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Nerve cells are organized into complex networks that comprise the building blocks of our nervous system. Neurons communicate by transmitting messenger molecules released from synaptic vesicles. Alterations in neuronal circuitry and synaptic signaling contribute to a wide range of neurological conditions, often with consequences for movement. Intrinsic neuronal networks in the spinal cord serve to coordinate vital rhythmic motor functions. In spite of extensive efforts to address the organization of these neural circuits, much remains to be revealed regarding the identity and function of specific interneuron cell types and how neuromodulation tune network activity. In this thesis, two novel genes initially identified as markers for spinal neuronal populations were investigated: Slc10a4 and Dmrt3. The orphan transporter SLC10A4 was found to be expressed on synaptic vesicles of the cholinergic system, including motor neurons, as well as in the monoaminergic system, including dopaminergic, serotonergic and noradrenergic nuclei. Thus, it constitutes a novel molecular denominator shared by these classic neuromodulatory systems. SLC10A4 was found to influence vesicular transport of dopamine and affect neuronal release and reuptake efficiency in the striatum. Mice lacking Slc10a4 displayed impaired monoamine homeostasis and were hypersensitive to the drugs amphetamine and tranylcypromine. These findings demonstrate that SLC10A4 is capable of modulating the modulatory systems of the brain with potential clinical relevance for neurological and mental disorders. The transcription factor encoded by Dmrt3 was found to be expressed in a population of inhibitory commissural interneurons originating from the dorsal interneuron 6 (dI6) domain in the spinal cord. In parallel, a genome-wide association study revealed that a non-sense mutation in horse DMRT3 is permissive for the ability to perform pace among other alternate gaits. Further analysis of Dmrt3 null mutant mice showed that Dmrt3 has a central role for spinal neuronal network development with consequences for locomotor behavior. The dI6 class has been suggested to take part in motor circuits but remains one of the least studied classes due to lack of molecular markers. To further investigate the Dmrt3-derived neurons, and the dI6 population in general, a Dmrt3Cre mouse line was generated which allowed for characterization on the molecular, cellular and  behavioral level. It was found that Dmrt3 neurons synapse onto motor neurons, receive extensive synaptic inputs from various neuronal sources and are rhythmically active during fictive locomotion. Furthermore, silencing of Dmrt3 neurons in Dmrt3Cre;Viaatlx/lx mice led to impaired motor coordination and alterations in gait, together demonstrating the importance of this neuronal population in the control of movement.

Evidence suggests that a flexible, task-dependent neuronal coupling of the upper and lower limbs exists, and this allows for coordinated rhythmic movement (e.g., locomotion). To further understand this coupling, muscle activity and reflex patterns can be examined by stimulating peripheral nerves during various tasks. In particular, cutaneous reflexes demonstrate task- and phase-dependent modulation, making them highly sensitive probes into neural activity during rhythmic movement. The purpose of this research was to use reflex modulation to probe the neuronal coupling between the arms and legs. This was done using a cycling paradigm that allowed for the separation of arm and leg movement, which is difficult to do in most forms of locomotion (i.e., walking). Participants (N=14) performed three cycling tasks: 1)arm cycling with stationary legs (ARM); 2)leg cycling with stationary arms (LEG); and 3)combined arm and leg cycling (ARM&LEG). The relative contributions from the arms and legs to reflex modulation in the legs were then determined throughout the movement cycle. It was hypothesized that the individual contributions from arm and leg movement to reflex amplitudes in the legs would summate during the combined arm and leg task. This hypothesis was tested explicitly by comparing the reflex amplitudes expressed during the combined arm and leg task to the algebraic summation of the reflex amplitudes expressed during the arm cycling and leg cycling tasks alone. Static trials were also collected at 4 positions within each task. Tasks were performed