Motor Coordination Behavior Research Articles

Preconditioning of exosomes derived from human olfactory ensheathing cells improved motor coordination and balance in an SCA3/MJD mouse model: A new therapeutic approach

Exosome therapy is a novel trend in regeneration medicine. However, identifying a suitable biomarker that can associate the therapeutic efficacy of exosomes with SCA3/MJD is essential. In this study, parental cells were preconditioned with butylidenephthalide (Bdph) for exosome preparation to evaluate the therapeutic effect of SCA3/MJD. The therapeutic agent hsa-miRNA-6780–5p was enriched up to 98-fold in exosomes derived from butylidenephthalide (Bdph)-preconditioned human olfactory ensheathing cells (hOECs) compared with that in naïve hOECs exosomes. The particle sizes of exosomes derived from naïve hOECs and those derived from hOECs preconditioned with Bdph were approximately 113.0 ± 3.5 nm and 128.9 ± 0.7 nm, respectively. A liposome system was used to demonstrate the role of hsa-miRNA-6780–5p, wherein hsa-miRNA-6780–5p was found to enhance autophagy and inhibit the expression of spinocerebellar ataxia type 3 (SCA3) disease proteins with the polyglutamine (polyQ) tract. Exosomes with enriched hsa-miRNA-6780–5p were further applied to HEK-293–84Q cells, leading to decreased expression of polyQ and increased autophagy. The results were reversed when 3MA, an autophagy inhibitor, was added to the cells treated with hsa-miRNA-6780–5p-enriched exosomes, indicating that the decreased polyQ expression was modulated via autophagy. SCA3 mice showed improved motor coordination behavior when they intracranially received exosomes enriched with hsa-miRNA-6780–5p. SCA3 mouse cerebellar tissues treated with hsa-miRNA-6780–5p-enriched exosomes showed decreased expression of polyQ and increased expression of LC3II/I, an autophagy marker. In conclusion, our findings can serve as a basis for developing an alternative therapeutic strategy for SCA3 disease treatment using miRNA-enriched exosomes derived from chemically preconditioned cells.

Genetic Deletion of Thorase Causes Purkinje Cell Loss and Impaired Motor Coordination Behavior.

Thorase belongs to the AAA+ ATPase family, which plays a critical role in maintaining cellular homeostasis. Our previous work reported that Thorase was highly expressed in brain tissue, especially in the cerebellum. However, the roles of Thorase in the cerebellum have still not been characterized. In this study, we generated conditional knockout mice (cKO) with Thorase deletion in Purkinje cells. Thorase cKO mice exhibited cerebellar degenerative diseases-like behavior and significant impairment in motor coordination. Thorase deletion resulted in more Purkinje neuron apoptosis, leading to Purkinje cell loss in the cerebellum of Thorase cKO mice. We also found enhanced expression of the inflammatory protein ASC, IL-1β, IL-6 and TNF-α in the Thorase cKO cerebellum, which contributed to the pathogenesis of cerebellar degenerative disease. Our findings provide a better understanding of the role of Thorase in the cerebellum, which is a theoretical basis for Thorase as a therapeutic drug target for neurodegenerative diseases.

Additional polgD257A mutation (mutator) does not influence dopaminergic neurodegeneration in aged parkin-deficient mice

