The dynamics, interactions and phenotypes associated with the three members of the 14-3-3 family in Drosophila melanogaster

It has been proposed that the various 14-3-3 isotypes and isoforms present in all eukaryotes are largely functionally equivalent. However, this is not consistent with the conservation of multiple isoforms and isotypes, especially in vertebrates with seven 14-3-3 encoding genes and nine isotypes. The hypothesis tested in this thesis is that both isoform-specific and overlapping functions are likely mediated through tissue specific expression, colocalization and dimerization of 14-3-3 proteins occur in vivo. Drosophila melanogaster was selected because it offers a simple, but representative system to study these proteins functionally. This thesis focuses primarily on D14-3-3?, although the expression pattern and phenotypes associated with all three Drosophila 14-3-3s were determined. I first determined the expression pattern of the three different 14-3-3 isotypes (leoI, leoII and D14-3-3?) and described developmental phenotypes associated with mutations in 14-3-3 isotypes in Drosophila. I found that there is partial redundancy with respect to lethality. Both LEO and D14-3-3? appear required for normal germ-line and somatic gonadal development. However, they do not appear to be functionally equivalent with respect to this phenotype since LEO is unable to compensate for the loss of D14-3-3?. I also determined that D14-3-3? mutants have unique phenotypes including deficits in adult cross-vein formation and rapid habituation to olfactory and footshock stimuli. To further understand the unique role that D14-3-3? plays in the adult CNS, I mapped the areas in the brain involved in olfactory and footshock habituation. I found that although the mushroom bodies (MBs) are necessary to inhibit premature habituation such as that exhibited by D14-3-3? mutants, D14-3-3? expression specifically in the MBs is not sufficient to rescue premature habituation. Although the loss of either LEO or D14-3-3? appears to cause a deficit in olfactory associative learning, premature habituation is the cause of the deficit seen in D14-3-3? mutants. As leo mutants do not exhibit a premature habituation phenotype, it appears that within the MBs LEO and D14-3-3? are not functionally equivalent. Therefore, the data supports the hypothesis that 14-3-3s have functional specificity and redundancy likely to represent use of homo and heterodimers in different processes within the tissues of an organism

Sensory Urbanism Proceedings 2008

This book contains papers from the January 2008 conference, Sensory Urbanism, held by the University of Strathclyde, Glasgow, UK. Papers deal with issues surrounding the sensory perception of urban design and how to design better for all the senses. The book is illustrated throughout, and contains 26 papers from fields including architecture, urban design, environmental psychology, urban design, planning, sound design and more

29th Annual Computational Neuroscience Meeting: CNS*2020

Meeting abstracts This publication was funded by OCNS. The Supplement Editors declare that they have no competing interests. Virtual | 18-22 July 202

Modélisation de la consolidation de la mémoire dépendante de l'état d'activité du cerveau

