During neocortical development, network activity undergoes a dramatic transition from largely synchronized, so-called cluster activity, to a relatively sparse pattern around the time of eye-opening in rodents. Biophysical mechanisms underlying this sparsification phenomenon remain poorly understood. Here, we present a dynamic systems modeling study of a developing neural network that provides the first mechanistic insights into sparsification. We find that the rest state of immature networks is strongly affected by the dynamics of a transient, unstable state hidden in their firing activities, allowing these networks to either be silent or generate large cluster activity. We address how, and which, specific developmental changes in neuronal and synaptic parameters drive sparsification. We also reveal how these changes refine the information processing capabilities of an in vivo developing network, mainly by showing a developmental reduction in the instability of network’s firing activity, an effective availability of inhibition-stabilized states, and an emergence of spontaneous attractors and state transition mechanisms. Furthermore, we demonstrate the key role of GABAergic transmission and depressing glutamatergic synapses in governing the spatiotemporal evolution of cluster activity. These results, by providing a strong link between experimental observations and model behavior, suggest how adult sparse coding networks may emerge developmentally.

Dans un contexte de changement climatique global et d'évolution locale de l'usage des terres, le devenir des paysages culturels des Alpes françaises, façonnés au cours des siècles par les interactions mutuelles entre sociétés et environnement, apparaît incertain. Dans le même temps, les écosystèmes qui les constituent abritent une biodiversité riche et sont à l'origine de nombreuses ressources naturelles et fonctions écologiques dont bénéficient les populations humaines. Ces ressources et fonctions sont conceptualisées sous le terme de « services écosystémiques » et font aujourd'hui l'objet d'une attention accrue dans la gestion et la protection des ressources environnementales, au même titre que la biodiversité. L'identification des facteurs liés à leur maintien, en termes écologiques, socio-culturels et politiques, est une étape nécessaire à leur gestion durable, bien qu'encore insuffisamment explorée. Mon projet de thèse visait à accroître la compréhension des interactions positives (synergies) et négatives (antagonismes) entre services écosystémiques et biodiversité via une approche multidimensionnelle du socio-écosystème des Alpes françaises. - Le Chapitre I propose une approche biophysique quantitative et spatialisée de la multifonctionnalité des écosystèmes. Suite à une étape de modélisation, les patrons spatiaux de synergie et d'antagonisme entre services et biodiversité ont été explorés statistiquement et reliés à des enjeux de gouvernance actuels à différentes échelles. Ce travail a permis d'identifier les bouquets de services écosystémiques représentatifs des différentes conditions biogéographiques, de gestion et de d'hétérogénéité du paysage représentées dans le massif. - Cette approche est complétée dans le Chapitre II par une représentation qualitative des relations d'influence entre services écosystémiques et biodiversité, ainsi que de leurs liens avec d'autres variables écologiques et sociales. Nous avons considéré explicitement les dimensions multiples englobées par le concept de service écosystémique (leurs ‘facettes') et proposons un cadre conceptuel pour en cartographier les réseaux d'influence. Ce cadre a servi de base à l'analyse d'un processus consultatif que nous avons mené auprès d'acteurs du territoire. Les analyses ont mis en lumière leur perception globale des relations d'influence importantes au sein du socio-écosystème. - Afin de mieux comprendre les régulations sociales appliquées à la gestion environnementale, nous testons dans le Chapitre III une méthodologie d'analyse de l'efficacité environnementale d'instruments de gouvernance. Notre analyse a privilégié un nombre restreint d'instruments qui encadrent actuellement les interactions entre agriculture, tourisme et biodiversité. L'utilisation d'un ensemble d'indicateurs de performance et d'adéquation avec le cadre socio-culturel et de gouvernance a souligné l'articulation complexe des instruments entre eux et a abouti à la production d'une synthèse pour les décideurs (‘policy brief'). - Le Chapitre IV explore enfin certains enjeux conceptuels et éthiques de la recherche dans le domaine des services écosystémiques. Après une réflexion générale sur les relations entre science et société, je propose une évaluation réflexive et personnelle des projets de recherche auxquels j'ai contribué. Pour conclure, je propose une vision transversale du socio-écosystème alpin mettant en lumière les enjeux majeurs identifiés par les différentes analyses. / In the context of global climate change and local land use changes, the future of the French Alps cultural landscapes, shaped through long-lasting and mutual interactions between human and their environment, appears uncertain. Simultaneously, the ecosystems constituting alpine landscapes host a rich biodiversity and provide the many natural resources and ecological functions that benefit to human societies. These resources and functions are conceptualised as “ecosystem services” and currently attract an increasing attention for the management and the conservation of environmental resources, along with biodiversity. Identifying the variables linked to their maintenance, in ecological, socio-cultural and political terms, is a necessary step of their sustainable management, and yet is still under-explored. My PhD project aimed at increasing the understanding of positive (synergies) and negative (trade-offs) interactions among ecosystem services and biodiversity through a multi-dimensional approach of the French Alps social-ecological system. - In Chapter I, I present a quantitative and spatially explicit biophysical assessment of ecosystem multifunctionality. After a modelling step, we explored spatial patterns of trade-offs and synergies among ecosystem services and biodiversity using a series of statistical analyses of increasing complexity. Results were structured to provide insights for sound environmental governance at multiple scales. We identified various bundles of ecosystem services representative of the different conditions across the French Alps massif in terms of biogeography, management and landscape heterogeneity. - This approach is complemented in Chapter II by a qualitative representation of influence relationships among ecosystem services and biodiversity that also accounts for additional ecological and social variables. We explicitly considered the multiple dimensions encompassed by the ecosystem service concept (their ‘facets') and proposed an innovative conceptual framework to represent their influence networks. This framework was applied to analyse a consultative process that we carried out with stakeholders of regional expertise. This analysis highlighted their general perception of important influence relationships in the alpine social ecological system. - In order to better understand social regulations linked to environmental governance, we test in Chapter III a methodology for assessing the environmental effectiveness of policy instruments. We concentrated on a restricted set of instruments regulating the interactions between biodiversity, agriculture and outdoor tourism. The consideration of multiple indicators assessing the performance and the fit with the socio-cultural and governance setting highlighted the complex articulation of instruments within the broader policy mix. Results were synthesised in a policy brief targeting regional decision-makers. - Chapter IV is conceived as my personal exploration of the conceptual and ethical issues linked to research on ecosystem services. Following some general thinking on the relations between environmental sciences and society, I conducted a personal reflexive assessment of the research projects I contributed to. To conclude, I propose a synthetic vision of the alpine social-ecological system and discuss the major issues revealed throughout the analyses.

