A number of studies have shown that sensory deprivation is associated with selective decreases in GABA, GAD, and GABA receptors, in deprived areas of visual and somatosensory cortex. Those studies focused on layer 4, a recipient of direct thalamocortical sensory input. However, supragranular layers 2/3 have been recently identified as a major locus of functional plasticity in sensory deprivation and long-term potentiation. To examine whether GABAA receptors in layers 2/3 are affected by sensory deprivation, rats had mystacial vibrissae in middle row C or rows ABDE trimmed for 6 weeks beginning in early adulthood. Layers 2/3 above the deprived and adjacent whisker barrels were located in tangential sections, using patterns of radial blood vessels as fiducial marks. In deprived whisker barrel columns, [3H]muscimol binding to GABAA receptors decreased by 12.8% ± 1.2 (P &lt; 0.001) in layers 2/3 and 11.4% ± 1.2 (P<0.001) in layer 4. Altered levels of GABAA α1 subunit (Fritschy et al., 1994) were indicated by reduced optical density of immunostaining, both in deprived layers 2/3 (6.4% ± 0.7; P&lt; 0.001) and in layer 4 (3.4% ± 1.0; P &lt; 0.005). Interestingly, Nissl staining density also decreased in deprived layers 2/3 (12.7% ± 1.8 P &lt; 0.001) and in 4 (6.0 ± 0.7 (P &lt; 0.001). The percent decreases were greater in layers 2/3 than in 4 for both GABAA α1 (P &lt; 0.05) and Nissl substance (P &lt; 0.005). The present results suggest that down-regulation in GABAA receptors may underlie the physiological signs of disinhibition observed in neurons of layer 2/3 and 4 in deprived whisker barrel columns.

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第21706号 / 人健博第72号 / 新制||人健||5(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 澤本 伸克, 教授 木下 彩栄, 教授 渡邉 大 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21453号 / 医博第4420号 / 新制||医||1032(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 浅野 雅秀, 教授 林 康紀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Funktionelle bildgebende Verfahren des Gehirns messen Veränderungen des lokalen cerebralen Blutflusses bzw. der Oxygenierung, die an neuronale Aktivität gekoppelt sind, und nicht die neuronale Aktivität selbst. Diese Veränderungen breiten sich über ein größeres Areal aus als die neuronale Aktivität, das räumliche Auflösungsvermögen der bildgebenden Verfahren bleibt daher begrenzt. Es ist vorgeschlagen worden, dass der Sauerstoffverbrauch unter neuronaler Aktivierung vor dem Blutfluss ansteige. Ein initial steigender Sauerstoffverbrauch würde dann eine Deoxygenierung des Gewebes bewirken, diese bliebe exakt auf das Aeral neuronaler Aktivität beschränkt und liesse sich mit bildgebenden Verfahren darstellen, die die lokale Oxygenierung messen. Um die Hypothese der initialen Deoxygenierung zu überprüfen führten wir Messungen der intravaskulären Sauerstoffkonzentration mittels Phosphorescence Quenching im somatosensorischen Kortex von Ratten unter physiologischer Stimulation (mechanische Auslenkung der Barthaare) durch. Die Tiere wurden mit Chloralose/Urethan anästhesiert und ein kranielles Fenster über dem somatosensorischen Kortex präpariert. Der Zeitverlauf der intravaskulären Sauerstoffkonzentration unter 4s-Stimulation eines einzelnen bzw. aller Barthaare zeigte eine nach ca. 1-1,5s beginnende Hyperoxygenierung, die ihr Maximum etwa 1-1,5s nach Ende der Stimulation erreichte. Es folgte ein gering ausgeprägter post-stimulus-undershoot. Eine reproduzierbare initiale Deoxygenierung liess sich nicht nachweisen. Diese Ergebnisse sind vereinbar mit einer engen Kopplung des lokalen cerebralen Blutflusses an die neuronale Aktivität während der gesamten Stimulationsdauer. / Functional brain imaging techniques such as fMRI or PET measure regional changes in cerebral blood flow and oxygenation related to neuronal activity rather than neuronal activity itself. These changes are believed to spread over a larger area than the neuronal activity thus limiting spatial resolution of imaging techniques. It has been suggested that oxygen consumption increases before blood flow in the region of increased activity. An increased oxygen consumption would lead to an initial deoxygenation limited exactly to the aera of neuronal activity thus providing a signal detectable with techniques measuring blood oxygenation (e.g. BOLD-fMRI). To test the hypothesis of an initial deoxygenation we performed measurements of intravascular oxygen concentration in the somatosensory cortex of rats in response to a physiological stimulus (whisker deflection) using oxygen dependent phosphorescence quenching. Animals were anesthetized with chloralose/urethane and a closed cranial window was implanted over the somatosensory cortex. Timecourses of intravascular oxygen concentration during 4s single-whisker as well as whole pad deflection showed a hyperoxygenation beginning 1-1,5s second after stimulatin onset and peaking one second after the end of the stimulation. A small post-stimulus undershoot was observed. We did not reproducibly detect an initial deoxygenation. These results indicate tight coupling between neuronal activity and cerebral blood flow throughout the stimulation period.