under two different cycling conditions: 1) Focused tibialis anterior (TA) contraction (FCC) (N=14); and 2) normal cycling (NC) (n=8). During all trials, stimulation was delivered pseudorandomly throughout the movement cycle to the superficial peroneal nerve at the ankle. EMG was recorded bilaterally from muscles in the arms and legs, and kinematic data were obtained from the elbow and knee joints. Results focused on the middle latency reflex amplitudes in TA (ipsilateral to the site of stimulation) during the FCC condition because the focused contraction did not significantly alter EMG or reflex activity in the other leg muscles studied. This also allowed for comparisons among tasks at comparable EMG levels. The main finding from this study was that reflex amplitudes expressed during the ARM&LEG task agreed with the predicted algebraic summation of reflex amplitudes expressed during the ARM and LEG tasks separately. Examination of the relative contributions from the arms and legs to the reflexes expressed during the combined task revealed that across all movement phases the legs accounted for 33% (p < .05) of the variance observed during the ARM&LEG task, while the arms accounted for an additional 5% (p < .05). The relative contributions from the arms and legs were also found to be phase dependent. That is, the relative contribution from the arms was dominant during the power phase of leg cycling while the leg contribution was dominant during the recovery phase. More specifically, the greatest contribution from the arms accounted for 57% of the variance in the ARM&LEG task when the leg was at 11 o'clock (p < .05) and the greatest contribution from the legs was 71% of the variance accounted for when the legs were at 9 o'clock (p < .05). Additionally, characteristic patterns of reflex amplitude modulation (i.e., phase- and task-dependent modulation) were observed during most of the cycling tasks. In conclusion, these findings suggest evidence for a neuronal coupling between the rhythm generators responsible for arm and leg movement which is functionally gated throughout the movement cycle of a combined arm and leg task.

Rhythmic locomotor activity involving the arms or the legs results in task and phase specific Hoffmann (H)-reflex modulation between the two arms or between the two legs. As well, specific ipsilateral and contralateral movement effects are observed. Recently it has been found that there is also interlimb (between arms and legs) task modulation of the H-reflex, using a rhythmic arm cycling paradigm. That is, the stationary Soleus H-reflex amplitude during arm cycling was attenuated when compared to a static condition (Frigon et al. 2004). The specific parameters of the arm cycling movement which may contribute to this attenuation however are unknown. The purpose of this research was to examine whether the interlimb Soleus H-reflex suppression is specific to: the phase of the arm movement; the movement of both arms; arm excursion; and, rate of arm cycling. Participants sat in a custom designed chair to prevent leg and trunk movement and performed bilateral arm cycling at frequencies of 1 and 2 Hz and with short and long crank lengths (to alter arm range of motion; ROM). As well. ipsilateral (relative to leg stimulated) and contralateral single arm cycling were performed at 1Hz with a long crank length. The Tibial nerve at the popliteal fossa was stimulated psuedorandomly at four phases of the arm cycle and changes in the Soleus H-reflex were recorded while maintaining a small, but stable motor (M)-wave for all trials. EMG was recorded from the Soleus, Tibialis Anterior. Vastus Lateralis and the Anterior Deltoid muscles. Peak to peak amplitudes of the H-reflex from each participant were determined off line and normalized to the M-max determined from individual M-H recruitment curves. Results indicate comparable suppressive effects in all phases of the arm movement, and with bilateral or unilateral cycling. The large ROM and the 2 Hz frequency of movement resulted in a stronger inhibition than with the small ROM and the 1 Hz arm cycling. This suggests that neural processes associated with generating both the rhythmic arm cycling pattern and the peripheral feedback from the arms, have an effect on the H-reflex modulation in the legs. We conclude that a general, rather than a specific, signal related to rhythmic arm muscle activity mediates the suppression of Soleus H-reflex during arm cycling.

