The Parasexual Cycle in Candida albicans Provides an Alternative Pathway to Meiosis for the Formation of Recombinant Strains

Candida albicans has an elaborate, yet efficient, mating system that promotes conjugation between diploid a and α strains. The product of mating is a tetraploid a/α cell that must undergo a reductional division to return to the diploid state. Despite the presence of several “meiosis-specific” genes in the C. albicans genome, a meiotic program has not been observed. Instead, tetraploid products of mating can be induced to undergo efficient, random chromosome loss, often producing strains that are diploid, or close to diploid, in ploidy. Using SNP and comparative genome hybridization arrays we have now analyzed the genotypes of products from the C. albicans parasexual cycle. We show that the parasexual cycle generates progeny strains with shuffled combinations of the eight C. albicans chromosomes. In addition, several isolates had undergone extensive genetic recombination between homologous chromosomes, including multiple gene conversion events. Progeny strains exhibited altered colony morphologies on laboratory media, demonstrating that the parasexual cycle generates phenotypic variants of C. albicans. In several fungi, including Saccharomyces cerevisiae and Schizosaccharomyces pombe, the conserved Spo11 protein is integral to meiotic recombination, where it is required for the formation of DNA double-strand breaks. We show that deletion of SPO11 prevented genetic recombination between homologous chromosomes during the C. albicans parasexual cycle. These findings suggest that at least one meiosis-specific gene has been re-programmed to mediate genetic recombination during the alternative parasexual life cycle of C. albicans. We discuss, in light of the long association of C. albicans with warm-blooded animals, the potential advantages of a parasexual cycle over a conventional sexual cycle

Cyclic and Sleep-Like Spontaneous Alternations of Brain State Under Urethane Anaesthesia

Background: Although the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM) and quiet (slow-wave or non-REM: nREM) stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state. Methodology/Principal Findings: Long-duration, multi-site forebrain field recordings were performed in urethaneanaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG) patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame (,11 minute period). Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane. Conclusions/Significance: Our results suggest that urethane promotes a condition of behavioural unconsciousness tha