This thesis outlines the work done on in-situ synthesis of Al2O3-ZrO2-SiCw ceramic composites and their property evaluation. The introductory chapter deals with the literature survey on ceramic matrix composites, properties desirable for structural applications and toughening mechanisms associated with these composites. The role of whisker toughening in ceramic matrix composites, the growth mechanisms involved in whisker growth and the conditions that favour or hamper the whisker growth are also discussed. The advantages and disadvantages of in-situ synthesis of composites as compared to physical mixing are also dealt with. The objective and scope of the work undertaken are outlined at the end. The second chapter describes the experimental techniques associated with carbothermal synthesis and characterisation of reaction products as well as properties of hot pressed bulk composites. The equipments used for this work are described here. The third chapter focuses on the results obtained by the carbothermal reduction of mixtures of kaolin, sillimanite and zircon taken in various proportions. The formation of the product phases with respect to variations in temperature, variations in composition and effect of catalyst is analysed with the help of XRD while their morphology is analysed using SEM. The conditions favouring the formation of tetragonal zirconia without the addition of stabilizers is also enumerated here. The fourth chapter deals with the compaction of these composite powders and the evaluation of some physical, thermal and mechanical properties. Density and porosity, coefficient of thermal expansion, modulus of rupture and fracture toughness of the composite specimens are evaluated and compared with binary and ternary composites made by other methods. Finally the thesis concludes by summarizing the work done and briefly projecting the areas for future work.

Two fundamental questions in the investigation of any sensory system are what physical signals drive its primary sensory neurons and how such signals are encoded by the successive neural levels during natural behaviour. Due to the complexity of experiments with awake, actively sensing animals, most previous studies focused on anesthetized animals, where the motor component of sensation is abolished and therefore those questions are so far largely unanswered. The aim of this thesis is to exploit recent advance in electrophysiological, behavioural and computational techniques to address those questions in the sub-cortical whisker system of the mouse. To determine the input to the whisker system, in Chapter 2 I recorded from primary whisker afferents (PWAs) of awake, head-fixed mice as they explored a pole with their whiskers, and simultaneously measured both whisker motion and forces with high-speed videography. To predict PWA firing, I used Generalised Linear Models. I found that PWA responses were poorly predicted by whisker angle, but well predicted by rotational force (moment) acting on the whiskers. This concept of “moment encoding” could account for the activity of PWAs under diverse conditions - whisking in air, active whisker-mediated touch and passive whisker deflection. The discovery that PWAs encode moment raises the question of how mice employ moment to control their tactile behaviours. In Chapter 3 I therefore measured moment at the base of the whiskers of head-fixed mice, performing a novel behavioural task, which involved whisker-based object localisation. I then tested which features of moment during whiskerobject touch could predict mouse choice. By using probabilistic classifiers, I discovered that mouse choices could be accurately predicted from moment magnitude and direction during touch, combined with a non-sensory variable - the mouse choice in the previous trial. Finally, in Chapter 4 I asked how tactile coding generalized to whisker system sub-cortical brains regions during a natural active whisker-based behaviour. I therefore combined a naturalistic whisker-guided navigation task and extracellular recording with a novel generation of high density silicon probes (O3 Neuropixel probes) and studied how touch and locomotion were encoded by the whisker first (ventral posterior nucleus, VPM) and higher order thalamic relay (posterior complex, PO) and hypothalamic regions and (zona incerta, ZI). Using multiple linear regressions, I found that neurons in the relay nucleus VPM encoded not only touch, but also locomotion signals. Similarly, neurons in the higherorder regions PO and ZI were driven by both touch and locomotion. My study showed that in the awake animal, in the central part of the whisker system, peripheral signals were preserved, but were encoded concomitantly with motor variables, such as locomotion. In summary, in this thesis I identified the mechanical variable representing the major sensory input to the whisker system. I showed that mice are able to employ it to guide behaviour and found that correlate of this signal was encoded by central neurons of the whisker system in VPM, PO and ZI, concomitantly with locomotion.

