In everyday activity we interact with objects and need to learn how to stabilize our limbs and apply appropriate forces. During learning the central nervous system adapts to the dynamics of the limb and the environment by means of formation of an accurate internal model. In the early stages of learning in the presence of novel force fields muscle cocontraction increases. Thoroughman and Shadmehr (1999) have described cocontraction as a wasted contraction. However, Franklin et al. (2003) have shown that the increase in muscle cocontraction has an important role in learning to stabilize the limb and offset the effect of the force field when the perturbing forces cannot be accurately predicted. With practice an internal model is formed which allows the central nervous system to estimate the force to counteract the force field and therefore the muscle cocontraction level declines gradually. It has been shown that the level of muscle cocontraction remains at an asymptote after learning and the amount of cocontraction depends on the amount of required impedance to provide stability (Franklin et al., 2003; Thoroughman and Shadmehr 1999). In this study, the level of muscle cocontraction in the presence of a force field of gradually increasing strength is investigated. Subjects practiced point-to-point arm movements under a training condition where the force field strength increased gradually or under a training condition where the force field was abruptly activated and remained at its maximum strength throughout training, which served as a control. At the end of the training period both groups were performing movements at maximum force field strength. Therefore, we were able to compare the level of muscle cocontraction and performance of two groups at the same high level of force field strength. The results showed that the level of muscle cocontraction in subjects who trained with the gradually increasing force field strength was lower than the group which trained with the abrupt transition to maximum force field strength both during training and subsequently when both groups performed the task at maximum force field strength. Furthermore, based on the applied force recorded during random catch trials both groups had formed an accurate internal model at the end of learning. The observed pattern of cocontraction was consistent with the learning model proposed by Franklin et al. (2008). / Dans nos activités de tous les jours, nous interagissons avec des objets, mouvements pour lesquels nous devons apprendre à stabiliser nos membres ainsi qu'à appliquer des forces adéquates. Pendant l'apprentissage de tels mouvements, le système nerveux central s'adapte à la dynamique entre les membres et l'environnement en créant un modèle interne précis. Dans les premiers stades de l'apprentissage moteur, en présence de nouvelles forces externes, une augmentation de la cocontraction musculaire est observée. Thoroughman et Shadmehr (1999) ont décrit la cocontraction musculaire comme étant une contraction gaspillée. Par contre, Franklin et al. (2003) ont démontré que l'augmentation de la cocontraction musculaire joue un rôle important dans l'apprentissage de la stabilisation des membres, tout en déviant les effets des forces externes lorsque ces forces ne peuvent être anticipées de façon précise. Avec la pratique, un modèle interne se forme ce qui permet au système nerveux central d'estimer la force nécessaire pour contrecarrer les forces externes et donc permettre une diminution graduelle de la cocontraction musculaire. Il a été démontré que le niveau de cocontraction musculaire demeure asymptotique lorsque la période d'apprentissage est terminée. À ce moment-là, le niveau de cocontraction dépend de la quantité d'impédance nécessaire pour maintenir une certaine stabilité (Franklin et al. 2003; Thoroughman and Shadmehr 1999).Dans la présente étude, le niveau de cocontraction musculaire a été examiné lors de mouvements exécutés en présence de forces externes augmentant graduellement. Les sujets ont pratiqué des mouvements du bras d'un point à un autre selon une des deux conditions d'entraînement suivantes: 1) la force externe augmentait graduellement pendant tout l'entraînement et 2) la force externe était appliquée abruptement et demeurait à son maximum pendant tout l'entraînement, servant ainsi de condition contrôle. À la fin de la période d'entraînement, les 2 groupes de sujets ont exécuté des mouvements avec des forces externes maximales. De cette façon, nous avons pu comparer le niveau de cocontraction musculaire et la performance des 2 groupes, dans une même condition de force externe élevée. Les résultats obtenus ont montré que le niveau de cocontraction musculaire chez les sujets qui se sont entraînés avec la force externe augmentant graduellement était moins élevé que chez les sujets qui se sont entraînés avec une force augmentant abruptement à un niveau de force maximale et ce, pendant l'entraînement, de même qu'au moment de l'exécution du mouvement avec une force externe maximale. De plus, selon les forces générées par les sujets, enregistrées lors d'essais-pièges, les 2 groupes de sujets ont formé un modèle interne précis à la fin de la période d'apprentissage. Le patron de cocontraction observé était en accord avec le modèle d'apprentissage moteur proposé par Franklin et al. (2008).

