In the pathophysiology of traumatic brain injury (TBI), the amygdala remains understudied, despite involvement in processing emotional and stressful stimuli associated with anxiety disorders, such as post-traumatic stress disorder (PTSD). Because the basolateral amygdala (BLA) integrates inputs from sensory and other limbic structures coordinating emotional learning and memory, injury-induced changes in circuitry may contribute to psychiatric sequelae of TBI. This study quantified temporal changes in dendritic complexity of BLA neurons after experimental diffuse TBI, modeled by midline fluid percussion injury. At post-injury days (PIDs) 1, 7, and 28, brain tissue from sham and brain-injured adult, male rats was processed for Golgi, glial fibrillary acidic protein (GFAP), or silver stain and analyzed to quantify BLA dendritic branch intersections, activated astrocytes, and regional neuropathology, respectively. Compared to sham, brain-injured rats at all PIDs showed enhanced dendritic branch intersections in both pyramidal and stellate BLA neuronal types, as evidenced by Sholl analysis. GFAP staining in the BLA was significantly increased at PID1 and 7 in comparison to sham. However, the BLA was relatively spared from neuropathology, demonstrated by an absence of argyrophilic accumulation over time, in contrast to other brain regions. These data suggest an early and persistent enhancement of dendritic complexity within the BLA after a single diffuse TBI. Increased dendritic complexity would alter information processing into and through the amygdala, contributing to emotional symptoms post-TBI, including PTSD.

Denna uppsats skall undersöka kopplingen mellan mental visualisering och ledarskap. Då tiderna förändras så ändras även rollen för en god ledare efter de nya förutsättningarna. Jag skall först undersöka vad som utmärker en ledarroll och vilka egenskaper som karktäriserar en god ledare. En sådan egenskap som jag tittar djupare på är mental visualisering; vart och hur är denna egenskap aktiv i en hjärna? Slutligen kommer jag försöka besavara hur eller om visualisering är en kritisk egenskap hos en god ledare. / This paper will examine the link between mental visualization and leadership. As times change so will also the role for a good leader change. I will first examine what distinguishes such a leadership and which qualities characterize a good leader. Futhermore, I will examine the possible problems  that might occur with using modern neuroscience techniques to identify the characteristics that are considered relevant for a good leadership. One such feature that I will examine closer is mental visualization. Where and how is this property active in the brain? Finally, I will try to answer how or if,  visualization is a critical characteristic of good leadership.

Networks of spiking neurons can be used not only for brain modeling but also to solve graph problems. With the use of a computationally efficient Izhikevich neuron model combined with plasticity rules, the networks possess self-organizing characteristics. Two different time-based synaptic plasticity rules are used to adjust weights among nodes in a graph resulting in solutions to graph prob- lems such as finding the shortest path and clustering.

Use-dependent long-term plasticity in synaptic connections represents the cellular substrate for learning and memory. The hippocampus is the most thoroughly investigated brain area for long-term synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD) are both well characterized in glutamatergic excitatory connections between hippocampal principal cells in vitro and in vivo. An increasing number of studies based on acute brain slice preparations report LTP and LTD in excitatory synapses onto postsynaptic hippocampal GABAergic inhibitory interneurons. However, a systematic study of activity-induced long-term plasticity in excitatory synaptic connections to inhibitory GABAergic interneurons in vivo is missing. To determine whether LTP and LTD occur in excitatory synaptic connections to the hippocampal CA1 area GABAergic interneurons types in intact brain, I have used juxtacellular recording to measure synaptically evoked short-delay postsynaptic action potential probability in identified CA1 neurons in the urethane-anaesthetized rats. Plasticity in excitatory synaptic connections to CA1 cell types was measured as a change of afferent pathway stimulation-evoked postsynaptic spike probability and delay. In the study only experiments with monosynaptic-like short-delay (range 3-12 ms) postsynaptic spikes phase-locked to afferent stimulation were used. Afferent fibres were stimulated from the CA1 area of the hippocampus at the contralateral (left) side to avoid simultaneous monosynaptic activation of GABAergic fibres and to exclude antidromic spikes in recorded CA1 cells (in right hemisphere). Plasticity in pathways was tested using theta-burst high-frequency stimulation (TBS, 100 pulses), which is one of the most common synaptic plasticity induction protocols in acute brain slice studies. I discovered that TBS elicited permanent potentiation in single shock-evoked postsynaptic spike probability with shortening or no change in evoked spike latency in various postsynaptic neuron types including three identified pyramidal cells and parvalbumin-expressing (PV+) interneurons. Most fast-spiking PV+ cells showed LTP including an axo-axonic cell and one bistratified cell, whereas two identified basket cells exhibited LTD in similar experimental conditions. In addition, I discovered diverse plasticity in non-fast spiking interneurons, reporting LTP in an ivy cell, and LTD in three incompletely identified regular-spiking CA1 interneurons. I report that the underlying brain state, defined as theta oscillation (3-6 Hz) or non-theta in local field potential, failed to explain whether LTP, LTD or no plasticity was generated in interneurons. The results show that activity-induced potentiation and depression similar to LTP and LTD also occur in excitatory synaptic pathways to various CA1 interneurons types in vivo. I propose that long-term plasticity in excitatory connections to inhibitory interneurons may be take place in learning and memory processes in the hippocampus.