Background: Parkinson’s disease is a neurodegenerative disease caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Among the first identified causes of autosomal recessive Parkinson’s disease were mutations in the parkin gene. Independently, we and other groups have developed various parkin knockout mice, and none displayed dopaminergic degeneration in the substantia nigra. Interestingly, dopaminergic degeneration in the substantia nigra has been reported in a parkin knockout line (exon 3 deletion) carrying an additional mutation (D257A) in the mitochondrial DNA polymerase (polg) gene (mutator). The mutator mice show accelerated mutation rates in mitochondrial DNA resulting in a premature-aging phenotype. Methods: To verify this finding, we crossed our parkin-deficient mice with the mutator mice, and characterized phenotypic changes of the parkin/mutator double mutant mice up to one year of age. We examined their locomotion and motor coordination behaviors by using the open field, the rotarod, and the pole test, subsequently investigating their nigrostriatal axis by counting TH-positive cells in every tenth section throughout the entire substantia nigra pas compacta and their termini in the striatum. Results: The double mutants did not display additional deficiencies in locomotion in our behavior tests. We could also not detect dopaminergic neurodegeneration in the substantia nigra pars compacta of aged double mutants measured by levels of tyrosine hydroxylase positive neurons in the substantia nigra pars compacta as well as in striatal terminals. Conclusion: Our results do not support the hypothesis that the polgD257A mutation contributes to the age-related vulnerability of dopaminergic neurons in parkin-deficient mice. Keywords: Parkin, neurodegeneration, polgD257A, mutator, substantia nigra

Nrf2/HO-1 Signaling Activator Acetyl-11-keto-beta Boswellic Acid (AKBA)-Mediated Neuroprotection in Methyl Mercury-Induced Experimental Model of ALS.

Methylmercury (MeHg) is a potent neurotoxin that causes neurotoxicity and neuronal cell death. MeHg exposure also leads to oligodendrocyte destruction, glial cell overactivation, and demyelination of motor neurons in the motor cortex and spinal cord. As a result, MeHg plays an important role in the progression of amyotrophic lateral sclerosis (ALS)-like neurocomplications. ALS is a fatal neurodegenerative disorder in which neuroinflammation is the leading cause of further CNS demyelination. Nuclear factorerythroid-2-related factor-2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling pathway was thought to be a potential target for neuroprotection in ALS. Acetyl-11-keto-beta-boswellic acid (AKBA) is a multi-component pentacyclic triterpenoid mixture derived from Boswellia serrata with anti-inflammatory and antioxidant properties. The research aimed to investigate whether AKBA, as a Nrf2 / HO-1 activator, can provide protection against ALS. Thus, we explored the role of AKBA on the Nrf2/HO-1 signaling pathway in a MeHg-induced experimental ALS model. In this study, ALS was induced in Wistar rats by oral gavage of MeHg 5mg/kg for 21days. An open field test, force swim test, and grip strength were performed to observe experimental rats' motor coordination behaviors. In contrast, a morris water maze was performed for learning and memory. Administration of AKBA 50mg/kg and AKBA 100mg/kg continued from day 22 to 42. Neurochemical parameters were evaluated in the rat's brain homogenate. In the meantime, post-treatment with AKBA significantly improved behavioral, neurochemical, and gross pathological characteristics in the brain of rats by increasing the amount of Nrf2/HO-1 in brain tissue. Collectively, our findings indicated that AKBA could potentially avoid demyelination and encourage remyelination.

Testosterone enhances mitochondrial complex V function in the substantia nigra of aged male rats.

Deficits in coordinated motor behavior and mitochondrial complex V activity have been observed in aged males. Testosterone supplementation can improve coordinated motor behavior in aged males. We investigated the effects of testosterone supplementation on mitochondrial complex V function in the substantia nigra (a brain region that regulates motor activity) in aged male rats. These rats exhibited diminished ATP levels, attenuated mitochondrial complex V activity, and reduced expression of 3 of the 17 mitochondrial complex V subunits (ATP6, ATP8 and ATP5C1) in the substantia nigra. Testosterone supplementation increased ATP levels, mitochondrial complex V activity, and ATP6, ATP8 and ATP5C1 expression in the substantia nigra of the rats. Conversely, orchiectomy reduced mitochondrial complex V activity, downregulated ATP6 and ATP8 expression, and upregulated ATP5C1, ATP5I and ATP5L expression in the substantia nigra. Testosterone replacement reversed those effects. Thus, testosterone enhanced mitochondrial complex V function in the substantia nigra of aged male rats by upregulating ATP6 and ATP8. As potential testosterone targets, these two subunits may to some degree maintain nigrostriatal dopaminergic function in aged males.