Made available in DSpace on 2014-07-29T15:32:01Z (GMT). No. of bitstreams: 1 Gitair Moreira.pdf: 3199339 bytes, checksum: 54ae8591c642548d5c83145316112eef (MD5) Previous issue date: 2010-12-17 / The goal of this research was a thorough assessment of the biophysical and radiometric characteristics of the cultivated pastures in the Cerrado biome, based on both field and remote sensing data acquired in August 2009 and February 2010. The study area, located in the State of Goiás, Central Brazil, comprises an area of approximately 77.806 km², between latitudes 14º 00 S and 16º 30 S, and longitudes 48º 30 and 51º 10 W. Based on our data and results, we found a substantial difference between the two periods investigated, particularly concerning the green biomass and % green cover. While the total biomass remains mostly unchanged, the green biomass varies from 1.2 to 3.1 t/ha between August and February. Likewise, the % green cover increases as much as 65%. All these data and results, situated within the context of a larger initiative, certainly may be instrumental in promoting a more effective and sustainable pasture management in the Cerrado biome. / A presente pesquisa teve como objetivo identificar as características biofísicas e radiométricas das pastagens cultivadas do bioma Cerrado através de dados de campo e sensoriamento remoto, obtidos em agosto (período seco) e fevereiro (período chuvoso). A área de estudo localiza-se na região Centro-Oeste do Brasil, com 77.806 km², coordenadas geográficas latitude 14º 00 S a 16º 30 S e longitude 48º 30 e 51º 10 W. Com base em nossos dados e resultados há uma diferença significativa entre os dois períodos analisados, no que diz respeito aos valores de biomassa verde e porcentagem de verde, com exceção dos valores de biomassa total. Enquanto para a biomassa total os valores são 7,3 e 7,4 toneladas por hectare, em agosto e fevereiro, respectivamente, a biomassa verde varia de 1,2 para 3,1 toneladas por hectare entre agosto e fevereiro. No caso dos valores de % de verde, esta variação é ainda muito mais significativa, variando de 6 a 65%, respectivamente. A expectativa é de que estes dados, gerados e analisados no âmbito de um projeto maior de pesquisa, que envolve vários componentes temáticos e uma equipe multidisciplinar, permitam uma ocupação mais efetiva e ambientalmente sustentável das pastagens no bioma Cerrado.