In this diploma thesis has been tested potential of maternal influences on body growth at two model groups of geckos with large interspecific body size variability. The effect of egg manipulation to hatchling size was proved to be significant for hatchlings at both model species Paroedura picta and Goniurosaurus lichtenfelderi. However, in adult animals, there were no more significant body size differences caused by egg manipulation. It leads to conclusion that both species of geckos have compensatory growth and its adult size is likely to be primarily genetically determined. Key words: maternal effect, egg manipulation, body growth, allometric engeneering, Paroedura picta, Goniurosaurus lichtenfelderi

Les micro-ARNs (miRNAs) sont de petits ARNs (20-25 nt) qui ont un rôle important dans les mécanismes d'interférence ARN. Les miRNAs sont des inhibiteurs de l'expression génique qui interviennent au niveau post-traductionnel en s'hybridant à des sites spécifiques de leurs ARNm cibles. Ce mécanisme induit la dégradation de l'ARNm ou l'inhibition de sa traduction. Puisque l'hybridation partielle du miRNA est suffisante pour induire une inhibition, chaque miRNA peut avoir des centaines de cibles. Les miRNAs sont impliqués dans de nombreuses fonctions biologiques et en particulier dans processus neuronaux. Plus de la moitié des miRNAs connus sont exprimés dans le cerveau de mammifère avec une distribution spécifique du miRNA considéré. A l'échelle sub-cellulaire il y a également une distribution hétérogène des miRNAs. De plus, il a été montré récemment une implication des miRNAs dans la régulation de la traduction locale dans les neurones. En effet, des miRNAs et des protyeines impliquées dans la biogenèse et la fonction des miRNAs ont été retrouvés dans le soma, les dendrites et les axones. Il a été montré que la dérégulation des miRNAs été impliquée dans de nombreux mécanismes pathologiques. Cette thèse a pour objectif de révéler le rôle des miRNAs dans la plasticité synaptique. Nous avons étudié l'implication des miRNAs dans les mécanismes de la plasticité synaptique homéostatique et dans la plasticité dysfonctionnelle rencontrée en condition de douleur cancéreuse.Notre hypothèse était que la régulation de la traduction locale des récepteurs AMPA dans les dendrites en condition d'homéostasie synaptique implique les miRNAs. Par bio-informatique, qRT-PCR et test luciférase, nous avons identifié le miRNA miR-92a comme régulateur de la traduction de l'ARNm de GluA1. Des immunomarquages des récepteurs AMPA et des enregistrements des courants miniatures AMPA montrent que miR-92a régule spécifiquement l'incorporation synaptique de nouveau récepteurs AMPA contenant GluA1 en réponse à un blocage de l'activité synaptique. La douleur est un symptôme très fréquemment associé au cancer et constitue un challenge pour les médecins puisque aucun traitement spécifique et efficace n'existe. C'est sans doute le résultat d'un manque de connaissances des mécanismes moléculaires responsables de la douleur cancéreuse. En combinant les screening des miRNA et des ARNm, nous avons mis en évidence une voie de régulation impliquant miR-124, un miRNA enrichi dans le système nerveux. Ainsi, dans un modèle de douleur cancéreuse chez la souris, la diminution de miR-124 est associée à une augmentation de ces cibles : calpain 1, synaptopodine et tropomyosine 4. Toutes ces protéines ont précédemment été identifiées comme des molécules clef de la fonction et de la plasticité synaptique. Des experiences in vitro ont confirmé que miR-124 exercait une inhibition multiple de calpain 1, synaptopodine et tropomyosine 4. La pertinence clinique de cette découverte a été vérifiée par le screening du liquide cérébro-spinal