The interaction of visual perception and saccadic eye movements

Primates have evolved to make high velocity, ballistic eye movements called saccades approximately three to five times per second in order to orient the high resolution part of their retina, or fovea, towards objects of interest. While saccades are generally adaptive in most situations, they also present the brain with certain challenges in order maintain a stable perception of the world. With every movement of the visual axis involving the eyes alone or through a combined eye-head gaze shift, the retina is presented with a rapidly changing view of the world. Most observers are not aware of the actual flow of incoming retinal information during a saccade, and instead perceive the world as being stable from one gaze movement to the next. How the brain accomplishes this stability has been referred to as the problem of 'trans-saccadic' perceptual stability. While this problem been pondered for more than a century by philosophers, psychologists, and neuroscientists, there is still no consensus on the precise mechanism by which visual stability is achieved. One way to approach the problem of perceptual stability is to study the way in which visual perception changes around the time of saccades. It is well known that objects briefly presented around the time of saccadic eye movements are not perceived at their veridical location, a phenomenon called perisaccadic mislocalization. Most observers make errors of two types that are predictable and systematic: a translational shift in the direction of the saccade, and compression towards the target location. This later effect, the compression of visual space towards the saccade target, is the primary phenomenon through which this thesis sought to understand the mechanisms responsible for visual stability across saccades. To this end, a series of psychophysical experiments were conducted to explore which signals may be involved in computing where an object was in space around the time of a saccade. In the fist paper, we described a biological framework in which an oculomotor signal encoding the gaze command interacts with a visual signal encoding afferent information. The outcome of this interaction was related to the perceived position of the object presented around the time of the saccade, and this formulation was able to capture both our results in addition to data from outside our laboratory. After successfully modelling the compression effect within a plausible biological framework, the next paper focused on elucidating the nature of the oculomotor signal. We accomplished this by testing observers in a variety of conditions aimed to disambiguate whether the signal was encoding the eye movement alone or the eye-head gaze shift, and found that compression was indeed linked to the eye-head gaze shift. Moreover, the experiments performed allowed us to further describe the parameters involved in modulating the compression effect. With our understanding of the compression effect and the likely biological signals involved, we then used this model to gain an enhanced understanding of how perisaccadic visual perception may be altered in patients with schizophrenia. The final paper examines the postulate that patients with schizophrenia may have an altered corollary discharge signal in the visual pathway for saccadic eye movements. With this study we were able to show that these patients do in fact exhibit qualitative differences in mislocalization compared to controls, and that these are attributable to a noisy corollary discharge that encodes the eye's position in space. This thesis comprises a systematic overview of what signals are involved in maintaining perceptual stability across saccadic eye and head movements. We have been able to investigate these signals through a combination of psychophysical studies and computational modeling. Finally, we used these paradigms to understand how these signaling mechanisms are altered in patients with schizophrenia.Au cours de l'évolution, les primates ont développé des mouvements oculaires rapides, ou les saccades. Bien que les saccades soient généralement une fonction adaptive, elles engendrent des défis important au près du système visuel qui cherche à maintenir une perception stable sur le monde. À chaque mouvement de l'axe visuel, que ce soit les yeux seuls ou la tête en combinaison avec les yeux, la rétine reçoit une nouvelle image du monde. La majorité des observateurs n'a pas conscience de ce flux important d'information rétinienne discontinue et perçoit plutôt un monde stable d'un regard à l'autre. Ce phénomène de consolidation de l'influx visuel saccadé en une perception stable et fluide du monde est intitulé le problème de la « perception stable trans-saccadique ». Le phénomène de la « perception stable trans-saccadique » peut être étudié par le biais d'une approche scientifique rigoureuse qui se penche sur la manière dont la perception visuelle évolue à travers les mouvements oculaires. Notamment, il a été démontré que les cibles présentées très brièvement lors d'un saccade sont perçu de façon erronée par rapport à leur emplacement spatial véridique, le phénomène des erreurs de localization peri-saccadique (ELPS). Ces erreurs prédictibles et systématiques sont de deux types : le premier est un simple déplacement dans la direction de la saccade ; le deuxième est sous forme de compression vers l'objet cible. Ce dernier type d'erreur, la compression du champ visuelle vers l'objet de la saccade, est le phénomène principal dont cette thèse s'est servi pour étudier les mécanismes qui engendrent la stabilité visuelle lors des saccades. Une série d'expérience psychophysique a donc été réalisée pour explorer les signaux qui entre en jeux lors du jugement spatial de la cible d'une saccade.Dans le premier chapitre, nous avons élucidé un schéma expérimental qui décrit l'interaction d'un signal oculomoteur qui encode le mouvement oculaire avec un signal visuel qui encode la position de la cible. Selon notre formulation, l'issue de cette interaction est directement reliée au positionnement perçu de la cible qui est présentée autour d'une saccade. Ce modèle a reproduit non seulement les résultats de notre laboratoire mais aussi ceux d'un collaborateur extérieur dont nous avons reçus que les données brutes. Suite à ce premier succès, lors du deuxième chapitre nous nous sommes orientés vers la nature même du signal oculomoteur. Nous avons accomplit cette tache en utilisant une variété de conditions expérimentales qui visaient à préciser si le signal visuel encodait le mouvement oculaire seule ou en conjonction avec le mouvement de la tête. Nos résultats ont clairement démontré que le phénomène de compression est en effet lié à la combinaison des mouvements des yeux et de la tête, que la compression était vers le but du regard et non l'objet de la saccade en tant que tel. Ces expériences nous ont aussi permis de décrire plus précisément les paramètres et les conditions qui affectent la compression. Armé de notre compréhension de l'effet de compression ci-haut et de ses signaux biologiques probables, lors du dernier chapitre nous avons employés notre model biologique pour comprendre davantage la manière dont la vision chez les patients atteints de la schizophrénie pourrait être altérée lors des saccades. Plus spécifiquement, nous avons étudié l'hypothèse que la décharge corollaire (DC) des voies optiques pourrait être altérée chez les patients schizophrènes. Nos études ont en effet souligné que lors des saccades, les patients schizophrènes démontrent des différences qualitatives en terme d'erreur de localisation de signal par rapport aux patients du groupe témoin. Le résultat de cette étude à démontrer que le DC dans les schizophrènes était différent que chez les contrôles, et que cette différence était suffisante pour expliquer les différences remarquées dans leur perception visuelle autour des saccades