Study of anxiolytic and motor co-ordination activity of Cucurbita moschata and its possible mechanism through GABA receptors

PurposeTo evaluate anxiolytic and motor coordination activity of ethanolic and ethyl acetate extracts of Cucurbita moschata seeds (CM) in mice. MethodSeeds were dried, powdered and extracted in two different solvents, one is ethanol and other is ethyl acetate. The extracts were orally administered in mice for fourteen days followed by testing in Elevated plus Maze (EPM) and Light Dark Box (LDB) for studying the anxiolytic behaviour and the rota rod was used to check the motor coordination behaviour. ResultBoth extracts showed prominent anxiolytic activity but ethanolic extract of Cucurbita moschata seeds (EECM) (200 mg/kg) showed best result which was comparable to standard drug Alprazolam in both the models. Moreover, an alteration was seen in motor coordination by the ethanolic extract at a dose of 200 mg/kg in contrast to group I mice. The mechanism was explored using Flumazenil drug, which proposed that the extract may increase chloride ion influx that was blocked by co-administration of negative allosteric modulator, flumazenil, suggesting a GABAA receptor mediated mechanism of action. ConclusionTaken altogether, the present study demonstrates that both the extracts of Cucurbita moschata has shown a good anxiolytic & motor coordination activity proving the proposed study as factual.

To walk or to run - a question of movement attractor stability.

During locomotion, humans change gait mode between walking and running as locomotion speed is either increased or decreased. Dynamical systems theory predicts that the self-organization of coordinated motor behaviors dictates the transition from one distinct stable attractor behavior to another distinct attractor behavior (e.g. walk to run or vice versa) as the speed is changed. To evaluate this prediction, the present study investigated the attractor stability of walking and running across a range of speeds evoking both self-selected gait mode and non-self-selected gait mode. Eleven subjects completed treadmill walking for 3 min at 0.89, 1.12, 1.34, 1.56, 1.79, 2.01, 2.24 and 2.46 m s-1 and running for 3 min at 1.79, 2.01, 2.24, 2.46, 2.68, 2.91, 3.13 and 3.35 m s-1 in randomized order while lower limb joint angles and sacrum displacements was recorded. Attractor stability was quantified by continuous relative phase and deviation phase of lower limb segment angles, and the largest Lyapunov exponent, correlation dimension and movement variability of the sacrum marker displacement and the hip, knee and ankle joint angles. Lower limb attractor stability during walking was maximized at speeds close to the self-selected preferred walking speed and increased during running as speed was increased. Furthermore, lower limb attractor stability was highest at a particular gait mode closest to the corresponding preferred speed, in support of the prediction of dynamical systems theory. This was not the case for the sacrum displacement attractor, suggesting that lower limb attractor behavior provides a more appropriate order parameter compared with sacrum displacement.

Anticonvulsant Potential of Dichloromethane Extract of Aspilia africana Leaf in Mice

Aim: The study was carried out to determine the anticonvulsant potential of dichloromethane leaf extract of Aspilia africana.
 Study Design: Three seizure models namely: Pentylenetetrazole (PTZ), strychnine (STC) and maximal electroshock (MES) were used, motor coordination behavior of the animals were also assessed.
 Place and Duration of Study: The study was carried out between the months of October and November, 2017 at Pharmacology laboratory, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Niger Delta University, Bayelsa State, Nigeria.
 Methodology: The powdered leaves of A. africana (2000 g) were extracted with 10 liters of 100% dichloromethane. Doses of 25, 50, 100 and 200 mg/kg were administered to the test animals.
 Results: The chemical models, STC & PTZ showed 50% & 100% survival respectively. The delayed onset of seizure suggested anti-seizure potential of dichloromethane extract of A. Africana leaf with the maximal latency period of seizure recorded in the 25 mg/kg dose within the following chemical models, this was significant, P = .05 compared to the normal control. The MES method showed that at doses of 25 & 50, 100 mg/kg, the animals were 66.7% & 50% free of hind limb tonic extension (HLTE). Furthermore, there was reduced motor coordination potential at 25 mg/kg by 68.5%, which was significant at the level of, P = .05, compared to healthy control. 
 Conclusion: From the preceding, it can be seen that the dichloromethane leaf extract of A. Africana has antiseizure potential.