de patients souffrant de douleur cancéreuse qui montre également une diminution de miR-124. Ce résultat suggère un fort potentiel thérapeutique du ciblage de miR-124 dans les douleurs cancéreuses. Enfin, l'injection intrathécale de miR-124 dans des souris cancéreuses a permis de normaliser l'expression de la synaptopodine et de stopper la douleur cancéreuse lors de la phase initiale de la maladie. / MicroRNAs (miRNAs) are a type of small RNA molecules (21-25nt), with a central role in RNA silencing and interference. MiRNAs function as negative regulators of gene expression at the post-transcriptional level, by binding to specific sites on their targeted mRNAs. A process results in mRNA degradation or repression of productive translation. Because partial binding to target mRNA is enough to induce silencing, each miRNA has up to hundreds of targets. miRNAs have been shown to be involved in most, if not all, fundamental biological processes. Some of the most interesting examples of miRNA activity regulation are coming from neurons. Almost 50% of all identified miRNAs are expressed in the mammalian brain. Furthermore, miRNAs appear to be differentially distributed in distinct brain regions and neuron types. Importantly, miRNAs are reported to be differentially distributed at the sub-cellular level. Recently, miRNAs have been suggested to be involved in the local translation of neuronal compartments. This has been derived from the observations reporting the presence of miRNAs and the protein complexes involved in miRNA biogenesis and function in neuronal soma, dendrites, and axons. Deregulation of miRNAs has been shown to be implicated in pathological conditions. The present thesis aimed at deciphering the role of miRNA regulation in neuronal plasticity. Here we investigated the involvement of miRNA in synaptic plasticity, specifically in homeostatic synaptic plasticity mode. In addition, we investigated the involvement of miRNAs in the maladaptive nervous system state, specifically, in bone cancer pain condition.We hypothesized that local regulation of AMPA receptor translation in dendrites upon homeostatic synaptic scaling may involve miRNAs. Using bioinformatics, qRT-PCR and luciferase reporter assays, we identified several brain-specific miRNAs including miR-92a, targeting the 3’UTR of GluA1 mRNA. Immunostaining of AMPA receptors and recordings of miniature AMPA currents in primary neurons showed that miR-92a selectively regulates the synaptic incorporation of new GluA1-containing AMPA receptors during activity blockade.Pain is a very common symptom associated with cancer and is still a challenge for clinicians due to the lack of specific and effective treatments. This reflects the crucial lack of knowledge regarding the molecular mechanisms responsible for cancer-related pain. Combining miRNA and mRNA screenings we were able to identify a regulatory pathway involving the nervous system-enriched miRNA, miR-124. Thus, miR-124 downregulation was associated with an upregulation of its predicted targets, Calpain 1, Synaptopodin and Tropomyosin 4 in a cancer-pain model in mice. All these targets have been previously identified as key proteins for the synapse function and plasticity. Clinical pertinence of this finding was assessed by the screening of cerebrospinal fluid from cancer patient suffering from pain who presented also a downregulation of miR-124, strongly suggesting miR-124 as a therapeutic target. In vitro experiments confirmed that miR-124 exerts a multi-target inhibition on Calpain 1, Synaptopodin and Tropomyosin 4. In addition, intrathecal injection of miR-124 was able to normalize the Synaptopodin expression and to alleviate the initial phase of cancer pain in mice.

