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

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.

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

10.1101/615906 ◽

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.

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

eLife ◽

10.7554/elife.47837 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 6

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.

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

10.1101/617977 ◽

2019 ◽

Cited By ~ 3

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.

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Pulvino-cortical interaction: an integrative role in the control of attention

10.31234/osf.io/g4fn7 ◽

2019 ◽

Author(s):

Alexia Bourgeois ◽

Carole Guedj ◽

Emmanuel Carrera ◽

Patrik Vuilleumier

Keyword(s):

Executive Control ◽

Sensory Information ◽

Relevant Information ◽

Cortical Circuits ◽

Attention And Executive Control ◽

Neural Communication ◽

Subcortical Regions ◽

Theoretical Proposal ◽

Selection Of

Selective attention is a fundamental cognitive function that guides behavior by selecting and prioritizing salient or relevant sensory information of our environment. Despite early evidence and theoretical proposal pointing to an implication of thalamic control in attention, most studies in the past two decades focused on cortical substrates, largely ignoring the contribution of subcortical regions as well as cortico-subcortical interactions. Here, we suggest a key role of the pulvinar in the selection of salient and relevant information via its involvement in priority maps computation. Prioritization may be achieved through a pulvinar- mediated generation of alpha oscillations, which may then modulate neuronal gain in thalamo-cortical circuits. Such mechanism might orchestrate the synchrony of cortico-cortical interaction, by rendering neural communication more effective, precise and selective. We propose that this theoretical framework will support a timely shift from the prevailing cortico- centric view of cognition to a more integrative perspective of thalamic contributions to attention and executive control processes.

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Cortical and Striatal Electroencephalograms and Apomorphine Effects in the FUS Mouse Model of Amyotrophic Lateral Sclerosis

Journal of Alzheimer s Disease ◽

10.3233/jad-201472 ◽

2021 ◽

pp. 1-15

Author(s):

Vasily Vorobyov ◽

Alexander Deev ◽

Frank Sengpiel ◽

Vladimir Nebogatikov ◽

Aleksey A. Ustyugov

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neurons ◽

Cortical Neurons ◽

Primary Motor Cortex ◽

Beta Activity ◽

Systemic Injection ◽

Eeg Spectra ◽

Electroencephalogram Eeg ◽

Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons resulting in muscle atrophy. In contrast to the lower motor neurons, the role of upper (cortical) neurons in ALS is yet unclear. Maturation of locomotor networks is supported by dopaminergic (DA) projections from substantia nigra to the spinal cord and striatum. Objective: To examine the contribution of DA mediation in the striatum-cortex networks in ALS progression. Methods: We studied electroencephalogram (EEG) from striatal putamen (Pt) and primary motor cortex (M1) in ΔFUS(1–359)-transgenic (Tg) mice, a model of ALS. EEG from M1 and Pt were recorded in freely moving young (2-month-old) and older (5-month-old) Tg and non-transgenic (nTg) mice. EEG spectra were analyzed for 30 min before and for 60 min after systemic injection of a DA mimetic, apomorphine (APO), and saline. Results: In young Tg versus nTg mice, baseline EEG spectra in M1 were comparable, whereas in Pt, beta activity in Tg mice was enhanced. In older Tg versus nTg mice, beta dominated in EEG from both M1 and Pt, whereas theta and delta 2 activities were reduced. In younger Tg versus nTg mice, APO increased theta and decreased beta 2 predominantly in M1. In older mice, APO effects in these frequency bands were inversed and accompanied by enhanced delta 2 and attenuated alpha in Tg versus nTg mice. Conclusion: We suggest that revealed EEG modifications in ΔFUS(1–359)-transgenic mice are associated with early alterations in the striatum-cortex interrelations and DA transmission followed by adaptive intracerebral transformations.

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Anatomy and Neural Pathways Modulating Distinct Locomotor Behaviors in Drosophila Larva

Biology ◽

10.3390/biology10020090 ◽

2021 ◽

Vol 10 (2) ◽

pp. 90

Author(s):

Swetha B. M. Gowda ◽

Safa Salim ◽

Farhan Mohammad

Keyword(s):

Motor Neurons ◽

Model Systems ◽

Neural Pathways ◽

Animal Movements ◽

Drosophila Larvae ◽

The Central Nervous System ◽

Drosophila Larva ◽

Locomotor Behaviors ◽

Basic Level

The control of movements is a fundamental feature shared by all animals. At the most basic level, simple movements are generated by coordinated neural activity and muscle contraction patterns that are controlled by the central nervous system. How behavioral responses to various sensory inputs are processed and integrated by the downstream neural network to produce flexible and adaptive behaviors remains an intense area of investigation in many laboratories. Due to recent advances in experimental techniques, many fundamental neural pathways underlying animal movements have now been elucidated. For example, while the role of motor neurons in locomotion has been studied in great detail, the roles of interneurons in animal movements in both basic and noxious environments have only recently been realized. However, the genetic and transmitter identities of many of these interneurons remains unclear. In this review, we provide an overview of the underlying circuitry and neural pathways required by Drosophila larvae to produce successful movements. By improving our understanding of locomotor circuitry in model systems such as Drosophila, we will have a better understanding of how neural circuits in organisms with different bodies and brains lead to distinct locomotion types at the organism level. The understanding of genetic and physiological components of these movements types also provides directions to understand movements in higher organisms.

