bovine CuZn SOD cDNA under the control of the Drosophila actin 5c gene promoter. Adult flies of the resulting transformed lines which expressed both mammalian and Drosophila CuZn SOD were then used as a novel model for evaluating the role of oxygen radicals in aging. Our data show that expression of enzymatically active bovine SOD in Drosophila flies confers resistance to paraquat, an O2(-)-generating compound. This is consistent with data on adult mortality, because there was a slight but significant increase in the mean lifespan of several of the transgenic lines. The highest level of expression of the active enzyme in adults was 1.60 times the normal value. Higher levels may have led to the formation of toxic levels of H2O2 during development, since flies that died during the process of eclosion showed an unusual accumulation of lipofuscin (age pigment) in some of their cells. In conclusion, our data show that free-radical detoxification has a minor by positive effect on mean longevity for several strains.

scholarly journals ADrosophilalarval premotor/motor neuron connectome generating two behaviors via distinct spatio-temporal muscle activity

2019 ◽  
Author(s):  
Aref Arzan Zarin ◽  
Brandon Mark ◽  
Albert Cardona ◽  
Ashok Litwin-Kumar ◽  
Chris Q. Doe
Keyword(s):  
Motor Neurons ◽  
Muscle Activity ◽  
Recurrent Network ◽  
The Body ◽  
Temporal Muscle ◽  
Motor Circuits ◽  
Premotor Neurons ◽  
Spatio Temporal ◽  
Locomotor Behaviors

AbstractAnimals generate diverse motor behaviors, yet how the same motor neurons generate distinct behaviors remains an open question.Drosophilalarvae have multiple behaviors – e.g. forward crawling, backward crawling, self-righting and escape – and all of the body wall motor neurons (MNs) driving these behaviors have been identified. Despite impressive progress in mapping larval motor circuits, the role of most motor neurons in locomotion remains untested, the majority of premotor neurons (PMNs) remain to be identified, and a full understanding of proprioceptor-PMN-MN connectivity is missing. Here we report a comprehensive larval proprioceptor-PMN-MN connectome; describe individual muscle/MN phase activity during both forward and backward locomotor behaviors; identify PMN-MN connectivity motifs that could generate muscle activity phase relationships, plus selected experimental validation; identify proprioceptor-PMN connectivity that provides an anatomical explanation for the role of proprioception in promoting locomotor velocity; and identify a new candidate escape motor circuit. Finally, we generate a recurrent network model that produces the observed sequence of motor activity, showing that the identified pool of premotor neurons is sufficient to generate two distinct larval behaviors. We conclude that different locomotor behaviors can be generated by a specific group of premotor neurons generating behavior-specific motor rhythms.

scholarly journals V3 Interneurons Regulate Locomotor Vigor by Recruitment of Spinal Motor Neurons During Fictive Swimming in Larval Zebrafish

2021 ◽  
Author(s):  
Timothy D. Wiggin ◽  
Jacob E. Montgomery ◽  
Amanda J. Brunick ◽  
Jack H. Peck ◽  
Mark A. Masino
Keyword(s):  
Motor Control ◽  
Motor Neurons ◽  
Neuronal Population ◽  
Fine Motor ◽  
Spinal Interneurons ◽  
Spinal Motor Neurons ◽  
Larval Zebrafish ◽  
Spinal Motor ◽  
Spinal Network

ABSTRACTSurvival for vertebrate animals is dependent on the ability to successfully find food, locate a mate, and avoid predation. Each of these behaviors requires fine motor control, which is set by a combination of kinematic properties. For example, the frequency and amplitude (vigor; strength) of motor output combine to determine features of locomotion such as distance traveled and speed. Although there is a good understanding of how different populations of excitatory spinal interneurons establish locomotor frequency, there is not a mechanistic understanding for how locomotor vigor is established. Recent evidence indicates that locomotor vigor is regulated in part by subsets of identified excitatory spinal interneurons (INs), such as the V2a neuronal population in adult zebrafish. Here we provide evidence that the majority of V3 interneurons (V3-INs), which are a developmentally and genetically defined population of ventromedial glutamatergic spinal neurons, are active during fictive swimming. Further, that targeted ablation of V3-INs reduces the proportion of active MNs during fictive swimming, but ablation does not affect the locomotor frequencies produced. These data are consistent with a role of V3-INs in providing excitatory drive to spinal motor neurons during swimming in larval zebrafish, which suggests that locomotor vigor (but not locomotor frequency) may be regulated, in part, by V3-INs.SIGNIFICANCE STATEMENTCurrently, there is a fundamental lack of knowledge about the cellular and spinal network properties that produce locomotor vigor in vertebrates. Here we show, directly for the first time, that V3 interneurons in zebrafish larvae are active duringin vivofictive locomotion, and that targeted ablation of the spinal V3 interneuron population reduces the probability of motoneuron firing during fictive swimming. In contrast to V2a interneurons, ablation of V3 interneurons does not affect locomotor frequency, the fictive neural correlate of speed, which clarifies their role in motor control rather than rhythm generation. Thus, we propose that the V3 interneuron subpopulation is a source of excitation in the vertebrate locomotor neural circuitry that regulates locomotor vigor independently of speed.

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