No description available.

No description available.

Midbrain dopamine (DA) neurons play a key role in a wide range of behaviours, from motor control, motivation, reward and reinforcement learning. Disorders of midbrain dopaminergic signaling is involved in a variety of nervous system disorders including Parkinson’s disease, schizophrenia and drug addiction. Understanding the basis of how dopaminergic neuronal activity in the substantia nigra pars compacta (SNc) governs movements, requires a deep appreciation of how afferent inputs of various neurotransmitter systems create a neuronal circuit that precisely modulates DA neuronal excitability. Two brainstem cholinergic neuclei, the laterodorsal tegmental nucleus (LDT) and the pedunculopontine tegmental nucleus (PPT), have major cholinergic projections to the SNc, despite the fact that the precise mechanisms of cholinergic modulation of DA neuronal activity mediated by nAChRs remain unclear. To dissect out the modulatory roles of the cholinergic system in regulating DAergic neuronal activity in the SNc and locomotion, we employed optogenetics along with electrophysiological and behavioural approaches. My results from whole-cell recordings from lateral and medial SNc DA neurons revealed that lateral DA neurons received predominantly excitatory nAChR mediated cholinergic neurotransmission (monosynaptic nicotinic or disynaptic glutamatergic responses) resulting in greater excitability of DA neurons both at 5 and 15 Hz blue LED light stimulation of cholinergic terminals. However, medial SNc DA neurons received predominantly biphasic current responses that were both inhibitory GABAergic and excitatory nAChR mediated cholinergic neurotransmission. This led to a net inhibition of action potential firing of DA neurons at 5 Hz blue LED light stimulation of cholinergic terminals, while at 15 Hz stimulation there was an initial inhibition followed by a significant increase of the baseline action potential firing frequency. Furthermore, in vivo optogenetic experiments showed that activation of the cholinergic system in the medial SNc resulted in decreased locomotion, while for the lateral SNc led to increased locomotion. Together our findings provide new insights into the role of the cholinergic system in modulating DA neurons in the SNc. The cholinergic inputs to different subregions of the SNc may regulate the excitability of the DA neurons differentially within a tight range from excitation to inhibition which may translate into different kinds of locomotor behaviour. / Graduate

Les circuits neuronaux sous-tendant la locomotion requièrent d'intégrer à la fois des stimuli sensoriels et l'état physiologique. Cependant, la manière dont ces circuits fonctionnent pendant la locomotion active reste peu comprise. La larve de poisson zèbre est un organisme vertébré idéal pour étudier cette question de part son répertoire locomoteur simple et son accessibilité à la manipulation génétique. Dans le Chapitre 1, je décris le logiciel que nous avons développé afin de nous permettre de traquer les comportements et caractériser automatiquement les modules locomoteurs à haut débit. Les interneurones V2a sont des neurones excitateurs de la moelle épinière et du cerveau postérieur caractérisés par l'expression du facteur de transcription chx10. Afin de tester leur implication dans la locomotion, j'ai, dans le Chapitre 2, validé l'utilisation d'une toxine génétiquement encodée dans le but d'inhiber la population chx10 positive in vivo. Par analyse comportementale, enregistrements de locomotion fictive et imagerie calcique, nous avons montré que les V2as sont impliqués différemment dans la locomotion lente et rapide. Les neurones contactant le liquide céphalorachidien (NcLCRs) relaient des informations sensorielles aux circuits moteurs. Par ciblage génétique, imagerie calcique, pharmacologie et électrophysiologie, j'ai, dans le Chapitre 3, investigué le rôle de l'activité spontanée dans les NcLCRs. J'ai montré que l'ouverture de canaux PKD2L1 représentait une source intrinsèque d'activité spontanée dans les NcLCRs. Ces résultats offrent une meilleure compréhension de la manière dont les interactions dynamiques structurent les sorties locomotrices in vivo. / The neural networks that underlie locomotion are complex and require integration of sensory input and physiological state. However, how these networks function during active locomotion to incorporate sensory input from the environment and the internal state of the animal remains poorly understand. The zebrafish larva is an ideal vertebrate to study these questions thanks to its simple locomotor repertoire, transparency, and amenability to genetic manipulation. In Chapter 1, I describe a program to track behavior at high speeds and automatically characterize locomotor patterns in a high-throughput manner. V2a interneurons are excitatory interneurons in the spinal cord and hindbrain identified by the chx10 transcription factor. In Chapter 2, I validated the use of a genetically-encoded botulinum toxin to silence the chx10 population in vivo. Using fictive locomotor recordings and calcium imaging, I demonstrated that silencing V2as leads to decreased activity in primary motor neurons during fast swimming, corresponding to a lower swimming frequency in V2a-silenced larvae. Cerebrospinal fluid-contacting neurons (CSF-cNs) are intraspinal neurons that relay sensory information to motor circuits. CSF-cNs in diverse species express GABA and the transient receptor potential channel PKD2L1. In Chapter 3, I used genetic targeting, calcium imaging, pharmacology, and electrophysiology to investigate the role of spontaneous activity in CSF-cNs. I showed that single channel opening of PKD2L1 represents an intrinsic source of spontaneous activity in CSF-cNs. These tools and results will allow a more complete picture of how dynamic interactions shape locomotor output in vivo.