Les méthodes d’amélioration des procédures de cryoconservation sont traditionnellement basées sur l’empirisme. Pour s’en démarquer, nous sommes repartis des modèles biophysiques développés pour décrire les procédures en s’appuyant sur 2 méthodes. La 1ère méthode a consisté au développement de techniques de simulation des procédures en caractérisant l’utilisation du Snomax dans l’appareil DSC. Nous avons montré que le contrôle de la température de nucléation (Tn) est possible en choisissant les conditions expérimentales (volume d’échantillon et concentration en Snomax) qui influencent les probabilités de présence de 3 sous-populations d’INA des protéines de P. syringae. La possibilité d’effectuer des simulations a pu être validée pour certaines plages de surfusion dans les solutions de cryoconservation. Ceci a permis la caractérisation des effets physiques influencés par Tn et qui interviennent au cours des procédures et d’alimenter les modèles biophysiques de cryoconservation. La 2ème méthode a consisté à la modification de la composition des solutions afin de réduire le recours au DMSO (cytotoxique) en utilisant des composés de type oligosaccharides : les COS. Après vérification de la biocompatibilité des COS avec des cellules embryonnaires, la caractérisation de l’influence thermodynamique des COS a été effectuée. Il a été montré que les COS sont des cryostabilisateurs qui se lient à une petite quantité de molécule d’eau et n’en affecte pas les propriétés physicochimiques. Les COS peuvent donc être introduits dans le milieu extracellulaire sans risque d’accélérer la déshydratation cellulaire. De plus, il a été montré qu’ils favorisent la gélification du milieu extracellulaire, laquelle est fonction de la proportion massique d’eau en solution résiduelle. Cette gélification fige une partie du système ce qui favorise sa stabilisation au passage des zones de températures à risques de recristallisation / We wished to move aside classical cryopreservation procedure improvements that are based on empiricism and to focus on existing biophysical models in order to describe procedures. We based our study on two methods. The first method consisted in developing the methods for the simulations of procedures, by characterizing the use of Snomax in a DSC device. This study highlighted that the nucleation temperature (Tn) control is possible under precise experimental conditions (sample volume and Snomax concentration) that influence the presence probability of 3 INA subpopulations of the P. syringae protein aggregates. The possibility to simulate the cryopreservation procedures has been achieved for some supercooling ranges within complex cryopreservation solutions. Consequently, it has been possible to characterize the physical effects influenced by Tn and involved within procedures. These results will participate in supplying cryopreservation biophysical models. The second method aimed to modify the composition of cryopreservative solutions in order to reduce the DMSO use (because of its cytotoxicity), using extracellular CPA components: the chitooligosaccharides COS. Subsequent to the biocompatibility verification of the COS with embryonic cells, the thermodynamic influence of the COS has been characterized. Therefore, it has been demonstrated that COS are cryostabilizers that link themselves to a small number of water molecules and does not influence its physicochemical properties. Consequently, COS can be added within the extracellular space without any risk to accelerate the cell dehydration. It has been demonstrated that COS favor the gelation of the extracellular space and that this gelation relies on the mass proportion of water in the residual solution. This gelation immobilizes a part of the system and therefore favor its stabilization when the temperature reaches the risky recrystallization range