In common with animal species, evidence in humans suggests that similar neural mechanisms (e.g. locomotor central pattern generator (CPG)) regulate rhythmic movements in both arm and leg and that interlimb neural connections coordinate movement between upper and lower limbs ; however, by comparison the evidence in humans is limited. This thesis focused upon exploring the neural control of rhythmic arm cycling and the influence of the neural control of arm cycling on the neural circuits controlling the legs. Specifically, the effect of five different arm cycling paradigms on EMG and reflex responses in arm and leg muscles were explored. First, the pattern of muscle activity and cutaneous reflex modulation evoked with electrical stimulation to the superficial radial (SR) nerve were evaluated during forward and backward arm cycling. Irrespective of the cycling direction, background electromyographic (bEMG) and cutaneous reflex patterns were similarly modulated suggesting similar neural control mechanisms for both forward and backward cycling. These bEMG and reflex findings provide further evidence of contributions from CPG activity to the neural regulation of rhythmic arm movement. Second, bEMG and cutaneous reflex (SR nerve) modulation were evaluated during three dissimilar bilateral rhythmic arm cycling tasks created by unilaterally manipulating crank length (CL). The neural regulation of arm cycling was shown to be insensitive to asymmetrical changes in arm crank length suggesting that the neural control was equivalent across the three dissimilar rhythmic arm cycling tasks and that differences in peripherally generated inputs between the dissimilar rhythmic tasks had limited effect on the neural control. Third, the neural control of arm movements was evaluated between those with unstable shoulders and control participants. The alterations of bEMG and the cutaneous reflex patterns suggest that the neural control is compromised in those with shoulder instabilities during rhythmic arm movement. Fourth, inhibition of the soleus H-reflex in stationary legs induced by rhythmic arm cycling was shown to be graded with arm cycling frequency. A minimum threshold arm cycling frequency of .8Hz was required to produce a significant interlimb effect. Fifth, the degree of the soleus H-reflex suppression induced by arm cycling was independent of afferent feedback associated with arm cycling at different crank loads. In combination the latter two studies suggest that central motor commands related to the frequency of arm cycling is the major signal responsible for the soleus H-reflex suppression in stationary legs, while afferent feedback related to upper limb loading during arm cycling is not. Collectively, the data contained in this thesis contribute to the evidence suggesting that CPG activity contributes to neural regulation of rhythmic arm movement, alterations in sensory feedback associated with arm cycling have limited influence on the observed reflex modulation and that the neural control can be disrupted in the presence of prolonged orthopaedic injury. Taken together with our previous findings, the current results also suggests that central motor command (e.g. CPGs) for rhythm generation of the rhythmic arm movement is the primary source of the signal responsible for the observed interlimb neural communication.

While the locomotion performance of legged robots over flat terrain or known obstacles has improved over the past few decades, they have yet to equal the performance of their animal counterparts over variable terrain. This work analyzes a multi-legged reduced order model of cockroach locomotion on variable slopes which will be used as an inspiration for a future sprawled posture legged robot. The cockroach is modeled as a point mass, and each leg of the cockroach is modeled as a massless, tangentially rigid, linearly elastic spring attached at the center of mass. All of the springs are actuated to allow changes in energy to the system. This is accomplished by varying the force free length of each leg in a feed-forward manner without reliance on feedback to change the actuation scheme. Fixed points of the model are found using a numerical solver that varies the velocity and phase shift parameters while leaving all other parameters at fixed values selected to match true cockroach motion. Each fixed point is checked for stability and robustness representing how effective the model is at staying on the predetermined gait, and transport cost as a measure of how efficient this gait is. Stable and robust fixed points were successfully found for the range of heading angles encompassing those of representative cockroach motion at each slope. Cockroaches may select the gait used based on stability or efficiency. Thus, additional fixed points were found in combination with a search routine that varies the leg actuation parameters in order to optimize either stability or metabolic efficiency, gaining insights into why cockroaches use the gaits that they do. Optimized fixed points were found based on four different leg functional combination families depending on whether each leg pushes or pulls. Optimized fixed point gaits exist for every incline slope studied between level ground and vertical slopes, at a range of initial heading angles that encompass those typically used by cockroaches. The selected gaits using both a stability based and an efficiency based optimization on the modeled cockroach are very similar. Both are also similar to gaits used by real cockroaches. The forces generated by the model are qualitatively similar to the experimental forces. / Graduation date: 2012