Our brains enable us to perform complex actions and respond quickly to the external world, thanks to transitions between different brain states that reflect the activity of interconnected neuronal populations. An intriguing example is the ever-present switch of brain activity that occurs while transitioning between periods of active and quiet waking. It involves transitions from small-amplitude, high-frequency brain oscillations to large-amplitude, low-frequency oscillations, accompanied by neuronal activity switches from tonic firing to bursting. The switch between these firing modes is regulated by neuromodulators and the inherent properties of neurons. Simultaneously, our brains have the ability to learn and form memories through persistent changes in the strength of the connections between neurons. This process is known as synaptic plasticity, where neurons strengthen or weaken connections based on their respective firing activity. While it is commonly believed that putting in more effort and time leads to better performance when memorizing new information, this thesis explores the hypothesis that taking occasional breaks and allowing the brain to rest during quiet waking periods may actually be beneficial. Using a computational approach, the thesis investigates the relationship between the transitions in brain states from active to quiet waking described by the neuronal switches from tonic firing to bursting, and synaptic plasticity on memory consolidation. To investigate this research question, we constructed neurons and circuits with the ability to switch between tonic firing and bursting using a conductance-based approach. In our first contribution, we focused on identifying the key neuronal property that enables robust switches, even in the presence of neuron and circuit heterogeneity. Through computational experiments and phase plane analysis, we demonstrated the significance of a distinct timescale separation between sodium and T-type calcium channel activation by comparing various models from the existing literature. Synaptic plasticity is studied to understand learning and memory consolidation. The second contribution involves a taxonomy of synaptic plasticity rules, investigating their compatibility with switches in neuronal activity, small neuronal variabilities, and neuromodulators. The third contribution reveals the evolution of synaptic weights during the transition from tonic firing in active waking to bursting in quiet waking. Combining bursting neurons with traditional synaptic plasticity rules using soft-bounds leads to a homeostatic reset, where synaptic weights converge to a fixed point regardless of the weights acquired during tonic firing. Strong weights depress, while weak weights potentiate until reaching a set point. This homeostatic mechanism is robust to neuron and circuit heterogeneity and the choice of synaptic plasticity rules. The reset is further exploited by neuromodulator-induced changes in synaptic rules, potentially supporting the Synaptic-Tagging and Capture hypothesis, where strong weights are tagged and converge to a high reset value during bursting. While burst-induced reset may cause forgetting of previous learning, it also restores synaptic weights and facilitates the formation of new memories. To exploit this homeostatic property, an innovative burst-dependent structural plasticity rule is developed to encode previous learning through long-lasting morphological changes. The proposed mechanism explains late-stage of Long-Term Potentiation, complementing traditional synaptic plasticity rules governing early-stage of Long-Term Potentiation. Switches to bursting enable neurons to consolidate synapses by creating new proteins and promoting synapse growth, while simultaneously restoring efficacy of postsynaptic receptors for new learning. The novel plasticity rule is validated by comparing it with traditional synaptic rules in various memory tasks. The results demonstrate that switches from tonic firing to bursting and the novel structural plasticity enhance learning and memory consolidation. In conclusion, this thesis utilizes computational models of biophysical neurons to provide evidence that the switches from tonic firing to bursting, reflecting the shift from active to quiet waking, play a crucial role in enhancing memory consolidation through structural plasticity. In essence, this thesis offers computational support for the significance of taking breaks and allowing our brains to rest in order to solidify our memories. These findings serve as motivation for collaborative experiments between computational and experimental neuroscience, fostering a deeper understanding of the biological mechanisms underlying brain-state-dependent memory consolidation. Furthermore, these insights have the potential to inspire advancements in machine learning algorithms by incorporating principles of neuronal activity switches

Pheromonal modulation as a drive for behavioral plasticity in two insects: honey bees and ants