Les rongeurs utilisent leurs vibrisses pour sonder tactilement leur environnement. Tout contact induit des contraintes mécaniques lentes quasi-statiques et rapides vibratoires, qui se propagent jusqu'en base de vibrisse où des mécanorécepteurs dédiés les détectent. C'est cette étape de transduction mécanique de l'information tactile opérée par les vibrisses, avant tout codage neuronal,que nous avons étudiée.En combinant expériences biomimétiques et modélisations, nous avons cherché à isoler les contributions relatives des composantes lentes et rapides pour la détection etlocalisation d'objets, et la perception de textures. Un des enjeuxétait de comprendre ce qui d'un point de vue mécanique confère aux rongeurs leur rapidité et acuité remarquables. Pour cela, nous avons d’abord étudié la dynamique de choc vibrisse-objet, et montré que la position radiale de l’objet pouvait être encodée à la fois dans le taux de variation de la composante quasi-statique du moment en base et dans l’amplitude et la fréquence des vibrations induites. En mimant le mouvement de whisking, nous avons de plus montré qu’utiliser la composante vibratoire permet aux rongeurs une détection des contacts plus rapide et plus robuste. Nous avons ensuite étudié la perception de textures élémentaires, et montré que la variation maximale du moment en base dépendait de manière univoque de leur taille. Des expériences sur rats anesthésiés combinant suivi des vibrisses et mesures d’activité neuronale dans le cortex nous ont enfin permis de proposer un mécanisme d’encodage des textures où la topographie de la surface est modulée par les propriétés de vibrations de la vibrisse et démodulée au niveau neuronal. / Rodents use their facial whiskers to probe their environment by touch. Any contact induces both slow quasi-static and fast vibratory mechanical stresses that propagate down to the base of vibrissae where dedicated mechanoreceptors detect them. It is this phase of mechanical transduction of the tactile information operated by the whiskers, prior to any neural coding, that we have studied here. By combining biomimetic experiments and theoretical modeling, we have sought to separate the relative contributions of both slow and fast components, for the detection and localization of objects, as well as the perception of textures. One of the challenges of this work was to understand what determines from a mechanical point of view, rodents remarkable temporal and spatial precision.For this, we have first studied the shock dynamic between a whisker and an object and shown that the radial position of the object could be encoded both in the rate of change of the quasi-static component of the base torque as well as in the amplitude and frequency of the induced vibrations. In addition, by mimicking the whisking mode adopted by rodents, we have shown that using the vibratory component allows rodents to detect contacts faster and more robustly.We then studied the perception of elementary textures and showed that the maximum variation of the base torque depends univocally on their size. Experiments on anesthetized rats, combining whisker optical tracking and cortical neural activity measurements, led us to propose an encoding mechanism of texture perception where the surface topography is modulated by the vibration properties of the whiskers and demodulation occurs at a neuronal level.

In past years, legislative pressures (particularly in Japan and Europe) had forced the electronics industry to eliminate Pb from their end products and manufacturing processes. With respect to factors such as ease of converting existing tin-lead plating systems, ease of manufacture and compatibility with existing assembly methods, pure tin plating is seen by many in the industry as a potentially simple and cost effective alternative to SnPb-based systems. The problem of spontaneous tin whisker formation, a characteristic of pure tin, still needs to be addressed, as it can lead to device failure by shorting two terminals on electronic devices. This possibility gives rise to major reliability concerns. The study relates to an electronic component with pure tin deposit layer on the part for electric connection, wherein pure tin deposit layer is a fine grained tin deposit layer composed of grains with smaller size in the direction perpendicular to the deposit surface than in the direction parallel to the deposit surface. It is called irregular tin grain structure. It applies a process for plating an electronic component, so as to form a pure tin deposit layer on the part for electric connection, comprising the steps of: adjusting the composition of tin plating solution in which starter additive and brighter additive are included; moving the electronic component through the tin plating solution, so as to form a fine grained tin deposit layer on the part for electric connection. We performed a DoE by depositing different tin grain structures with variant thickness. After whisker test in high temperature/high humidity and room condition, we confirmed corrosion mechanism, intermetallic morphology, and different behaviour of tin atoms. To summarize the studies, as compared with the prior arts, irregular grain structure can validly inhibit the whisker growth.