We present a novel control strategy for running which is robust to disturbances, and makes excellent use of passive dynamics for energy economy. The motivation for our control strategy is based on observations of animals, which are able to economically walk and run over varying terrain and ground dynamics. It is well-known that steady-state animal running can be approximated by spring-mass models, but these passive dynamic models describe only steady-state running and are sensitive to disturbances that animals can accommodate. While animals rely on their passive dynamics for energy economy, they also incorporate active control for disturbance rejection. The same approach can be used for spring-mass walking and running, but an active controller is needed that interferes minimally with the passive dynamics of the system. We demonstrate, in simulation, how force control combined with a leg spring stiffness tuned for the desired hopping frequency provides robustness to disturbances on a model for robot hopping, while maintaining the energy economy of a completely passive system during steady-state operation. Our strategy is promising for robotics applications, because there is a clear distinction between the passive dynamic behavior of the model and the active controller, it does not require sensing of the environment, and it is based on a sound theoretical background that is compatible with existing high-level controllers for ideal spring-mass models. / Graduation date: 2012

Zusammenfassung Histomorphometrische Befunde am M. gluteus medius von Pferden ausgewählter deutscher Warmblutrassen - Selektionskriterium für die sportliche Veranlagung? (96 S., 11 Abb., 52 Tab., 131 Lit.) Zur Untersuchung histomorphometrischer Indizes wurden aus dem M. gluteus medius von Warmblut-Pferden ausgewählter deutscher Zuchtgebiete Bioptate entnommen. Insgesamt standen 64 zweijährige Hengste zur Verfügung. Die Biopsien wurden an einem definierten Punkt und bei einer immer gleichen Entnahmetiefe von 5 cm mit der Biopsiekanüle nach BERGSTRÖM (1962) durchgeführt. Eine Auswertung der Muskelproben erfolgte im Hinblick auf die Rassenzugehörigkeit, hinsichtlich Züchtung der Pferde für den Dressur- bzw. Springsport, mit Bezug auf das Körurteil sowie unter Berücksichtigung der Abstammung von verschiedenen väterlichen Blutlinien. Dazu kam die histochemische Methode der sauren Kreuzkombination nach ZIEGAN (1979) zur Anwendung, welche neben den physiologischen auch die biochemischen Eigenschaften der Muskelfasern berücksichtigt. Demzufolge wurde eine Differenzierung in die Fasertypen STO (slow-twitch-oxidative), FTO (fast-twitch-oxidative), Fasern des Intermediärtyps und FTG (fast-twitch-glycolytic) vorgenommen. Für diese Fasertypen wurde die relative Anzahl, die absolute und die relative Faserquerschnittsfläche sowie die Quotienten schnell-/langsam-kontrahierende Fasern (F/S), oxidative/glykolytische (Ox/G) Muskelfasern und FTO/FTG ermittelt. Zwischen Pferden verschiedener deutscher Warmblutrassen ließen sich signifikante Unterschiede im STO- (p< 0,001) und FTO-Faseranteil (p< 0,01) nachweisen. Warmblutpferde Trakehner Abstammung wiesen dabei mit 35,9 % den größten Anteil langsamer Muskelfasern (STO) und mit 33,8 % den geringsten Anteil schnell-kontrahierender, oxidativer Fasern (FTO) auf. Die gegensätzlichen Extremwerte bezüglich dieser beiden Fasertypen nahmen die Pferde des Zuchtgebietes Westfalen ein. Auch die absoluten Faserquerschnittsflächen langsam-kontrahierender Muskelfasern von Pferden verschiedener Rassen waren signifikant (p< 0,05) verschieden. Wiederum nahmen mit 2957 µm2 die Trakehner eine Spitzenposition ein. Im Vergleich der Werte der relativen Faserquerschnittsfläche von Pferden verschiedener Rassen wurde auch ein signifikanter Unterschied bei den FTG-Fasern deutlich (p< 0,01). Dressurpferde besaßen mit 26,6 % einen signifikant (p< 0,05) höheren STO-Faseranteil als Springpferde mit einem Wert von 21,9 %. Umgekehrt verhielt sich der prozentuale FTO-Faseranteil mit 46,7 % bei Spring- und 38,8 % bei Dressurpferden (p< 0,05). Die Werte der relativen Faseranzahl und der relativen Faserfläche wiesen einen Korrelationskoeffizienten von r=0,92 auf. Demzufolge bestanden zwischen Dressur- und Springpferden auch bei der relativen Faserquerschnittsfläche signifikante Unterschiede für STO- (p< 0,05) und FTO-Fasern (p< 0,001). „Gekörte Hengste“ hatten mit 20 % signifikant (p< 0,05) weniger langsam-kontrahierende Muskelfasern als „Nicht gekörte“ Hengste mit 25 %. Auch für die relative Faserquerschnittsfläche traf dieses Verhältnis signifikant (p< 0,05) zu. Es konnte weiterhin gezeigt werden, daß Nachkommen von verschiedenen väterlichen Blutlinien signifikant im STO- (p< 0,01) und FTO-Faseranteil (p< 0,001) sowie bezüglich der relativen Faserquerschnittsfläche von STO- (p< 0,001), FTO- (p< 0,01) und FTG-Fasern (p< 0,05) und hinsichtlich der absoluten Faserfläche der langsamen Muskelfasern (p< 0,05) voneinander abweichen. Aus den Ergebnissen konnten folgende Erkenntnisse gewonnen werden: 1. Die Befunde weisen auf eine enge Abhängigkeit der Muskelfasertypenkomposition des Pferdes von genetischen Faktoren hin. 2. Bereits zwischen Pferden anderer Rassen beobachtete Unterschiede hinsichtlich morphologischer Muskelindizes lassen sich auch bei Pferden verschiedener deutscher Warmblut-Pferderassen aufzeigen. 