L'excitabilité est une propriété bien connue des neurones biologiques. Il s'agit d'une réponse de type tout-ou-rien à une perturbation au delà d'un seuil caractéristique appelé seuil excitable. D'autres propriétés importantes existent dans les neurones comme les périodes réfractaires et la sommation temporelle ou spatiale de stimuli d'entrée.L'excitabilité a été étudiée dans certains composants actifs à semiconducteur et notamment les composants à semiconducteurs III-V. Leurs propriétés neuro-mimétiques pourraient permettre de traiter l'information de façon tout-optique avec une grande bande passante et une faible consommation.Grâce aux nouvelles techniques de micro-nano fabrication, il est devenu possible de fabriquer des micropiliers lasers à absorbant saturable. Ces micropiliers pourraient permettre la réalisation de réseaux de micropiliers couplés excitables analogues à des réseaux de neurones photoniques.Dans cette thèse j'ai étudié les propriétés neuro-mimétiques de micropiliers lasers à absorbant saturable intégré. Les principaux résultats de cette thèse sont les suivants : 1) la technique de fabrication des micropiliers a été améliorée conduisant à une augmentation de leur durée de vie et une diminution du seuil laser. 2) des propriétés de base des neurones biologiques, comme l'excitabilité, l'existence des périodes réfractaires, la sommation temporelle, ont été mises en évidence expérimentalement et analysées à l'aide du modèle de Yamada. 3) des effets de propagation d'excitations ont été démontrés dans des structures unidimensionnelles : des lasers ligne et des chaînes de micropiliers couplés.La démonstration des propriétés neuromimétiques de micropiliers lasers à absorbant saturable et la mise en évidence de la propagation d'excitations ouvrent la voie à la réalisation de réseaux de micropiliers couplés pour les traitements neuromimétiques des signaux qui pourront être exploités pour de la logique codée à l'aide de pics excitables ainsi que pour du stockage d'information dans des circuits mémoires tout-optiques. / Excitability is a well known property of biological neurons. In excitable systems, the response to a perturbation above the excitable threshold is of all-or-none type. Other properties exist in neurons such as the refractory periods and temporal or spatial summation of input stimuli.Excitability has been demonstrated in many III-V semiconductor material devices. Thanks to their nonlinear properties it could be possible to realize neuromimetic and all-optical signal processing with high speed and low energy consumption. Thanks to progress in fabrication techniques it is possible to fabricate high quality micropillar laser with saturable absorber. Thus, using micropillars it could be possible to realize neural photonic networks analog to neural networks.In this thesis work, I studied neuron-like properties of a micropillar laser with a saturable absorber. My main results are : 1) fabrication of micropillars has been improved leading to an increase of their robustness and a reduction of the laser threshold. 2) well known properties of biological neurons, such as excitability, existence of refractory periods, temporal summation, have been demonstrated experimentally and have been numerically analyzed with the Yamada model. 3) propagation effects of excitations have been demonstrated in one-dimensional structures : wire lasers and chains of coupled micropillars.The demonstration of neuromimetic properties in micropillar lasers with saturable absorber and the evidence of propagation of excitations pave the way to neuromorphic networks based on coupled micropillars for neuromimetic signal processing like information encoding with excitable pulses and realization of optical memories.