Title: Fylogenetic aspects of human locomotion Objectives: To find fylogenetic connection between human locomotion and animal locomotion as animal are considered to be our predecessors. Methods: Study and analysis of accessible literary sources. The results gained in the research will be generalized and used to find the fylogenetic connection of human and animal locomotion. Results: Similar locomotive principles happened to be found in connection with first vertebrates, amphibians, birds, mammals and humans. The need for presence of punctum fixum was also found to implement the crossed motion model. There were summarized necessary adaptations to bipedal human locomotion. Key words: punctum fixum, kvadrupedal crossed model, human locomotion, motion, development

Our goal is to introduce a novel method for representing, generalising, and comparing gaits; particularly, walking gait. Human walking gaits are a result of complex, interdependent factors that include variations resulting from embodiments, environment and tasks, making techniques that use average template frameworks suboptimal for systematic analysis or corrective interventions. The proposed work aims to devise methodologies for being able to represent gaits and gait transitions such that optimal policies that eliminate the inter-personal variations from tasks and embodiment may be recovered. Our approach is built upon (i) work in the domain of null-space policy recovery and (ii) previous work in generalisation for point-to-point movements. The problem is formalised using a walking phase model, and the null-space learning method is used to generalise a consistent policy from multiple observations with rich variations. Once recovered, the underlying policies (mapped to different gait phases) can serve as reference guideline to quantify and identify pathological gaits while being robust against interpersonal and task variations. To validate our methods, we have demonstrated robustness of our method with simulated sagittal 2-link gait data with multiple ground truth constraints and policies. Pathological gait identification was then tested on real-world human gait data with induced gait abnormality, with the proposed method showing significant robustness to variations in speed and embodiment compared to template based methods. Future work will extend this to kinetic features and higher degree-of-freedom.

No description available.

Certaines observations suggèrent que les afférences méchano-sensorielles peuvent moduler l’activité des générateurs centraux du rythme locomoteur (ou Central Pattern Generators, CPGs). Cependant, il est impossible d’explorer les circuits neuronaux sous-jacents chez l’animal en mouvement à l’aide d’enregistrements électrophysiologiques lors d’expériences de locomotion dite « fictive ». Dans cette étude, nous avons enregistré de façon sélective et non-invasive les neurones moteurs et sensoriels dans la moelle épinière pendant la locomotion active en ciblant génétiquement le senseur bioluminescent GFP-Aequorin chez la larve de poisson zèbre. En utilisant l’imagerie calcique à l’échelle des neurones individuels, nous confirmons que les signaux de bioluminescence reflètent bien le recrutement différentiel des groupes de motoneurones spinaux durant la locomotion active. La diminution importante de ces signaux chez des animaux paralysés ou des mutants immobiles démontre que le retour méchano-sensoriel augmente le recrutement des motoneurones spinaux pendant la locomotion active. En accord avec cette observation, nous montrons que les neurones méchano-sensoriels spinaux sont en effet recrutés chez les animaux en mouvement, et que leur inhibition affecte les réflexes d’échappement chez des larves nageant librement. L’ensemble de ces résultats met en lumière la contribution du retour méchano-sensoriel sur la production locomotrice et les différences qui en résultent entre les locomotions active et fictive. / There is converging evidence that mechanosensory feedback modulates the activity of spinal central pattern generators underlying vertebrate locomotion. However, probing the underlying circuits in behaving animals is not possible in “fictive” locomotion electrophysiological recordings. Here, we achieve selective and non-invasive monitoring of spinal motor and sensory neurons during active locomotion by genetically targeting the bioluminescent sensor GFP-Aequorin in larval zebrafish. Using GCaMP imaging of individual neurons, we confirm that bioluminescence signals reflect the differential recruitment of motor pools during motion. Their significant reduction in paralyzed animals and immotile mutants demonstrates that mechanosensory feedback enhances the recruitment of spinal motor neurons during active locomotion. Accordingly, we show that spinal mechanosensory neurons are recruited in moving animals and that their silencing impairs escapes in freely behaving larvae. Altogether, these results shed light on the contribution of mechanosensory feedback to motor output and the resulting differences between active and fictive locomotion.