3. Pferde, die seit mehreren Generationen speziell für eine Nutzung im Springsport gezüchtet worden sind, besitzen einen höheren prozentualen FTO-Faseranteil. Dieser verleiht ihnen wahrscheinlich die Fähigkeit, in der Absprungphase ein enormes Maß an Kraft zu generieren. Dressurpferde haben Arbeit von vergleichsweise niedriger Intensität, aber langer Dauer zu verrichten. Daraus ergibt sich die Möglichkeit, die Muskelbiopsie bereits bei jungen Pferden als Selektionskriterium einzusetzen. 4. Die Ergebnisse der „Gekörten Hengste“ weisen auf eine Selektion zugunsten der Individuen mit hohem FTO- und dementsprechend niedrigem STO-Faseranteil hin, was auf einen Zusammenhang zwischen der Muskelfasertypenzusammensetzung und der Bewegungsqualität eines Pferdes hindeutet. / Summary Histomorphometric findings of the gluteus medius muscle of horses from selected german warm-blooded breeds - selection criterion for athletic ability? (96 p., 11 fig., 52 tables, 131 ref.) For examining the histomorphometric muscle indices biopsies were taken of warm-blooded horses descending from selected German breeds. Biopsies were taken at standardized depth of 5 cm from the left gluteus medius muscle of 64 two-year-old stallions using a BERGSTROEM biopsy needle (1962). Muscle samples were evaluated according to different breeds, the aptitude for dressage or show jumping, the possession of a breeding licence and the derivation of different paternal bloodlines. The histochemical method used was that described by ZIEGAN (1979), which considers the physiological as well as the biochemical properties of muscle fibres. Therefore muscle fibres were distinguished in STO, FTO, fibres of intermediate type and FTG. For these fibre the types relative number, absolute and relative cross-sectional fibre area as well as the quotient fast-/slow-twitch fibers, oxidative/glycolytic muscle fibers and FTO/FTG were determined. Between horses of different German warm-blooded breeds there were significant differences in the percentage of STO (p< 0,001) and FTO-fibres (p< 0,01). Trakehner horses had the highest percentage of slow-twitch fibres with 35,9 %, and the lowest percentage of FTO-fibres with 33,8 %. The other two extremes according to these fibre types occured in Westphalian horses. Absolute cross-sectional STO-fibre areas were also significantly different between horses of different breeds (p< 0,05). Again, the Trakehner horses were in the lead with 2956,89 µm2. Comparing the relative muscle fibre area of differently bred horses, FTG-fibres also turned out to be significantly different (p< 0,01) from each other. Dressage horses had with 26,6 % a significantly higher (p< 0,05) proportion of STO-fibres than show jumping horses with a percentage of 21,9 %. Show jumping horses had a higher percentage of FTO-fibres with 46,7 % than dressage horses with 38,8 % (p< 0,05). Expressing a high correlation of relative number and relative cross-sectional fibre area (r< 0,92), the latter criterion also turned out to be different for STO- (p< 0,05) and FTO-fibres (p< 0,001). Licenced breeding stallions showed a significantly (p< 0,05) lower proportion of slow-twitch fibres with 20 % than stallions without breeding permission with 25 %. This relation also turned out to be significant for the relative fibre area (p< 0,05) . Furthermore it was found that offsprings of different paternal bloodlines differ from one another according to the percentage of STO- (p< 0,01) and FTO-fibres (p< 0,001), according to relative cross-sectional fibre areas of STO- (p< 0,001), FTO- (p< 0,01) and FTG-fibres (p< 0,05) and according to absolute fibre areas of slow-twitch muscle fibres (p< 0,05). These results suggest following conclusions: 1. The findings show a high correlation between muscle fiber type composition and genetic factors in the horse. 2. Earlier observed differences in morphological muscle indices between different races of horses were also evident between horses of different german warm-blooded breeds. 3. Horses, which have been bred specifically for show jumping over numerous generations, possess a higher percentage of FTO-fibres. This probably enables them to generate an enormous amount of power in the moment of take-off. Dressage horses have to perform exercises of comparatively low intensity but long duration. Therefore the muscle biopsy is a usefull selection criterion in young horses. 4. The results from the licenced breeding stallions indicate selection in favour of individuals having a high percentage of FTO- and a low percentage of STO-fibers, which may be related to muscle fibre properties and the locomotor pattern of the horse.