Neural populations in the basolateral amygdala (BLA) have been shown to be an essential substrate for associative fear memories. However, it remains unclear whether distinct associative memories are mediated by independent or overlapping populations of BLA neurons. The focus of this dissertation is to describe efforts undertaken to use reconsolidation to advance this issue. I used the fact that initiation of reconsolidation is dependant on the reactivation of a particular memory. Therefore, if two memories are stored by the same overlapping population within the BLA, then interference through blockade of reconsolidation of one should lead to impairments in both. Conversely, if the two memories are stored independently of each other within the BLA, then blockade of reconsolidation of one memory should leave the second intact. I have investigated this with two protocols that each result in two distinct fear memories. Using a single tone-shock, I investigated the relationship of auditory and contextual fear memory. My findings demonstrate a complex functional interaction between these two memories. I designed a novel 2-tone protocol with which I attempted to use the selective blockade of reconsolidation to test a model of fear memory acquisition. This attempt illuminated the need for further knowledge regarding the boundary conditions of reconsolidation. I also describe an unbiased approach to detect molecular mechanisms unique to either consolidation or reconsolidation. One candidate from this screen was validated for its role in consolidation in the BLA. The experiments described in this dissertation provide a unique view of how fear memory representations are organized in the amygdala and how manipulations of reconsolidation can be used to understand the structure of memory. / Les populations neuronales situées dans l'amygdale basolatérale (BLA) sont reconnues comme étant un substrat essentiel aux mémoires associés à la peur. Il n'est pas encore clairement établi si des souvenirs associatifs distincts sont reliés à des populations de neurones de la BLA indépendantes ou se chevauchant. Cette dissertation décritles efforts entrepris pour faire progresser nos connaissances sur cette dernière interrogation en utilisant la reconsolidation. Pour mon étude, je me suis basé sur le fait que la reconsolidation est dépendante de la réactivation d'un souvenir en particulier. Par conséquent, si deux souvenirs sont emmagasinés par la même population de neurones se chevauchant dans la BLA, alors l'interférence causée par le blocage de la reconsolidation devrait altérer les deux souvenirs. Inversement, si deux souvenirs sont emmagasinés de manière indépendante l'un de l'autre à l'intérieur de la BLA, alors le blocage de la reconsolidation d'un seul souvenir devrait laisser le second intact. J'ai examiné cette hypothèse à l'aide de deux protocoles qui ont chacun produit deux mémoires distinctes associées à la peur. En utilisant une seule association tonalité-décharge électrique, j'ai étudié la relation entre la mémoire auditive et contextuelle associée à la peur. Mes résultats ont démontrés une interaction fonctionnelle complexe entre ces deux types de souvenirs. J'ai conçu un nouveau protocole composé de deux tonalités avec lequel j'ai essayé de bloquer sélectivement la reconsolidation pour tester un modèle d'acquisition de mémoires associées à la peur. Cette expérience démontre le besoin d'en apprendre davantage sur les conditions limitant la reconsolidation. De plus, j'ai décris une approche impartiale pour détecter les mécanismes moléculaires uniques à la consolidation ou à la reconsolidation. Suite au criblage de plusieurs molécules, une molécule candidate a été reconnue pour son rôle dans la consolidation dans la BLA. Les expériences décrites dans cette dissertation amène une perspective nouvelle sur la façon dont les mémoires reliées à la peur sont organisées dans l'amygdale et démontre comment la manipulation de la reconsolidation peut être utilisée pour comprendre la structure de la mémoire.

The following work was originally undertaken in December 1951, with the hope of studying the ACTH-like activity of human blood in different physiological and pathological conditions. The acid acetone extraction of blood and the adrenal ascorbic acid depletion in hypophysectomized rats (Sayers' test) were selected as the most suitable means of approach at this time, without realizing the difficulties attendant upon the setting up of this test in the absence of extra technical assistance.

The study of the mineralocorticoid aspect of adrenal cortical activity has been accelerated in recent years by the isolation of aldosterone (1-5). That this aspect of adrenal cortical activity may be altered independently of its other aspects has been well demonstrated by the numerous published studies relating to the sodium-retaining factor recovered from the urine in various disease states (6-15).

Until recently the tumor process has been regarded as a one-step cause and effect event. The investigations during the past ten years have shown to an increasing extent the developmental character of the tumors, as well as the significance of various factors affecting the process of malignancy. Although the division of tumor process into three phases, (Induction, Critical and Progression), was suggested by Kline and Rush in 1941, it was not until 1951 that the concepts of Greene and Furth have, so to say, switched the consensus by dividing the tumors into autonomous and dependent, therefore denying the generally held view that cancer always represents an autonomous self-perpetuating entity. [...]

True Frostbite is not uncommon in civilian life (1, 17), but among acclimated travellers and natives of arctic and subarctic regions, serious cases are rare (165). The greatest incidence of frostbite has occurred among armed forces during military campaigns. Napolèon' s surgeon, Baron Larrey (101) encountered huge numbers of cold injuries in French troops during the retreat from Moscow. Lewis (108) is of the opinion that these were trench foot injuries, while Arena (5) refers to themas examples of true frostbite. During both World wars non-freezing wet cold injuries predominated.

The magnitude of the problem of ascites is not readily apparent to the clinician. A classification of conditions in which ascites occurs and a consideration of therapy occupy his thinking when confronted by a patient with the sign. Those actively engaged in investigative work on ascites have attempted to proceed further than their clinical colleagues. The vast void that exists in our knowledge becomes apparent with review of the literature. Only relative success of surgery in ameliorating chronic ascites has prompted the efforts presented within this report.

In the fall of 1946 the author was assigned to the newly formed Experimental Surgical Laboratories of McGill University with the purpose of spending one year in investigative work, as a part of a graduate training program in surgery. Experimental surgery, as a branch of surgery, was at that time in its beginnings, both at McGill University and in other centers on this continent. It is, therefore, not surprising that several serious technical difficulties have prevented the completion of the proposed research at that time. The results of the investigation recorded in this thesis have been obtained during the session 1946-1947, and completed during the current session.

The study to be reported, was undertaken to obtain further knowledge into the skin temperature changes which occur following burns and frostbite. This was stimulated by the availability of a new device for the assessment of skin temperatures. This device, the Thermoscan Model 102, was developed by the Radiation Electronics Company, a Division of Comptometer Corporation of Chicago. The Thermoscan has been used successfully by Dr. R. N. Lawson for the assessment of the temperature changes in human breasts. (94), (95). The measurement of the skin temperature has been used for many years as a means of assessing the activity of the autonomic nervous system and the peripheral circulation.

Rhythmic 24 hour variation of physiological function, in common with many other poorly understood problems, is subject to confusion in terminology. In this thesis the word "diurnal" will be used to describe events occurring during the course of a 24 hour period, not solely those occurring during the daytime. This is a concession to common usage in this field. "Nocturnal", on the other hand, will refer to events during the night; its equivalent adjective during the day will be "daytime", "matutinal", or "forenoon" and "afternoon”.