Many neurological disorders are a result of widespread changes in the excitability of brain tissue. The specific changes in neuronal excitability produces or worsens many of the symptoms associated with these disorders. Pharmacological methods are effective, but their associated side-effects are substantial, and often approximate the severity of the symptoms of the original disorder. The ketogenic diet, a high-fat, low-carbohydrate diet, has been shown to improve many neurological diseases by reducing hyperexcitability without the aforementioned side effects. The current study tested the hypothesis that a ketogenic diet would be associated with alterations in cerebral excitability. Animals were fed either a control or ketogenic diet for at least 21 days prior to experimentation. Power spectral analysis was conducted using EEG data across frequency bands, and compared between diet groups. Current source density analysis was also performed to visualize potential alterations in cerebral excitability.. In the second part of the experiment, a non-invasive ischemic stroke was delivered, and the excitability of the contralateral cortex was monitored. No significant differences were observed between ketogenic and control experiments in regards to overall excitability, although ketogenic diet experiments showed a significantly higher number of acute EEG depressions. No cortical spreading depression events were observed in contralateral recordings. Our findings are in contrast with data showing that ketogenic diets change overall basal excitability, but are in concert with other studies that show that ketogenic diets may not be associated with changes in excitability, but in changes in neuroplasticity.

The aim of the present thesis was to investigate the relationship between individuals' allocation of overt visual attention during action observation and their consequent pickup of information. Four interrelated studies were conducted to achieve this. In Study 1 we examined the effects of visual guidance - colour highlighting of relevant aspects of the action - on observational learning of the golf swing. The results showed that the visual guides facilitated novices' intake of information pertaining to the model's posture, which was reflected in faster learning. In the remaining studies, transcranial magnetic stimulation and eye tracking data were acquired concurrently to measure the interaction between gaze behaviour and motor resonance - a neurophysiological index of the motor system's engagement with a viewed action, and thus a correlate of information extraction. In Study 2, we directed observers' gaze to distinct locations of the display while they viewed thumb adduction/abduction movements. The results showed that, by directing gaze to a location that maximised the amount of thumb motion across the fovea, motor resonance was maximised relative to a free viewing condition. In Study 3 we examined the link between gaze and motor resonance during the observation of transitive actions. Participants viewed reach-to-grasp actions with natural gaze, or while looking at a target- or an effector- based visual guide. The results showed that the effector-based guide disrupted natural gaze behaviour, and this was associated with a reversal of the motor resonance response. In Study 4 we showed novice and skilled golfers videos of the golf swing and of a reach-grasp-lift action. The results revealed that, for both actions, the extent of motor resonance was related to the location of participants' fixations. The present work provides the first evidence of a relationship between gaze and motor resonance and highlights the importance of appropriate gaze behaviour for observational learning.

Cell surfaces are replete with complex, biologically important glycans responsible for multiple cellular functions including cell adhesion and cellular communication. Proper protein glycosylation is essential for normal development and often pathologies are marked by altered glycosylation. Here, data showed that the auxillary subunit, ß1, modified voltage-gated Na+ channel (Nav) gating in an isoform-specific, sialic acid dependent, and saturating manner. The regulated activity of the hundreds of glycogenes (glycosylation-associated genes) is responsible for protein glycosylation; this could result in a glycome of thousands of glycan structures. Microarray analyses indicated that glycogene expression was highly regulated throughout the heart during development. Specifically, >59% of glycogenes were significantly differentially expressed among neonatal and adult atrial and ventricular myocytes. Quantitative-PCR of individual genes confirmed the microarray analyses. Such substantial regulation of glycogene expression likely results in changes in glycan structures attached to cell surface proteins. To confirm this, myocyte glycan profiles were determined and compared among neonatal and adult atria and ventricles using mass spectrometry. The data predicted marked differences in glycan structures among myocyte types, indicating that the glycome is remodeled throughout the heart during development. To address the question of whether the remodeled glycome can impact cardiac function, action potentials and Na[subscript]v activity were measured and compared under conditions in which glycogene expression was regulated. That is, atrial and ventricular myocytes were isolated from control mice and from mice in which the polysialyltransferase, STX, was knocked out. STX is expressed in the neonatal atria, and is essentially absent in neonatal ventricle. Action potential waveforms and Nav activity measured in atrial myocytes were impacted by STX expression. No changes in ventricular action potential waveform or in Na[subscript]v activity were observed; as expected since STX is not expressed in the ventricle. The magnitude of the atrial action potential and the rate of depolarization were decreased in the absence of STX. Further, Na[subscript]v gating was shifted consistently in the depolarized direction in STX knockout atrial myocytes. Together, these data indicate that the glycome is tightly controlled and regulated in the heart, and proper glycosylation is essential for normal myocyte function.