Faster emergence behavior from ketamine/xylazine anesthesia with atipamezole versus yohimbine.

Recent interest in reversal of the hypnotic effects of anesthesia has mainly focused on overcoming a surge in GABA-mediated inhibitory signaling through activation of subcortical arousal circuits or antagonizing GABA receptors. Here we examine the reversal of anesthesia produced from non-GABA agents ketamine/xylazine and the effects of antagonists of adrenoreceptors. These antagonists vary in selectivity and produce temporally unique waking behavior post-anesthesia. We compared two antagonists with differential selectivity for α1- vs. α2-receptors, yohimbine (YOH, 1:40 selectivity) and atipamezole (ATI, 1:8500). Adult mice received intraperitoneal injections of either YOH (4.3 mg/kg), ATI (0.4 mg/kg), or saline after achieving sustained loss of righting following injection of ketamine/xylazine (ketamine: 65.0 mg/kg; xylazine: 9.9 mg/kg). Behaviors indicative of the post-anesthesia, re-animation sequence were carefully monitored and the timing of each behavior relative to anesthesia induction was compared. Both YOH and ATI hastened behaviors indicative of emergence, but ATI was faster than YOH to produce certain behaviors, including whisker movement (YOH: 21.9±1.5 min, ATI: 17.5±0.5 min, p = 0.004) and return of righting reflex (RORR) (YOH: 40.6±8.8 min, ATI: 26.0±1.2 min, p<0.001). Interestingly, although YOH administration hastened early behavioral markers of emergence relative to saline (whisking), the completion of the emergence sequence (time from first marker to appearance of RORR) was delayed with YOH. We attribute this effect to antagonism of α1 receptors by yohimbine. Also notable was the failure of either antagonist to hasten the re-establishment of coordinated motor behavior (e.g., attempts to remove adhesive tape on the forepaw placed during anesthesia) relative to the end of emergence (RORR). In total, our work suggests that in addition to pharmacokinetic effects, re-establishment of normal waking behaviors after anesthesia involves neuronal circuits dependent on time and/or activity.

Potentiation of motor sub-networks for motor control but not working memory: Interaction of dACC and SMA revealed by resting-state directed functional connectivity.

The dorsal Anterior Cingulate Cortex (dACC) and the Supplementary Motor Area (SMA) are known to interact during motor coordination behavior. We previously discovered that the directional influences underlying this interaction in a visuo-motor coordination task are asymmetric, with the dACC→SMA influence being significantly greater than that in the reverse direction. To assess the specificity of this effect, here we undertook an analysis of the interaction between dACC and SMA in two distinct contexts. In addition to the motor coordination task, we also assessed these effects during a (n-back) working memory task. We applied directed functional connectivity analysis to these two task paradigms, and also to the rest condition of each paradigm, in which rest blocks were interspersed with task blocks. We report here that the previously known asymmetric interaction between dACC and SMA, with dACC→SMA dominating, was significantly larger in the motor coordination task than the memory task. Moreover the asymmetry between dACC and SMA was reversed during the rest condition of the motor coordination task, but not of the working memory task. In sum, the dACC→SMA influence was significantly greater in the motor task than the memory task condition, and the SMA→dACC influence was significantly greater in the motor rest than the memory rest condition. We interpret these results as suggesting that the potentiation of motor sub-networks during the motor rest condition supports the motor control of SMA by dACC during the active motor task condition.

Neuronal Correlates of Functional Coupling between Reach- and Grasp-Related Components of Muscle Activity.