The combination or integration of locomotion modes, is analyzed through the design, development, and verification of a miniature integrated jumping and gliding robot, the MultiMo-Bat, which is inspired by the locomotion strategies of vampire bats, locusts, and pelicans. This robot has a mass of between 100 and 162 grams and exhibits high jumping and gliding performance, reaching heights of over 4.5 meters, to overcome obstacles in the environment. Integration results in a smaller, lighter robot with high cooperation between the modes. This thesis presents a previously unstudied robot design concept and highlights the understudied evolutionary concept within organism mobility of integration of locomotion modes. High performance locomotion modes also require high energy density actuators. To this end, a design methodology is developed for tailoring magnetic springs to the characteristics of shape memory alloy-actuated mechanisms, which allow the MultiMo-Bat to reach jumping heights of 3.5 m with active wing deployment and full controller. Through a combinations of permanent magnets, a magnetic spring can be customized to desired characteristics; theoretically any welldefined function of force vs. displacement can be created. The methodology is not limited to SMA but can be adapted to any smart actuator, joint, or situation which requires a fixed complex force-displacement relationship with extension other interactions and magnetic field design. Robotic locomotion is also much more idealized than that of their biological counter parts. This thesis serves to highlight just how non-ideal, yet robust, biological locomotion can inspire concepts for enhancing the robustness of robot locomotion. We studied the desert locust (Schistocerca gregaria), which is adapted for jumping at the extreme limits of its surface friction, as evident by its morphological adaptations for not only jumping, but slipping. Analysis of both foot morphology and jumping behavior are used to understand how the feet interact with different surfaces, including hydrophobic glass, hydrophilic glass, wood, sandstone, and mesh. The results demonstrate a complex interplay of embodied mechanical intelligence, allowing the foot to interact and adapt passively to different surfaces without burdening the organism with additional tasks. The key morphological and dynamical features are extracted to create a concept for developing multi-Surface Locust Inspired Passively-adaptable (SLIP) feet. A simple interpretation of the concepts are then used to construct a SLIP foot for the MultiMo-Bat. These feet allow the MultiMo-Bat to reach jumping heights of well over 4 m, greater than any other electrically powered robot, and this is achieved on a 45 degree angled surface while slipping. The SLIP foot concept can be directly applied to a wide range of robot size scales, thus enhancing their dynamic terrestrial locomotion on variable surfaces.

In the amphibious fish Polypterus senegalus, focussing on lateral line, vision and electrosensation, we investigated sensory abilities, their interactions, and changes in their effects on locomotor behaviour between aquatic and terrestrial environments. First, we blocked lateral line, vision, or both, and examined effects on locomotion in both environments. Both senses affected both types of locomotion. When fish could see but not feel, variation in several kinematic variables increased, suggesting that sensory integration may affect locomotor control. Next, we assessed response to optokinetic stimuli of varying size and speed. Temporal and spatial visual acuity were both low, as expected in a nocturnal ambush predator. Visual ability in air was much reduced. Finally, we attempted to record electrogenesis in Polypterus, but did not observe the electric discharges reported in a previous study. Future studies might examine changes in sensory function, interaction and importance in behaviour in Polypterus raised in a terrestrial environment.