This thesis is an investigation of the neurophysiologic mechanism, central sensitization, underlying pain and dysfunction in osteoarthritis. Central sensitization is an important mechanism in the pathophysiology of osteoarthritis but, to our knowledge, its influence on motoneurone excitability is unknown. Our primary hypothesis states that increasing central sensitization within a spinal segment will cause a greater increase in the excitability of motoneurones in subjects with osteoarthritis when compared to healthy controls. To test this hypothesis, we experimentally induced central sensitization in individuals and monitored the recruitment threshold force of the motor units in the first dorsal interosseous muscle using indwelling electromyography. Findings from this study suggest that central sensitization lowers the motor unit recruitment threshold in osteoarthritis compared to healthy individuals. Motoneurone excitability might be inhibited in healthy individuals with persistent sensitization as well. Thus, central sensitization is an important consideration in the biomechanical dysfunction seen in osteoarthritis. / Canadian Arthritis Network

The human shoulder complex relies on the sensorimotor system to maintain stability. The sensorimotor system includes sensory feedback, control of the central nervous system and motor output. Exercise is considered an important part of shoulder rehabilitation and sports training to help improve control of the sensorimotor system. However, few studies have investigated the effect of exercise on the sensorimotor system. The first study of this dissertation explored the central control of the deltoid and rotator cuff (infraspinatus). Although both the deltoid and infraspinatus contribute to shoulder abduction, the results from this study showed that the modulation of their corticospinal excitability was affected differently by elevation angle. This could be explained by the fact that they play different roles at the shoulder: the deltoid is a prime mover while the infraspinatus is a stabilizer. The second study of this dissertation investigated scapular proprioception, which has not been assessed in previous studies. The findings of this study demonstrated that joint position sense errors of the overall shoulder joint mainly came from the glenohumeral joint. Scapular proprioception may need to be tested separately in addition to overall shoulder proprioception. In the third study, the effect of the exercise on shoulder sensorimotor system was investigated by measuring shoulder kinematics, shoulder joint position sense and cortical excitability before and after a four-week exercise training program. This protocol included strengthening and neuromuscular exercises targeting rotator cuff and scapular muscles. After the training protocol, although strength increased overall, the only observed sensorimotor adaptations were a decrease in upper trapezius activation and a decrease in the corticospinal excitability of the supraspinatus. There were no changes in other key parameters. Exercises focusing on specific muscles, combined with low-intensity closed-chain exercises, were not found to improve shoulder joint position sense or scapular kinematics. Combined with the findings of the decrease in corticospinal excitability of the supraspinatus and no change in muscle activity of the rotator cuff, it appears that while the exercises increased rotator cuff strength, these gains did not transfer to an increase in muscle activation during motion. This dissertation includes previously published co-authored material.