Dans ce projet nous nous intéresserons à la création d’un nouveau modèle permettant de simuler des enregistrements extracellulaires de l’activité électrique neurale dans le système nerveux périphérique. Ce modèle fut développé pour permettre une meilleure compréhension de l’impact des différentes propriétés des interfaces sur la qualité des signaux recueillis. Ce projet fut en particulier conduit pour répondre au contexte actuel qui voit le développement de nombreuses applications dans le domaine des neuro-prothèses et autres interfaces neurales à but biomédical. Nos intentions étaient de fournir un nouvel outil permettant de mieux comprendre les particularités des interfaces existantes ou d’aider à leur amélioration et à la planification de futures innovations. Ce modèle est construit comme la synthèse de la compréhension actuelle des différents rouages biophysiques impactant les enregistrements. Sa structure peut être perçue comme l’assemblage de différents sous-systèmes interconnectés et représentant chacun une dimension du processus. Il s’avère particulièrement efficace pour l’analyse comparative des performances entre diffèrent types/géométries d’électrodes invasives. Dans ce document, nous nous efforcerons d’expliquer en détail la structure et les paramètres de notre modèle. Nous décrirons ensuite les différents tests que nous avons entrepris pour sa validation expérimentale, ainsi que les différentes voies d’applications que nous avons commencé à explorer. Nous finirons par décrire les améliorations qui nous sont apparues comme nécessaires ou possibles et par une discussion sur les ouvertures futures offerte à ce domaine de recherche. / Neural interfaces are becoming a newly dynamic and promising field especially thanks to the numerous applications they could have in the biomedical domain. A great deal of these applications requires a monitoring of targeted neural activity. Among the different technologies available for such recording practice, chronic electrodes implanted in the peripheral nervous system offer a good compromise on the resolution versus invasiveness technological constraint. A large array of electrodes has been developed in this intention but there is still only a limited comprehension of their recording principles and weakness. This makes difficult any targeted improvement of the electrodes and led this field to be mainly dominated by a trial and error empirical approach simultaneously costly in funds, animal lives and time. In particular, intrafascicular electrodes, while providing exiting results for stimulation, have often failed in recordings. These electrodes typically show interesting recording performance right after implantation but have rapid decline of their efficacy up to the points that they often become useless after a few weeks. Such performance proves problematic as they drastically limit the transfer of experimental results to human applications. The extent of our work has been the development of a theoretical framework for the study of implantable electrodes. Our goal here has been to construct a model that could be used as a platform to better understand implanted electrode and compare their performance and possible improvement. We focused our work on intrafascicular electrode for the peripheral nervous system. However, our procedure could easily be applied to other type of interface. During this project we first constructed a detailed model of the recording biophysical process happening at the peripheral nerve electrical interface. This model encompasses all the mechanism known to influence the quality and shape of neural activity recordings. We have then recreated within our model specific controlled experiments and by comparing the properties of the simulated recording with their experimental counterparts demonstrated the potency of our approach to produce bio-plausible signals. This validated our model as an in silico alternative to compare and test electrodes. We then further developed this model to also simulate some of the changes happening in the nerve post implantation. In particular, we found that the growth of the fibrotic scar could already explain a large part of the signal degradation happening in the first weeks. Then to demonstrate the adaptability of this model we used it to compare the performance of the main type of electrodes implanted nowadays peripherally. Finally, as the main weakness of our model relied in its relative complexity and the related long computing time, we started to analyze how this model could be simplified without losing the precision necessary for the intended applications. In conclusion, this project led to the creation of a model which in its current form can be used as an in silico platform to test and compare electrodes. This will facilitate the planning and development of future peripheral neural interface by proving both more economical and informative that current strategies. Conjointly, we opened the way to future improvement of our model, leading to more practicality.

During neocortical development, network activity undergoes a dramatic transition from largely synchronized, so-called cluster activity, to a relatively sparse pattern around the time of eye-opening in rodents. Biophysical mechanisms underlying this sparsification phenomenon remain poorly understood. Here, we present a dynamic systems modeling study of a developing neural network that provides the first mechanistic insights into sparsification. We find that the rest state of immature networks is strongly affected by the dynamics of a transient, unstable state hidden in their firing activities, allowing these networks to either be silent or generate large cluster activity. We address how, and which, specific developmental changes in neuronal and synaptic parameters drive sparsification. We also reveal how these changes refine the information processing capabilities of an in vivo developing network, mainly by showing a developmental reduction in the instability of network’s firing activity, an effective availability of inhibition-stabilized states, and an emergence of spontaneous attractors and state transition mechanisms. Furthermore, we demonstrate the key role of GABAergic transmission and depressing glutamatergic synapses in governing the spatiotemporal evolution of cluster activity. These results, by providing a strong link between experimental observations and model behavior, suggest how adult sparse coding networks may emerge developmentally.