New environmental regulations enforce the electronic industry to replace Pb-Sn solder due to Pb could contaminate our environment. Pure Sn has good material properties such as solderability, conductivity and anti-corrosion. Pure Sn is a good candidate to replace Pb-Sn solder. One of the disadvantages of pure Sn is the whisker growth phenomenon. Whisker problem has become a major concern in electronic industry due to the trend toward component miniaturization and pitch reduction. It is well understood that the root cause for tin whisker growth is the compressive stress within the tin layer. In the literature, the main stress sources are, (1) the intermetallic layer induced interface stress, (2) the difference of thermal expansion coefficient between Sn layer and substrate and (3) the mechanical residual stress from trim-form operation after tin plating. In our study, we used the electrochemical electrolysis method and Cross-section Polisher (CP) to examine the tin whisker growth mechanism. In the result, we can clearly show the Cu6Sn5 phase grow up in the tin grain boundary regions and demonstrate that the Cu6Sn5 phase formation is the main cause of the tin whisker growth. We also discuss the relationship of tin whisker growth and tin-plating process parameters that include the temperature effect; Ni underlay effect and tin-plating bath effect. For the temperature effect, the Cu6Sn5 is the major phase at 150¢XC aging. The mechanism behind its growth mechanism was grain boundary diffusion at the earlier stage and then the bulk diffusion in the later stage. The application of 150¢XC post-heat treatment could drive the bulk diffusion and form a layer type Cu6Sn5 phase to eliminate the whisker growth. For the Ni underlay effect, the Ni underlay can block the Cu atom diffusion to the tin layer and changed the tin layer stress state from compressive to tensile. Therefore, the tin whisker can be eliminated. For the tin-plating bath effect, in the sulfuric acid base and uses Triton X-100 as the surface active agent, may transform the whisker type to particular tin grain type. Thus, this tin-plating solution can restrain the tin whisker growth.

Wurtzite (W)-type ZnO condensates showed preferred orientation {10 1} when deposited on glass substrate by pulsed laser ablation on Zn target in the presence of oxygen. Such an artificial epitaxy depends on the well developed {10 1} surfaces of the condensates, which enabled {10 1}-specific coalescence to form twin and single crystal regardless of the co-deposited Zn. The W-ZnO condensates have decreasing particle size with increasing oxygen flow rate and a considerable residual stress due to the combined effects of rapid heating/cooling and thermal/lattice mismatch with Zn following parallel epitaxy or (01 )W-ZnO//(01 0)Zn; [ 2 3]W-ZnO//[0001]Zn involving {10 1} slip (Part I). In addition, wurtzite (W)-type ZnO/Zn composite deposit with preferred orientation {10 1}W-ZnO and (0001)Zn respectively on glass substrate in chapter I under Isothermal (600oC) atmospheric annealing caused self-catalyzed vapor-liquid-solid growth of rod-like W-ZnO whiskers with unusual habit. Analytical electron microscopic observations indicated that the W-ZnO whiskers extend along the zone axis of the well-developed polar surfaces {10 1} for a beneficial lower electrostatic energy and surface energy. Alternatively, the whiskers extend via {11 1}-specific growth twinning and/or coalescence twinning for a beneficial fair coincidence-site lattice at the twin boundary (Part II). Furthermore, Zn particulates overlain with wurtzite (W)-type ZnO condensates having nearly orthogonal {10 1} and {11 1} facets were found to self-catalyze unusual tapered W-ZnO whiskers upon isothermal atmospheric annealing, i.e. thermal oxidation, at 600oC. Analytical electron microscopic observations indicated that such whiskers formed tapered slabs having mosaic {10 1} and {2 1} twinned domains. The tapered whiskers can be rationalized by unconventional vapor-liquid-solid growth, i.e. {hkil}-specific coalescence twinning growth from the ZnO condensates taking advantage of a partially molten bottom source of Zn and the adsorption of atoms at the whisker tips and steps under the influence of capillarity effect (Part III). Finally, Electron irradiation of nano-size wurtzite (W)-type ZnO condensates with intimate mixture of parallel epitaxial Zn caused {10 1}W slip to form a single domain of rock salt (R)-type core and W-type shell. The two polymorphs follow (1 1)R//(0 11)W; [011]R//[ 2 3]W, i.e. chair type Peierls distortion with additional 38 degree tilting (001)R along the ( 2 0)W plane for a fair match of (10 1)W/(1 1)R, the same as one of the two paths for the back-transformation of R-ZnO into a lower crystal symmetry. The martensitic nucleation of R-type ZnO can be attributed to dynamic migration of interstitials/vacancies, lattice mismatch stress, and capillarity effect.