Les phéromones sont des substances chimiques relâchées dans l'environnement par un individu qui déclenchent des comportements stéréotypés et/ou des processus physiologiques chez des individus de la même espèce. Cependant, une nouvelle hypothèse suggère que les phéromones non seulement suscitent des réponses innées mais contribuent également à la plasticité comportementale en agissant en "modulateurs" de phénomènes cognitifs. Nous avons étudié l'effet modulateur des phéromones sur les réponses réflexes, la prise de décision, et l'apprentissage chez trois espèces d'insectes qui sont des modèles emblématiques en recherche fondamentale et appliquée : l'abeille Apis mellifera, et les fourmis Camponotus aethiops and Linepithema humile. Dans une première étude, nous avons trouvé qu'une phéromone appétitive diminuait la sensibilité aversive, tandis qu'une phéromone d'alarme augmentait la sensibilité aversive chez l'abeille. Chez L. humile, une phéromone de piste synthétique augmentait la sensibilité au sucre et le temps de nourrissage. Globalement, nos résultats démontrent que certaines phéromones modulent la prépondérance des stimuli aversif et appétitif selon leur valence. De cette manière, elles affecteraient la motivation à s'engager dans des réponses aversives ou appétitives, agissant ainsi comme modulateurs de la plasticité comportementale. Nous avons ensuite déterminé l'effet d'une phéromone d'alarme (l'acide formique) sur la prise de décision et les systèmes de reconnaissance dans le cadre de la discrimination de congénères chez des fourmis charpentières. Nous avons trouvé que la phéromone d'alarme améliorait la discrimination en augmentant l'agressivité envers les non congénères et en la diminuant envers les congénères en même temps. Ces résultats remettent en question le modèle établi de reconnaissance de congénères. Nous proposons donc une version révisée de ce modèle. Enfin, nous avons teste l'effet de l'acide formique sur l'apprentissage et la généralisation. L'acide formique augmentait la discrimination en conditionnement différentiel olfactif aversif. En conditionnement différentiel olfactif appétitif, l'acide formique modulait les dynamiques d'acquisition et la perception de la similarité des odeurs. Nous suggérons que les phéromones affectent la perception des odeurs conditionnées et des renforcements selon la nature des odeurs et leurs valeurs intrinsèques pour l'individu, ainsi que la valence des renforcements. Cette thèse présente les premières analyses intégrées de la modulation phéromonale chez deux taxa : les abeilles et les fourmis. Les résultats présentés nous permettent de comprendre une partie des modes d'action des phéromones et ouvrent la voie à de futures études afin de comprendre les mécanismes qui sous-tendent l'effet modulateur des phéromones.Pheromones are chemical substances released into the environment by an individual, which trigger stereotyped behaviors and/or physiological processes in individuals of the same species. Yet, a novel hypothesis has suggested that pheromones not only elicit innate responses but also contribute to behavioral plasticity by acting as "modulators" of cognitive phenomena. We studied the modulator effect of pheromones on reflex responses, decision making and learning in three insect species that are emblematic models for fundamental and applied research: the honeybee Apis mellifera, and the ants Camponotus aethiops and Linepithema humile. In the first study, we found that an appetitive pheromone decreased aversive responsiveness, while an alarm pheromone increased aversive responsiveness in honey bees. In L. humile, a synthetic trail pheromone increased sucrose responsiveness and feeding time. Overall, our results demonstrate that certain pheromones modulate the salience of aversive and appetitive stimuli according to their valence. In this way, they would affect the motivation to engage in aversive or appetitive responses, thus acting as modulators of behavioral plasticity. We then determined the effect of an alarm pheromone (formic acid) on decision making and recognition systems in the frame of nestmate discrimination in carpenter ants. We found that the alarm pheromone improved discrimination by increasing aggressiveness towards non-nestmates and decreasing aggressiveness towards nestmates at the same time. These results challenge the established model of nestmate recognition. We therefore propose a revised version of this model. Eventually, we tested the effect of formic acid on learning and generalization. Formic acid increased discrimination in aversive olfactory differential conditioning. In appetitive olfactory differential conditioning, formic acid modulated the acquisition dynamics and perceived odor similarity. We suggest that pheromones affect the perception of conditioned odors and reinforcements depending on the nature of the odorants and their intrinsic values for the individual, as well as the valence of the reinforcements. This thesis presents the first integrated analyses of pheromone modulation in two insect taxa: honey bees and ants. The presented results allow us to understand some modes of action of pheromones and pave the way for future studies to understand the underlying mechanisms of this modulator effect of pheromones

Brain Computations and Connectivity [2nd edition]

This is an open access title available under the terms of a CC BY-NC-ND 4.0 International licence. It is free to read on the Oxford Academic platform and offered as a free PDF download from OUP and selected open access locations. Brain Computations and Connectivity is about how the brain works. In order to understand this, it is essential to know what is computed by different brain systems; and how the computations are performed. The aim of this book is to elucidate what is computed in different brain systems; and to describe current biologically plausible computational approaches and models of how each of these brain systems computes. Understanding the brain in this way has enormous potential for understanding ourselves better in health and in disease. Potential applications of this understanding are to the treatment of the brain in disease; and to artificial intelligence which will benefit from knowledge of how the brain performs many of its extraordinarily impressive functions. This book is pioneering in taking this approach to brain function: to consider what is computed by many of our brain systems; and how it is computed, and updates by much new evidence including the connectivity of the human brain the earlier book: Rolls (2021) Brain Computations: What and How, Oxford University Press. Brain Computations and Connectivity will be of interest to all scientists interested in brain function and how the brain works, whether they are from neuroscience, or from medical sciences including neurology and psychiatry, or from the area of computational science including machine learning and artificial intelligence, or from areas such as theoretical physics