<p>Peptides, specifically cell-penetrating peptides (CPP), have become wonderful research tools due to their enhanced stability, solubility, and ease of synthesis. They have been used for a wide range of biomedical applications, from insecticides to biosensors and drug-delivery scaffolds. The work presented in this dissertation characterizes the biophysical properties of two different CPPs. The first is the cationic amphiphilic polyproline helix (CAPH) peptide, P14LRR. In addition to cell penetration, this CPP has demonstrated broad spectrum antibacterial properties. Fluorescence polarization (FP) and SEC-MALS were conducted to understand the dissociation constant (KD) and oligomerization effects of P14LRR with respect to its putative molecular target in Staphylococcus aureus (S. aureus). A biotinylated derivative of this peptide was also used as a drug-delivery scaffold to transport fluorescently conjugated streptavidin into mammalian cells. A second CPP, DAN13, was also developed as a biosensor for phosphoinositide lipids, specifically PI(4,5)P2. This was effected through careful calibration using stacked supported lipid bilayers (SSLB) in combination with total internal reflection fluorescence (TIRF) microscopy. This was then used to determine the absolute densities and spatial distribution of PIP2 in live KRas mutant cells.</p>

Numerous studies showed that cochlear implant (CI) users generally prefer individualized stimulation rates in order to maximize their speech understanding. The underlying reasons for the reported variation in speech perception performance as a function of CI stimulation rate is unknown. However, multiple interacting electrophysiological processes influence the auditory nerve (AN) in response to high-rate CI stimulation. Experiments studying electrical pulse train stimulation of cat AN fibers (ANFs) have demonstrated that spike rates slowly decrease over time relative to onset stimulation and is often attributed to spike rate (spike-triggered) adaptation in addition to refractoriness. Interestingly, this decay tends to adapt more rapidly to higher stimulation rates. This suggests that subthreshold adaptation (accommodation) plays a critical role in reducing neural excitability. Using biophysical computational models of cat ANF including ion channel types such as hyperpolarization-activated cyclic nucleotide-gated (HCN) and low threshold potassium (KLT) channels, we measured the strength of adaptation in response to pulse train stimulation for a range of current amplitudes and pulse rates. We also tested these stimuli using a phenomenological computational ANF model capable of applying any combination of refractoriness, facilitation, accommodation, and/or spike rate adaptation. The simulation results show that HCN and KLT channels contribute to reducing model ANF excitability on the order of 1 to 100 ms. These channels contribute to both spike rate adaptation and accommodation. Using our phenomenological model ANF we have also shown that accommodation alone can produce a slow decay in ANF spike rates responding to ongoing stimulation. The CI users that do not benefit from relatively high stimulation rates may be due to ANF accommodation effects. It may be possible to use electrically evoked compound action potentials (ECAP) recordings to identify CI users exhibiting strong effects of accommodation, i.e., the increasing strength of adaptation as a function of increasing stimulation rate. / Dissertation / Doctor of Philosophy (PhD) / Cochlear implants (CI) attempt to restore hearing to individuals with severe to profound hearing deficits by stimulating the auditory nerve with a series of electrical pulses. Recent CI stimulation strategies have attempted to improve speech perception by stimulating at high pulse rates. However, studies have shown that speech perception performance does not necessarily improve with pulse rate increases, leading to speculation of possible causes. Certain ion channels located in auditory nerve fibers may contribute to driving the nerve to reduce its excitability in response to CI stimulation. In some cases, those channels could force nerve fibers to cease responding to stimulation, causing a breakdown in communication from the CI to the auditory nervous system. Our simulation studies of the auditory nerve containing certain types of channels showed that the effective rate of communication to the brain is reduced when stimulated at high rates due to the presence of these channels.

No description available.

Forests affect climate by absorbing CO₂ but also by altering albedo, latent heat flux, and sensible heat flux. In this study we used the Community Earth System Model to assess the biophysical effect of North American temperate forests on climate and how this effect changes with location, tree type, and forest management. We calculated the change in annual temperature and energy balance associated with afforestation with either needle leaf evergreen trees (NET) or broadleaf deciduous trees (BDT) and between forests with high and low leaf-area indices (LAI). Afforestation from crops to forests resulted in lower albedo and higher sensible heat flux but no consistent difference in latent heat flux. Forests were consistently warmer than crops at high latitudes and colder at lower latitudes. In North America, the temperature response from afforestation shifted from warming to cooling between 34° N and 40° N for ground temperature and between 21° N and 25° N for near surface air temperature. NET tended to have lower albedo, higher sensible heat flux and warmer temperatures than BDT. The effect of tree PFT was larger than the effect of afforestation in the south and in the mid-Atlantic. Increasing LAI, a proxy for increased management intensity, caused a cooling effect in both tree types, but NET responded more strongly and albedo decreased while albedo increased for BDT. Our results show that forests' location, tree type, and management intensity can have nearly equal biophysical effects on temperature. A forest will have maximum biophysical cooling effect if it is in the south, composed of broadleaf PFT, and is managed to maximize leaf area index. / Master of Science