Dans l'industrie nucléaire, les composants en alliages de zirconium (Zr) sont utilisés comme éléments de structure dans les assemblages combustibles. La fabrication de ces éléments, leur utilisation en Réacteur à Eau Pressurisée (REP) et leur stockage avant retraitement induisent, entre autres, des sollicitations thermo-mécaniques complexes. Ce travail, grâce à une approche expérimentale multi-échelles, propose de mieux préciser les mécanismes de déformation qui sont à considérer. Pour cela, nous avons mené, sur des échantillons prélevés sur des composants en alliage de Zr destinés à être utilisés en REP, des essais mécaniques (fluage, traction, relaxation) et, d'autre part, des caractérisations microstructurales. Des essais de fluage multiaxial ont ainsi permis de mettre en évidence une anisotropie de comportement, dont l'origine physique a été montrée au moyen d'analyses en diffraction des électrons rétrodiffusés (EBSD) et d'observations en Microscopie Electronique en Transmission (MET). Par une démarche similaire, nous avons aussi identifié la nature des mécanismes accommodant la déformation à l'échelle du grain et à celle du polycristal. Ainsi, les incompatibilités de déformation intergranulaires et les cinétiques d'écoulement viscoplastiques identifiées expérimentalement s'expliquent par l'intervention de processus de traînage d'espèces en solutions par les dislocations, ainsi que l'activation locale de vieillissement dynamique. Enfin, nous avons esquissé des pistes pour l'utilisation de ces résultats dans des modélisations numériques. / In the nuclear industry, zirconium (Zr) based alloys are used as core structural materials in Pressurized Water Reactors (PWRs). The manufacturing of those components, and their environment during or after their use in PWRs induce complex thermo-mechanical loadings. This work, through a multi-scale experimental approach, proposes to focus on the deformation mechanisms that occur during those loadings. Using samples taken from Zr alloy components, we carried out different mechanicals tests (creep tests, tensile tests, relaxation tests) and microstructural characterizations. Results of multiaxial creep tests were correlated to Transmission Electron Microscope (TEM) observations and Electron BackScattered Diffraction (EBSD) analyses. Therefore, the macroscopic creep anisotropy was related to the physical mechanisms observed at the dislocation scale and during mesoscopic measurements. Our conclusions also show that the viscoplastic properties obtained experimentally match a control of dislocation mobility by solute species dragging processes. Further, the intergranular strain incompatibilities that we observed could be explained by local activations of dynamic strain ageing mechanisms. Finally, we used our results to suggest improvements on physically-based modelling techniques.

La création photographique fonde et se fonde sur des conditions et des conduites d’émergence et de développement, que l’image ne saisit pas toujours, ou dont elle choisit de se dessaisir. Notre travail propose d’explorer les modalités et les enjeux du dévoilement des instances poïétiques dans l’image photographique. Par le biais d’une mise en tension des termes propres à l’atelier et au laboratoire photographique, nous situons ces deux espaces d’actions au coeur d’un territoire plastique ouvert aux interactions et aux circulations des éléments en jeu dans les divers processus et procédures suivis ou tracés. Notre pratique plastique engage le procédé photographique vers des dispositifs archaïques et vers de nouvelles fonctionnalités qui privilégient les voies de l’élaboration plastique, de l’expérience et de la réflexivité. Les motifs réflexifs mettent en question les fictions en construction et en éclairent en même temps les fondations ou les fondements. Le processus ne tend plus vers la restitution d’un résultat visé, mais vers des visions singulières qui retracent les expériences menées et vécues dans le laboratoire-atelier. Les ressorts poïétiques de la dissémination, de la sédimentation et de la fiction participent d’un chantier d’instauration plastique et photographique qu’ils donnent à voir et qu’ils redéfinissent sans cesse. / Creative photography implies and is based on conditions and emerging and developing behaviours, that the image does not always seize or chooses to impart. Our work aims to explore the modalities and goals of poietic disclosure inside the image. Through the opposition of terms specific to the studio and photographic laboratory, we set both spaces at the heart of an artistic territory, open to interactions and flows of the elements involved in the various processes and procedures followed or traced. Our fin art practice engages the photographic process to archaic devices and new functionalities that focus on developing artistic work, experience, and reflexivity. The reflexive patterns disturb fictions in construction, and point to their foundation. The process does not tend anymore towards the restoration of a preexistent outcome, but rather to singularities reflecting the experiments made or experienced in the photographic studio. Poietic methods of dissemination, sedimentation and fiction are part of en establishing fine art and photographic site, they present and remodel.