Coordinated reach-to-grasp movements require precise spatiotemporal synchrony between proximal forelimb muscles (shoulder, elbow) that transport the hand toward a target during reach, and distal muscles (wrist, digit) that simultaneously preshape and orient the hand for grasp. The precise mechanisms through which the redundant neuromuscular circuitry coordinates reach with grasp, however, remain unclear. Recently, Geed and Van Kan (2016) demonstrated, using exploratory factor analysis (EFA), that limited numbers of global, template-like transport/preshape- and grasp-related muscle components underlie the complexity and variability of intramuscular electromyograms (EMGs) of up to 21 distal and proximal muscles recorded while monkeys performed reach-to-grasp tasks. Importantly, transport/preshape- and grasp-related muscle components showed invariant spatiotemporal coupling, which provides a potential mechanism for coordinating forelimb muscles during reach-to-grasp movements. In the present study, we tested whether ensemble discharges of forelimb neurons in the cerebellar nucleus interpositus (NI) and its target, the magnocellular red nucleus (RNm), a source of rubrospinal fibers, function as neuronal correlates of the transport/preshape- and grasp-related muscle components we identified. EFA applied to single-unit discharges of populations of NI and RNm neurons recorded while the same monkeys that were used previously performed the same reach-to-grasp tasks, revealed neuronal components in the ensemble discharges of both NI and RNm neuronal populations with characteristics broadly similar to muscle components. Subsets of NI and RNm neuronal components were strongly and significantly crosscorrelated with subsets of muscle components, suggesting that similar functional units of reach-to-grasp behavior are expressed by NI and RNm neuronal populations and forelimb muscles. Importantly, like transport/preshape- and grasp-related muscle components, their NI and RNm neuronal correlates showed invariant spatiotemporal coupling. Clinical and lesion studies have reported disruption of coupling between reach and grasp following cerebellar damage; the present results expand on those studies by identifying a neuronal mechanism that may underlie cerebellar contributions to spatiotemporal coordination of distal and proximal limb muscles during reaching to grasp. We conclude that finding similar functional units of behavior expressed at multiple levels of information processing along interposito-rubrospinal pathways and forelimb muscles supports the hypothesis that functionally related populations of NI and RNm neurons act synergistically in the control of complex coordinated motor behaviors.

Effects of experimentally manipulated yolk thyroid hormone levels on offspring development in a wild bird species

Maternal effects are a crucial mechanism in a wide array of taxa to generate phenotypic variation, thereby affecting offspring development and fitness. Maternally derived thyroid hormones (THs) are known to be essential for offspring development in mammalian and fish models, but have been largely neglected in avian studies, especially in respect to natural variation and an ecological context. We studied, for the first time in a wild species and population, the effects of maternally derived THs on offspring development, behavior, physiology and fitness-related traits by experimental elevation of thyroxine and triiodothyronine in ovo within the physiological range in great tits (Parus major). We found that elevated yolk TH levels had a sex-specific effect on growth, increasing male and decreasing female growth, relative to controls, and this effect was similar throughout the nestling period. Hatching or fledging success, motor coordination behavior, stress reactivity and resting metabolic rate were not affected by the TH treatment. We conclude that natural variation in maternally derived THs may affect some offspring traits in a wild species. As this is the first study on yolk thyroid hormones in a wild species and population, more such studies are needed to investigate its effects on pre-hatching development, and juvenile and adult fitness before generalizations on the importance of maternally derived yolk thyroid hormones can be made. However, this opens a new, interesting avenue for further research in the field of hormone mediated maternal effects.