Made available in DSpace on 2014-06-11T19:31:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-12-18Bitstream added on 2014-06-13T19:20:15Z : No. of bitstreams: 1 silvajunior_jr_dr_jabo.pdf: 913369 bytes, checksum: 3bdbada76534ca341602e017a918fbd1 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os efeitos antinociceptivos, comportamentais (atividade locomotora espontânea - ALE, altura de cabeça - AC) e sobre as variáveis fisiológicas de seis equinos tratados com tramadol, como agente analgésico preventivo, nas doses intravenosas de 2 (TT2), 3 (TT3) e 5 mg/kg (TT5), assim como da associação tramadol (3 mg/kg) e xilazina (0,5 mg/kg) (TTX) ou ainda da xilazina (0,5 mg/kg) isolada (TX) foram avaliados. Para ALE, diferenças (P<0,05) foram observadas entre os grupos TT2, TT3 e TT5, porém estas não foram significativas (P>0,05) entre esses e os grupos TTX e TX. Para a AC os grupos TTX e TX foram semelhantes sendo esses diferentes dos grupos tratados com tramadol isolado (P<0,05). Diferenças não foram observadas (P>0,05) quanto à ação antinociceptiva. No grupo TTX as variações nas frequências cardíaca e respiratória, pressão arterial sistólica e motilidade intestinal foram significativas (P<0,05). Pode-se concluir pelo exposto que, embora o tramadol isoladamente não promova alteração significativa no estado comportamental de equinos, não constitui um fármaco analgésico somático ao menos para o estímulo usado, e que a associação tramadol/xilazina, não constitui uma opção como associação, visando à sedação e à analgesia, principalmente quando for desejado incrementar, nas técnicas de anestesia, a antinocicepção somática preventiva. / Antinociceptive and behavioral effects (spontaneous locomotor activity [SLA] and head height [HH]) and effects on physiological parameters in six horses treated with tramadol as a preventive analgesic agent were assessed. Tramadol was administered at intravenous doses of 2 (TT2), 3 (TT3) and 5 mg/kg (TT5), as well as a combination of tramadol (3 mg/kg) and xylazine (0.5 mg/kg) (TTX) or xylazine alone (0.5 mg/kg) (TX). Differences in SLA (P<0.05) were seen in TT2, TT3, and TT5 groups but they were not statistically significant (P>0.05) between these groups and TTX and TX groups. TTX and TX groups showed similar HHs but there were differences of HH between TTX and TX and those groups treated with tramadol alone (P<0.05). However, no differences (P>0.05) were found regarding antinociceptive action. Significant changes (P<0.05) of heart and respiratory rates, systolic blood pressure, and intestinal motility were seen in TTX group. Although tramadol alone does not have a significant effect on horse behavior, it failed to produce analgesia and it has no somatic analgesic action to the stimulus studied. In conclusion, the combination of tramadol plus xylazine should be carefully prescribed to patients with prior cardiovascular and gastrointestinal conditions but it is not an adequate drug combination for sedation and analgesia, especially when anesthesia is intended to increase preventive somatic antinociception.

abstract: The use of a non-invasive form of energy to modulate neural structures has gained wide spread attention because of its ability to remotely control neural excitation. This study investigates the ability of focused high frequency ultrasound to modulate the excitability the peripheral nerve of an amphibian. A 5MHz ultrasound transducer is used for the study with the pulse characteristics of 57msec long train burst and duty cycle of 8% followed by an interrogative electrical stimulus varying from 30μsecs to 2msecs in pulse duration. The nerve excitability is determined by the compound action potential (CAP) amplitude evoked by a constant electrical stimulus. We observe that ultrasound's immediate effect on axons is to reduce the electrically evoked CAP amplitude and thereby suppressive in effect. However, a subsequent time delayed increased excitability was observed as reflected in the CAP amplitude of the nerve several tens of milliseconds later. This subsequent change from ultrasound induced nerve inhibition to increased excitability as a function of delay from ultrasound pulse application is unexpected and not predicted by typical nerve ion channel kinetic models. The recruitment curve of the sciatic nerve modified by ultrasound suggests the possibility of a fiber specific response where the ultrasound inhibits the faster fibers more than the slower ones. Also, changes in the shape of the CAP waveform when the nerve is under the inhibitive effect of ultrasound was observed. It is postulated that these effects can be a result of activation of stretch activation channels, mechanical sensitivity of the nerve to acoustic radiation pressure and modulation of ion channels by ultrasound. The neuromodulatory capabilities of ultrasound in tandem with electrical stimulation has a significant potential for development of neural interfaces to peripheral nerve. / Dissertation/Thesis / Masters Thesis Bioengineering 2016