Doctor of Philosophy / Division of Biology / Theodore Morgan / Temperature is a critical environmental parameter and thermal variation has significant effects on local adaptation and species distributions in nature. This is especially true for organisms that are isothermal with their environment. Variation in temperature imposes stress and directly influences physiology, behavior, and fitness. Thus, to thrive across a range of thermal environments populations must contain sufficient genetic variation, the capacity to respond plastically, or some combination of both genetic and plastic responses. In this work I first quantified patterns of phenotypic and genetic variation in nature and then dissected the genetic basis of variation in thermal traits. In the first aim I used natural populations of Drosophila melanogaster collected from a latitudinal transect in Argentina to investigate variation in heat stress resistance and cold plasticity within and among populations. I found heat stress resistance was highly variable within populations, but was strongly associated with the monthly maximum average temperature of each site. For cold plasticity I was able to demonstrate significant variation in plasticity within and among populations, however the among population variation was best explained by the altitude of each site. I hypothesized that this was caused by a difference in temperature fluctuations at high altitude sites relative to low altitude sites. To evaluate this hypothesis I paired our study with existing laboratory data that demonstrated significant fitness differences between high and low plasticity (and altitude) sites when these populations were reared in variable thermal environments. Thus, cold plasticity is an adaptive response to environmental variation. The final project focused on understanding the genetic basis of thermal variation. I fine-mapped a single co-localized heat and cold tolerance QTL via deficiency and mutant complementation mapping to identify four novel thermal candidate genes. There was no overlap of the deficiencies or genes associated with cold or heat stress resistance. Sequence analysis of each gene identified the polymorphisms that differentiate the lines. To test for independent associations between these polymorphisms and variation in nature the Drosophila Genome Reference Panel was used to confirm associations between allelic variation and cold tolerance in nature.

Master of Science / Department of Biology / Theodore J. Morgan / The organismal response to temperature represents one of the most ubiquitous processes that occur in the natural world, and this response is critical for survival in most habitats. Increased attention should be focused on how organisms cope with temperature extremes, either through adaptation, plasticity, or a combination of both, as climate models predict increased variations in temperature accompanied by novel thermal extremes. Drosophila melanogaster is an excellent resource for answering questions pertaining to how organisms persist in environmental extremes because they originated in central tropical Africa and have since colonized nearly the entire globe, exposing them to many novel thermal stressors. In this work I elucidated regions of the genome contributing to phenotypic variation in cold tolerance and thermal plasticity. A quantitative trait locus (QTL) approach was used, which involved phenotyping roughly 400 recombinant inbred lines (RILs) of D. melanogaster from the Drosophila Synthetic Population Resource (DSPR). The DSPR captures genetic variation from around the globe, allowing for precision mapping of cold tolerance and thermal plasticity QTL, while simultaneously determining the frequency of the QTL alleles. Upon development at both 18°C and 25°C, RILS were measured for a common cold tolerance metric, chill-coma recovery time (CCR), and a plasticity value was derived as the change in CCR between environments. Analysis of variance revealed significant effects of sex, line (RIL), treatment (temperature), and line by treatment interaction (GxE). Mapped QTL for chill-coma recovery time at 18°C and 25°C spanned the same regions as several studies previously reported, validating the automated phenotyping method used and the mapping power of the DSPR. QTL between CCR at 18°C and 25°C overlapped significantly, and QTL for thermal plasticity shared the similar regions as QTL for CCR, but also exhibited two non-overlapping QTL on the left arm of the third chromosome. This study demonstrated the tremendous amount of variation present in cold tolerance phenotypes and identified candidate regions of the genome that contribute to thermal plasticity and require further investigation.