Locomotion is an integral part of a whole range of animal behaviours. The basic rhythm for locomotion in vertebrates has been shown to arise from local networks residing in the spinal cord and these networks are known as central pattern generators (CPG). However, during the locomotion, these centres are constantly interacting with the sensory feedback signals coming from muscles, joints and peripheral skin receptors in order to adapt the stepping or swimming to varying environmental conditions. Conceptual models of vertebrate locomotion have been constructed using mathematical models of locomotor subsystems based on the neurophysiological evidence obtained primarily in the cat and the salamander, an amphibian with a sprawling posture. Such models provide opportunity for studying the key elements in the transition from aquatic to terrestrial locomotion. Several aspects of locomotor control using the cat or the salamander as an animal model have been investigated employing computer simulations and here we use the same approach to address a number of questions or/and hypotheses related to rhythmic locomotion in quadrupeds. Some of the involved questions are, the role of mechanical linkage during deafferented walking, finding inherent stabilities/instabilities of muscle-joint interactions during normal walking and estimating phase dependent controlability of muscle action over joints. Also we investigate limb and body coordination for different gaits, use of side-stepping in front limbs for turning and the role of sensory feedback in gait generation and transitions in salamanders.      This thesis presents the basics of the biologically realistic models of cat and salamander locomotion and summarizes computational methods in modeling quadruped locomotor subsystems such as CPG, limb muscles and sensory pathways. In the case of cat hind limb, we conclude that the mechanical linkages between the legs play a major role in producing the alternating gait. In another experiment we use the model to identify open-loop linear transfer functions between muscle activations and joint angles while ongoing locomotion. We hypothesize that the musculo-skeletal system for locomotion in animals, at least in cats, operates under critically damped condition.      The 3D model of the salamander is successfully used to mimic locomotion on level ground and in water. We compare the walking gait with the trotting gait in simulations. We also found that for turning, the use of side-stepping alone or in combination with trunk bending is more effective than the use of trunk bending alone. The same model together with a more realistic CPG composed of spiking neurons was used to investigate the role of sensory feedback in gait generation and transition. We found that the proprioceptive sensory inputs are essential in obtaining the walking gait, whereas the trotting gait is more under central (CPG) influence compared to that of the peripheral or sensory feedback.      This thesis work sheds light on understanding the neural control mechanisms behind vertebrate locomotion. Additionally, both neuro-mechanical models can be used for further investigations in finding new control algorithms which give robust, adaptive, efficient and realistic stepping in each leg, which would be advantageous since it can be implemented on a controller of a quadruped-robotic device. / This work is Funded by Swedish International Development cooperation Agency (SIDA). QC 20111110

Includes bibliographical references (leaves 276-2970. / xiii, 297 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigations presented involve 18 hour to 5 day old South Australian merino lambs. Some twin lambs were available for comparative studies. Examines the relationship between the strength of ewe-lamb bond and the lamb's ability to follow the mother, the energy availability and usage in the lamb, particularly for locomotion, and the metabolic and cardiorespiratory responses to locomotion. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Sciences, 1992