Intersegmental coordination of the central pattern generator via interleaved electrical and chemical synapses in zebrafish spinal cord

A significant component of the repetitive dynamics during locomotion in vertebrates is generated within the spinal cord. The legged locomotion of mammals is most likely controled by a hierarchical, multi-layer spinal network structure, while the axial circuitry generating the undulatory swimming motion of animals like lamprey is thought to have only a single layer in each segment. Recent experiments have suggested a hybrid network structure in zebrafish larvae in which two types of excitatory interneurons (V2a-I and V2a-II) both make first-order connections to the brain and last-order connections to the motor pool. These neurons are connected by electrical and chemical synapses across segments. Through computational modeling and an asymptotic perturbation approach we show that this interleaved interaction between the two neuron populations allows the spinal network to quickly establish the correct activation sequence of the segments when starting from random initial conditions and to reduce the dependence of the intersegmental phase difference (ISPD) of the oscillations on the swimming frequency. The latter reduces the frequency dependence of the waveform of the swimming motion. In the model the reduced frequency dependence is largely due to the different impact of chemical and electrical synapses on the ISPD and to the significant spike-frequency adaptation that has been observed experimentally in V2a-II neurons, but not in V2a-I neurons. Our model makes experimentally testable predictions and points to a benefit of the hybrid structure for undulatory locomotion that may not be relevant for legged locomotion.

Face Mask Detection with Raspberry Pi

In the wake of the COVID-19 epidemic, institutions such as the academy are suffering the most from global closure if the current situation haven’t rectified. COVID-19 also known as Serious Acute Respiratory Syndrome Corona virus-2 is an infectious disease that is transmitted to an infected person who talks, sneezes or coughs through respiratory droplets. This spreads quickly through close contact with anyone with the disease, or by touching objects or the infected area. By wearing a face mask under the jaws covering at crowded places or by frequently hygiene at your palms and by using at the minimum of 70% sanitizers which are based on alcohol is the best method for the against of the COVID-19. In this project we have used it ML, OpenCV and TensorFlow face recognition. This the model can be used for security purposes because of course an app that works well for use. In this way MobilenetV2 using a BN-based layout too lightweight and embedded this model with Raspberry pi to make real-time mask discovery, when, SSD (Single Shot Detector) format is used and the spinal network is light. As technology advances, Deep Learning has demonstrated its effectiveness in recognition and classification through image processing. The study uses in-depth reading techniques to distinguish facial recognition and to determine whether a person is wearing a facemask or not. The collected data contains 25,000 images using 224x224 pixel resolution and obtained 96% accuracy with the performance of a trained model. The system enhances the Raspberry Pi-based real-time recognition made by alarms and takes a facial image when the person found is not wearing a facemask. This study is beneficial in combating the spread of the virus and in avoiding contact with it.

Matrix metalloproteinases, purinergic signaling, and epigenetics, hubs in the spinal neuroglial network following nerve injury.

The neuroglial network characterizes synaptic transmission and accounts for both cellular elements (neurons and glia) and neural extracellular matrix (nECM) roles. Glial cells, neuron, and nECMnetwork is strongly interconnected, in physiological and pathological conditions as shownin several neurodegenerative diseases. Purinergic activation and matrix metalloproteinases (MMPs) remodeling of the spinal cord is pivotal in maladaptive plastic changes following peripheral nerve injury (PNI). To understand how purinergic and MMPs inhibition may modulate and potentially reverse the neuroglial network failure, we used the spared nerve injury (SNI) model of the sciatic nerve. Molecular and morphological analysis of astrocytic and microglial activation, purinergic and neurotrophic receptors, Histone Deacetylase (HDAC)1, HDAC2 were analyzed to define the pathways in response to the purinergic and MMPs inhibition. The data suggest complex protein interconnections, which are not passively influenced by epigenetics but actively contribute to modify the transcriptomics machinery. The present study contributes to unveiling the spinal network consistency and ultimately encourages new paths for targeted treatments in neurological diseases with benefits of neuroprotection, plasticity, and functional recovery.

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

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.

Spinal V1 neurons inhibit motor targets locally and sensory targets distally to coordinate locomotion

Rostro-caudal coordination of spinal motor output is essential for locomotion. Most spinal interneurons project axons longitudinally to govern locomotor output, yet their connectivity along this axis remains unclear. In this study, we use larval zebrafish to map synaptic outputs of a major inhibitory population, V1 (Eng1+) neurons, which are implicated in dual sensory and motor functions. We find that V1 neurons exhibit long axons extending rostrally and exclusively ipsilaterally for an average of 6 spinal segments; however, they do not connect uniformly with their post-synaptic targets along the entire length of their axon. Locally, V1 neurons inhibit motor neurons (both fast and slow) and other premotor targets including V2a, V2b and commissural pre-motor neurons. In contrast, V1 neurons make robust inhibitory contacts throughout the rostral extent of their axonal projections onto a dorsal horn sensory population, the Commissural Primary Ascending neurons (CoPAs). In a computational model of the ipsilateral spinal network, we show that this pattern of short range V1 inhibition to motor and premotor neurons is crucial for coordinated rostro-caudal propagation of the locomotor wave. We conclude that spinal network architecture in the longitudinal axis can vary dramatically, with differentially targeted local and distal connections, yielding important consequences for function.