Deficits in coordinated motor behavior and in nigrostriatal dopaminergic system ameliorated and VMAT2 expression up-regulated in aged male rats by administration of testosterone propionate

The effects of testosterone propionate (TP) supplements on the coordinated motor behavior and nigrostriatal dopaminergic (NSDA) system were analyzed in aged male rats. The present study showed the coordinated motor behavioral deficits, the reduced activity of NSDA system and the decreased expression of vesicular monoamine transporter 2 (VMAT2) in 24month-old male rats. Long term TP treatment improved the motor coordination dysfunction with aging. Increased tyrosine hydroxylase and dopamine transporter, as well as dopamine and its metabolites were found in the NSDA system of TP-treated 24month-old male rats, indicative of the amelioratory effects of TP supplements on NSDA system of aged male rats. The enhancement of dopaminergic (DAergic) activity of NSDA system by TP supplements might underlie the amelioration of the coordinated motor dysfunction in aged male rats. TP supplements up-regulated VMAT2 expression in NSDA system of aged male rats. Up-regulation of VMAT2 expression in aged male rats following chronic TP treatment might be involved in the maintenance of DAergic function of NSDA system in aged male rats.

Bicycling and Walking are Associated with Different Cortical Oscillatory Dynamics.

Although bicycling and walking involve similar complex coordinated movements, surprisingly Parkinson’s patients with freezing of gait typically remain able to bicycle despite severe difficulties in walking. This observation suggests functional differences in the motor networks subserving bicycling and walking. However, a direct comparison of brain activity related to bicycling and walking has never been performed, neither in healthy participants nor in patients. Such a comparison could potentially help elucidating the cortical involvement in motor control and the mechanisms through which bicycling ability may be preserved in patients with freezing of gait. The aim of this study was to contrast the cortical oscillatory dynamics involved in bicycling and walking in healthy participants. To this end, EEG and EMG data of 14 healthy participants were analyzed, who cycled on a stationary bicycle at a slow cadence of 40 revolutions per minute (rpm) and walked at 40 strides per minute (spm), respectively. Relative to walking, bicycling was associated with a stronger power decrease in the high beta band (23–35 Hz) during movement initiation and execution, followed by a stronger beta power increase after movement termination. Walking, on the other hand, was characterized by a stronger and persisting alpha power (8–12 Hz) decrease. Both bicycling and walking exhibited movement cycle-dependent power modulation in the 24–40 Hz range that was correlated with EMG activity. This modulation was significantly stronger in walking. The present findings reveal differential cortical oscillatory dynamics in motor control for two types of complex coordinated motor behavior, i.e., bicycling and walking. Bicycling was associated with a stronger sustained cortical activation as indicated by the stronger high beta power decrease during movement execution and less cortical motor control within the movement cycle. We speculate this to be due to the more continuous nature of bicycling demanding less phase-dependent sensory processing and motor planning, as opposed to walking.

Neuroprotecitve effect of NPY in in vitro models of Alzheimer's disease, focus on neurotrophins

neurodegenerative disorder associated with an expanded polyglutamine tract within the ataxin-3 protein, and characterized by progressive impairment of motor coordination, associated to neurodegeneration of specific brain regions including cerebellum and striatum. The currently available therapies do not allow modification of disease progression. NPY has been shown to exert potent neuroprotective effects by multiple pathways associated to the MJD mechanisms of disease. Thus, we evaluated NPY levels in MJD and investigated whether raising NPY by gene transfer would alleviate neuropathological and behavioural deficits in cerebellar and striatal mouse models of the disease. For that, a cerebellar transgenic and a striatal lentiviral-based models of MJD were used. NPY overexpression in the affected brain regions in these two mouse models was obtained by stereotaxic injection of adeno-associated viral vectors encoding NPY; 8 weeks after viral injection, balance and motor coordination behaviour and neuropathology were analysed. NPY levels were decreased in two MJD patients' cerebella and in striata and cerebella of disease mouse models. Furthermore, NPY overexpression alleviated motor coordination impairments and attenuated related neuropathological cerebellar parameters and decreasing mutant ataxin-3 aggregation. Additionally, NPY mediated increase of brain-derived neurotrophic factor levels and decreased neuroinflammation markers. Our data suggest that NPY is a potential therapeutic strategy for MJD. This work was supported by The Richard Chin and Lily Lock Research Fund; E-Rare4/0003/2012; FCT SFRH/BD/74993/2010, SFRH/BD/87404/ 2012, SRFH/BPD/87341/2012; QREN – Projeto Mais Centro – New Strategies to Manage Brain Diseases CENTRO-07-ST24-FEDER-002002, FEDER and COMPETE – UID/NEU/04539/2013.