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Cardiac regeneration: epicardial mediated repair

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2015.2147 ◽

2015 ◽

Vol 282 (1821) ◽

pp. 20152147 ◽

Cited By ~ 17

Author(s):

Teresa Kennedy-Lydon ◽

Nadia Rosenthal

Keyword(s):

Stem Cells ◽

Endothelial Cells ◽

Cardiac Fibroblasts ◽

Cardiac Regeneration ◽

Repair Process ◽

Regenerative Process ◽

Cardiac Stem Cell ◽

Cardiomyocyte Proliferation ◽

Lower Vertebrates

The hearts of lower vertebrates such as fish and salamanders display scarless regeneration following injury, although this feature is lost in adult mammals. The remarkable capacity of the neonatal mammalian heart to regenerate suggests that the underlying machinery required for the regenerative process is evolutionarily retained. Recent studies highlight the epicardial covering of the heart as an important source of the signalling factors required for the repair process. The developing epicardium is also a major source of cardiac fibroblasts, smooth muscle, endothelial cells and stem cells. Here, we examine animal models that are capable of scarless regeneration, the role of the epicardium as a source of cells, signalling mechanisms implicated in the regenerative process and how these mechanisms influence cardiomyocyte proliferation. We also discuss recent advances in cardiac stem cell research and potential therapeutic targets arising from these studies.

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Current Knowledge of Endolysosomal and Autophagy Defects in Hereditary Spastic Paraplegia

Cells ◽

10.3390/cells10071678 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1678

Author(s):

Liriopé Toupenet Marchesi ◽

Marion Leblanc ◽

Giovanni Stevanin

Keyword(s):

Nervous System ◽

Motor Neurons ◽

Neurological Disorders ◽

Hereditary Spastic Paraplegia ◽

Current Knowledge ◽

Spastic Paraplegia ◽

Functional Convergence ◽

The Common ◽

Hsp Genes

Hereditary spastic paraplegia (HSP) refers to a group of neurological disorders involving the degeneration of motor neurons. Due to their clinical and genetic heterogeneity, finding common effective therapeutics is difficult. Therefore, a better understanding of the common pathological mechanisms is necessary. The role of several HSP genes/proteins is linked to the endolysosomal and autophagic pathways, suggesting a functional convergence. Furthermore, impairment of these pathways is particularly interesting since it has been linked to other neurodegenerative diseases, which would suggest that the nervous system is particularly sensitive to the disruption of the endolysosomal and autophagic systems. In this review, we will summarize the involvement of HSP proteins in the endolysosomal and autophagic pathways in order to clarify their functioning and decipher some of the pathological mechanisms leading to HSP.

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Loss of Calretinin in L5a impairs the formation of the barrel cortex leading to abnormal whisker-mediated behaviors

Molecular Brain ◽

10.1186/s13041-021-00775-w ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Mingzhao Su ◽

Junhua Liu ◽

Baocong Yu ◽

Kaixing Zhou ◽

Congli Sun ◽

...

Keyword(s):

Information Integration ◽

Pyramidal Neurons ◽

Barrel Cortex ◽

Sensory Information ◽

Membrane Excitability ◽

Novelty Preference ◽

Layer 4 ◽

Dendritic Complexity ◽

Cortex System

AbstractThe rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. Layer 5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of layer 5a in the development of the barrel cortex remains unclear. Previously, we found that calretinin is dynamically expressed in layer 5a. In this study, we analyzed calretinin KO mice and found that the dendritic complexity and length of layer 5a pyramidal neurons were significantly decreased after calretinin ablation. The membrane excitability and excitatory synaptic transmission of layer 5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, layer 4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Calretinin KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of layer 5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.

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Linking sensory neurons to visually guided behavior: Relating MST activity to steering in a virtual environment

Visual Neuroscience ◽

10.1017/s0952523813000412 ◽

2013 ◽

Vol 30 (5-6) ◽

pp. 315-330 ◽

Cited By ~ 2

Author(s):

SETH W. EGGER ◽

KENNETH H. BRITTEN

Keyword(s):

Cortical Neurons ◽

Traditional Approach ◽

Sensory System ◽

Sensory Information ◽

Neuronal Population ◽

Difficult Problem ◽

Lower Envelope ◽

Visually Guided ◽

Medial Superior Temporal ◽

Visual Cortical

AbstractMany complex behaviors rely on guidance from sensations. To perform these behaviors, the motor system must decode information relevant to the task from the sensory system. However, identifying the neurons responsible for encoding the appropriate sensory information remains a difficult problem for neurophysiologists. A key step toward identifying candidate systems is finding neurons or groups of neurons capable of representing the stimuli adequately to support behavior. A traditional approach involves quantitatively measuring the performance of single neurons and comparing this to the performance of the animal. One of the strongest pieces of evidence in support of a neuronal population being involved in a behavioral task comes from the signals being sufficient to support behavior. Numerous experiments using perceptual decision tasks show that visual cortical neurons in many areas have this property. However, most visually guided behaviors are not categorical but continuous and dynamic. In this article, we review the concept of sufficiency and the tools used to measure neural and behavioral performance. We show how concepts from information theory can be used to measure the ongoing performance of both neurons and animal behavior. Finally, we apply these tools to dorsal medial superior temporal (MSTd) neurons and demonstrate that these neurons can represent stimuli important to navigation to a distant goal. We find that MSTd neurons represent ongoing steering error in a virtual-reality steering task. Although most individual neurons were insufficient to support the behavior, some very nearly matched the animal’s estimation performance. These results are consistent with many results from perceptual experiments and in line with the predictions of Mountcastle’s “lower envelope principle.”

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