Rostrocaudal Distribution of the C-Fos-Immunopositive Spinal Network Defined by Muscle Activity during Locomotion

The optimization of multisystem neurorehabilitation protocols including electrical spinal cord stimulation and multi-directional tasks training require understanding of underlying circuits mechanisms and distribution of the neuronal network over the spinal cord. In this study we compared the locomotor activity during forward and backward stepping in eighteen adult decerebrated cats. Interneuronal spinal networks responsible for forward and backward stepping were visualized using the C-Fos technique. A bi-modal rostrocaudal distribution of C-Fos-immunopositive neurons over the lumbosacral spinal cord (peaks in the L4/L5 and L6/S1 segments) was revealed. These patterns were compared with motoneuronal pools using Vanderhorst and Holstege scheme; the location of the first peak was correspondent to the motoneurons of the hip flexors and knee extensors, an inter-peak drop was presumably attributed to the motoneurons controlling the adductor muscles. Both were better expressed in cats stepping forward and in parallel, electromyographic (EMG) activity of the hip flexor and knee extensors was higher, while EMG activity of the adductor was lower, during this locomotor mode. On the basis of the present data, which showed greater activity of the adductor muscles and the attributed interneuronal spinal network during backward stepping and according with data about greater demands on postural control systems during backward locomotion, we suppose that the locomotor networks for movements in opposite directions are at least partially different.

The Translesional Spinal Network and Its Reorganization after Spinal Cord Injury

Evidence from preclinical and clinical research suggest that neuromodulation technologies can facilitate the sublesional spinal networks, isolated from supraspinal commands after spinal cord injury (SCI), by reestablishing the levels of excitability and enabling descending motor signals via residual connections. Herein, we evaluate available evidence that sublesional and supralesional spinal circuits could form a translesional spinal network after SCI. We further discuss evidence of translesional network reorganization after SCI in the presence of sensory inputs during motor training. In this review, we evaluate potential mechanisms that underlie translesional circuitry reorganization during neuromodulation and rehabilitation in order to enable motor functions after SCI. We discuss the potential of neuromodulation technologies to engage various components that comprise the translesional network, their functional recovery after SCI, and the implications of the concept of translesional network in development of future neuromodulation, rehabilitation, and neuroprosthetics technologies.

A dynamic role for dopamine receptors in the control of mammalian spinal networks

Dopamine is well known to regulate movement through the differential control of direct and indirect pathways in the striatum that express D1 and D2 receptors respectively. The spinal cord also expresses all dopamine receptors; however, how the specific receptors regulate spinal network output in mammals is poorly understood. We explore the receptor-specific mechanisms that underlie dopaminergic control of spinal network output of neonatal mice during changes in spinal network excitability. During spontaneous activity, which is a characteristic of developing spinal networks operating in a low excitability state, we found that dopamine is primarily inhibitory. We uncover an excitatory D1-mediated effect of dopamine on motoneurons and network output that also involves co-activation with D2 receptors. Critically, these excitatory actions require higher concentrations of dopamine; however, analysis of dopamine concentrations of neonates indicates that endogenous levels of spinal dopamine are low. Because endogenous levels of spinal dopamine are low, this excitatory dopaminergic pathway is likely physiologically-silent at this stage in development. In contrast, the inhibitory effect of dopamine, at low physiological concentrations is mediated by parallel activation of D2, D3, D4 and α2 receptors which is reproduced when endogenous dopamine levels are increased by blocking dopamine reuptake and metabolism. We provide evidence in support of dedicated spinal network components that are controlled by excitatory D1 and inhibitory D2 receptors that is reminiscent of the classic dopaminergic indirect and direct pathway within the striatum. These results indicate that network state is an important factor that dictates receptor-specific and therefore dose-dependent control of neuromodulators on spinal network output and advances our understanding of how neuromodulators regulate neural networks under dynamically changing excitability.

A dynamic role for dopamine receptors in the control of mammalian spinal networks

Dopamine is well known to regulate movement through the differential control of direct and indirect pathways in the striatum that express D1 and D2 receptors respectively. The spinal cord also expresses all dopamine receptors however; how the specific receptors regulate spinal network output in mammals is poorly understood. We explore the receptor-specific mechanisms that underlie dopaminergic control of spinal network output of neonatal mice during changes in spinal network excitability. During spontaneous activity, which is a characteristic of developing spinal networks operating in a low excitability state, we found that dopamine is primarily inhibitory. We uncover an excitatory D1-mediated effect of dopamine on motoneurons and network output that also involves co-activation with D2 receptors. Critically, these excitatory actions require higher concentrations of dopamine; however, analysis of dopamine concentrations of neonates indicates that endogenous levels of spinal dopamine are low. Because endogenous levels of spinal dopamine are low, this excitatory dopaminergic pathway is likely physiologically-silent at this stage in development. In contrast, the inhibitory effect of dopamine, at low physiological concentrations is mediated by parallel activation of D2, D3, D4 and α2 receptors which is reproduced when endogenous dopamine levels are increased by blocking dopamine reuptake and metabolism. We provide evidence in support of dedicated spinal network components that are controlled by excitatory D1 and inhibitory D2 receptors that is reminiscent of the classic dopaminergic indirect and direct pathway within the striatum. These results indicate that network state is an important factor that dictates receptor-specific and therefore dose-dependent control of neuromodulators on spinal network output and advances our understanding of how neuromodulators regulate neural networks under dynamically changing excitability.Significance statementMonoaminergic neuromodulation of neural networks is dependent not only on target receptors but also on network state. We studied the concentration-dependent control of spinal networks of the neonatal mouse, in vitro, during a low excitability state characterized by spontaneous network activity. Spontaneous activity is an essential element for the development of networks. Under these conditions, we defined converging receptor and cellular mechanisms that contribute to the diverse, concentration-dependent control of spinal motor networks by dopamine, in vitro. These experiments advance understanding of how monoamines modulate neuronal networks under dynamically changing excitability conditions and provide evidence of dedicated D1 and D2 regulated network components in the spinal cord that are consistent with those reported in the striatum.