Bimodal Respiratory-Locomotor Neurons in the Neonatal Rat Spinal Cord.

Neural networks that can generate rhythmic motor output in the absence of sensory feedback, commonly called central pattern generators (CPGs), are involved in many vital functions such as locomotion or respiration. In certain circumstances, these neural networks must interact to produce coordinated motor behavior adapted to environmental constraints and to satisfy the basic needs of an organism. In this context, we recently reported the existence of an ascending excitatory influence from lumbar locomotor CPG circuitry to the medullary respiratory networks that is able to depolarize neurons of the parafacial respiratory group during fictive locomotion and to subsequently induce an increased respiratory rhythmicity (Le Gal et al., 2014b). Here, using an isolated in vitro brainstem-spinal cord preparation from neonatal rat in which the respiratory and the locomotor networks remain intact, we show that during fictive locomotion induced either pharmacologically or by sacrocaudal afferent stimulation, the activity of both thoracolumbar expiratory motoneurons and interneurons is rhythmically modulated with the locomotor activity. Completely absent in spinal inspiratory cells, this rhythmic pattern is highly correlated with the hindlimb ipsilateral flexor activities. Furthermore, silencing brainstem neural circuits by pharmacological manipulation revealed that this locomotor-related drive to expiratory motoneurons is solely dependent on propriospinal pathways. Together these data provide the first evidence in the newborn rat spinal cord for the existence of bimodal respiratory-locomotor motoneurons and interneurons onto which both central efferent expiratory and locomotor drives converge, presumably facilitating the coordination between the rhythmogenic networks responsible for two different motor functions. Significance statement: In freely moving animals, distant regions of the brain and spinal cord controlling distinct motor acts must interact to produce the best adapted behavioral response to environmental constraints. In this context, it is well established that locomotion and respiration must to be tightly coordinated to reduce muscular interferences and facilitate breathing rate acceleration during exercise. Here, using electrophysiological recordings in an isolated in vitro brainstem-spinal cord preparation from neonatal rat, we report that the locomotor-related signal produced by the lumbar central pattern generator for locomotion selectively modulates the intracellular activity of spinal respiratory neurons engaged in expiration. Our results thus contribute to our understanding of the cellular bases for coordinating the rhythmic neural circuitry responsible for different behaviors.

Binocular Perception of 2D Lateral Motion and Guidance of Coordinated Motor Behavior.

Zannoli, Cass, Alais, and Mamassian (2012) found greater audiovisual lag between a tone and disparity-defined stimuli moving laterally (90-170 ms) than for disparity-defined stimuli moving in depth or luminance-defined stimuli moving laterally or in depth (50-60 ms). We tested if this increased lag presents an impediment to visually guided coordination with laterally moving objects. Participants used a joystick to move a virtual object in several constant relative phases with a laterally oscillating stimulus. Both the participant-controlled object and the target object were presented using a disparity-defined display that yielded information through changes in disparity over time (CDOT) or using a luminance-defined display that additionally provided information through monocular motion and interocular velocity differences (IOVD). Performance was comparable for both disparity-defined and luminance-defined displays in all relative phases. This suggests that, despite lag, perception of lateral motion through CDOT is generally sufficient to guide coordinated motor behavior.

Neuropeptide Y mitigates neuropathology and motor deficits in mouse models of Machado-Joseph disease.