The work presented in this thesis investigates whether primitive pallial brain circuits such as those found in teleost fish may also encode complex information such as spatial memory despite its circuitry being “simpler” than those found in species with much larger brains such as primates and rodents. Previous behavioral studies have already shown that most teleost fish are capable of spatially orienting themselves and remembering past food locations. Behavioral studies combined with selective brain lesions and related anatomical studies have identified a hippocampal-like region in the fish’s pallium; however, it is unknown whether the neurons located in this structure can also perform cortical-like computations as those found in the mammalian hippocampus. Consequently, this thesis will first present an anatomical characterization of the intrinsic circuitry of this hippocampal-like structure, followed by an in vitro electrophysiological characterization of its constituent neurons. Surprisingly, we have found that this hippocampal-like structure possesses many features reminiscent of the mammalian cortex, including recurrent local connectivity as well as a laminar/columnar-like organization. Furthermore, we have also identified many biophysical properties which would describe these hippocampal-like neurons as sparse coders, including a prominent after-hyperpolarizing potential and an adapting spike threshold with slow recovery. Since this particular dynamic spike threshold mechanism has not been thoroughly characterized in the mammalian hippocampus, we have further investigated the dynamic threshold in the major rodent hippocampal cell types. We have found that only a subset of excitatory neurons displayed this dynamic spike threshold on the time scale that was observed in teleost pallial cells, which allowed us to discuss its potential role in encoding spatial information in both species. Nevertheless, the fact that this teleost hippocampal homologue possesses characteristics that are both akin to the cortex and hippocampus suggest that it may perform computations that, in a mammalian brain, would require both structures and makes this ancestral structure a very interesting candidate to study the mechanism(s) underlying spatial memory.

<p>Epilepsies are the results of abnormal brain hyperactivities caused by brain injury, drug intoxication, and genetic perturbations. In the group of genetic-related epilepsies, the ion channel mutations contribute 25% of total epilepsy cases. Many studies suggest some forms of severe epilepsies can start early in patients’ lives, with epilepsy starting during infancy and childhood. With the wide adoption of genomic sequencing in children having seizures, an increasing number of <em>SCN2A</em> genetic variants have been revealed as genetic causes of epilepsy. Voltage-gated sodium channel Nav1.2, encoded by gene SCN2A, is predominantly expressed in the pyramidal excitatory neurons and supports action potential (AP) firing. One recurrent SCN2A genetic variant is L1342P, which was identified in multiple patients with epileptic encephalopathy and intractable seizures. However, the mechanism underlying L1342P-mediated seizures and the pharmacogenetics of this variant in human neurons remain unknown. To probe the potential hypothesized biophysical property changes, we used a heterologous expression system expressing the Nav1.2-L1342P. We observed prominent but quite complex gating kinetics without significant changes in window current. To understand the core phenotypes of the L1342P variant in human neurons, we took advantage of a reference human-induced pluripotent stem cell (hiPSC) line from a male donor, in which L1342P was introduced by CRISPR/Cas9-mediated genome editing. Using patch-clamping and microelectrode array (MEA) recordings, we revealed that cortical neurons derived from hiPSCs carrying heterozygous L1342P variant have significantly increased intrinsic excitability, higher sodium current density, and enhanced bursting and synchronous network firing, suggesting hyperexcitability phenotypes. Interestingly, L1342P neuronal culture displayed a degree of resistance to the anticonvulsant medication phenytoin, which recapitulated aspects of clinical observation of patients carrying the L1342P variant. In contrast, phrixotoxin-3 (PTx3), a compound showing greater specificity on Nav1.2 over other sodium channel subtypes, can potently alleviate spontaneous and chemically induced hyperexcitability of neurons carrying the L1342P variant. Our results reveal a possible pathogenic underpinning of Nav1.2-L1342P mediated epileptic seizures and demonstrate the utility of genome-edited hiPSCs as an in vitro platform to advance personalized phenotyping and drug discovery.</p>