Machado-Joseph disease (MJD) is a fatal, dominantly inherited neurodegenerative disorder associated with an expanded polyglutamine tract within the ataxin-3 protein, and characterized by progressive impairment of motor coordination, associated with neurodegeneration of specific brain regions, including cerebellum and striatum. The currently available therapies do not allow modification of disease progression. Neuropeptide Y (NPY) has been shown to exert potent neuroprotective effects by multiple pathways associated with the MJD mechanisms of disease. Thus, we evaluated NPY levels in MJD and investigated whether raising NPY by gene transfer would alleviate neuropathological and behavioural deficits in cerebellar and striatal mouse models of the disease. For that, a cerebellar transgenic and a striatal lentiviral-based models of MJD were used. NPY overexpression in the affected brain regions in these two mouse models was obtained by stereotaxic injection of adeno-associated viral vectors encoding NPY. Up to 8 weeks after viral injection, balance and motor coordination behaviour and neuropathology were analysed. We observed that NPY levels were decreased in two MJD patients' cerebella and in striata and cerebella of disease mouse models. Furthermore, overexpression of NPY alleviated the motor coordination impairments and attenuated the related neuropathological parameters, preserving cerebellar volume and granular layer thickness, reducing striatal lesion and decreasing mutant ataxin-3 aggregation. Additionally, NPY mediated increase of brain-derived neurotrophic factor levels and decreased neuroinflammation markers. Our data suggest that NPY is a potential therapeutic strategy for MJD.

Can Real-Time, Adaptive Human–Robot Motor Coordination Improve Humans’ Overall Perception of a Robot?

Previous research on social interaction among humans suggested that interpersonal motor coordination can help to establish social rapport. Our research addresses the question of whether, in a human–humanoid interaction experiment, the human’s overall perception of a robot can be improved by realizing motor coordination behavior that allows the robot to adapt in real-time to a person’s behavior. A synchrony detection method using information distance was adopted to realize the real-time human–robot motor coordination behavior, which guided the humanoid robot to coordinate its movements to a human by measuring the behavior synchrony between the robot and the human. The feedback of the participants indicated that most of the participants preferred to interact with the humanoid robot with the adaptive motor coordination capability. The results of this proof-of-concept study suggest that the motor coordination mechanism improved humans’ overall perception of the humanoid robot. Together with our previous findings, namely that humans actively coordinate their behaviors to a humanoid robot’s behaviors, this study further supports the hypothesis that bidirectional motor coordination could be a valid approach to facilitate adaptive human–humanoid interaction.

The spino-bulbar-cerebellar pathway: organization and neurochemical properties of spinal cells that project to the lateral reticular nucleus in the rat.

In addition to classical spinocerebellar pathways, the cerebellum receives information from the spinal cord indirectly via spino-bulbar-cerebellar systems. One of the structures in this pathway is the lateral reticular nucleus (LRt). We performed series of experiments to investigate the organization and neurotransmitter content of spinoreticular tract (SRT) neurons in the lumbar spinal cord that project to the LRt. Three rats received injections of the b subunit of Cholera toxin (CTb) or Fluorogold (FG) within the left and right LRt. The majority of SRT cells (56–61%) were found within the contralateral medial intermediate gray matter where small numbers (7–10%) of double-labeled cells were also present on both sides of the cord. Six rats received unilateral spinal injections of CTb to label spinal projections to the LRt. Injections of FG were made also into the anterior lobe of the cerebellum to label LRt pre-cerebellar neurons. Terminals were found mainly ipsilateral to spinal injection sites within the central and ventrolateral regions of the LRt. Immunocytochemical analysis of SRT terminals revealed that the majority (75%) were contained vesicular glutamate transporter 2 but a minority (20%) contained the vesicular GABA transporter. The inhibitory subpopulation was found to be GABAergic, glycinergic, or contained both transmitters. Inhibitory and excitatory terminals were present within overlapping regions of the nucleus. Most CTb terminals contacting LRt pre-cerebellar neurons were excitatory (80%) whereas a minority were inhibitory and most cells (88%) received contacts from both inhibitory and excitatory terminals. This study shows that SRT axons in the LRt have the capacity to exert direct excitatory and inhibitory actions on LRt pre-cerebellar neurons. Thus spinal cord input has the capacity to facilitate or depress the activity of individual LRt cells which in turn adjust activity in the cerebellum to produce coordinated motor behaviors.