High resolution, high capacity, spatial specificity in perceptual learning.

Research of perceptual learning has received significant interest due to findings that training on perceptual tasks can yield learning effects that are specific to the stimulus features of that task. However, recent studies have demonstrated that while training a single stimulus at a single location can yield a high-degree of stimulus specificity, training multiple features, or at multiple locations can reveal a broad transfer of learning to untrained features or stimulus locations. We devised a high resolution, high capacity, perceptual learning procedure with the goal of testing whether spatial specificity can be found in cases where observers are highly trained to discriminate stimuli in many different locations in the visual field. We found a surprising degree of location specific learning, where performance was significantly better when target stimuli were presented at 1 of the 24 trained locations compared to when they were placed in 1 of the 12 untrained locations. This result is particularly impressive given that untrained locations were within a couple degrees of visual angle of those that were trained. Given the large number of trained locations, the fact that the trained and untrained locations were interspersed, and the high-degree of spatial precision of the learning, we suggest that these results are difficult to account for using attention or decision strategies and instead suggest that learning may have taken place for each location separately in retinotopically organized visual cortex

Phthiocerol Dimycocerosates of M. tuberculosis Participate in Macrophage Invasion by Inducing Changes in the Organization of Plasma Membrane Lipids

Phthiocerol dimycocerosates (DIM) are major virulence factors of Mycobacterium tuberculosis (Mtb), in particular during the early step of infection when bacilli encounter their host macrophages. However, their cellular and molecular mechanisms of action remain unknown. Using Mtb mutants deleted for genes involved in DIM biosynthesis, we demonstrated that DIM participate both in the receptor-dependent phagocytosis of Mtb and the prevention of phagosomal acidification. The effects of DIM required a state of the membrane fluidity as demonstrated by experiments conducted with cholesterol-depleting drugs that abolished the differences in phagocytosis efficiency and phagosome acidification observed between wild-type and mutant strains. The insertion of a new cholesterol-pyrene probe in living cells demonstrated that the polarity of the membrane hydrophobic core changed upon contact with Mtb whereas the lateral diffusion of cholesterol was unaffected. This effect was dependent on DIM and was consistent with the effect observed following DIM insertion in model membrane. Therefore, we propose that DIM control the invasion of macrophages by Mtb by targeting lipid organisation in the host membrane, thereby modifying its biophysical properties. The DIM-induced changes in lipid ordering favour the efficiency of receptor-mediated phagocytosis of Mtb and contribute to the control of phagosomal pH driving bacilli in a protective niche

Mycobacterium leprae Phenolglycolipid-1 Expressed by Engineered M. bovis BCG Modulates Early Interaction with Human Phagocytes

The species-specific phenolic glycolipid 1 (PGL-1) is suspected to play a critical role in the pathogenesis of leprosy, a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. Based on studies using the purified compound, PGL-1 was proposed to mediate the tropism of M. leprae for the nervous system and to modulate host immune responses. However, deciphering the biological function of this glycolipid has been hampered by the inability to grow M. leprae in vitro and to genetically engineer this bacterium. Here, we identified the M. leprae genes required for the biosynthesis of the species-specific saccharidic domain of PGL-1 and reprogrammed seven enzymatic steps in M. bovis BCG to make it synthesize and display PGL-1 in the context of an M. leprae-like cell envelope. This recombinant strain provides us with a unique tool to address the key questions of the contribution of PGL-1 in the infection process and to study the underlying molecular mechanisms. We found that PGL-1 production endowed recombinant BCG with an increased capacity to exploit complement receptor 3 (CR3) for efficient invasion of human macrophages and evasion of inflammatory responses. PGL-1 production also promoted bacterial uptake by human dendritic cells and dampened their infection-induced maturation. Our results therefore suggest that M. leprae produces PGL-1 for immune-silent invasion of host phagocytic cells

High resolution, high capacity, spatial specificity in perceptual learning.

Research of perceptual learning has received significant interest due to findings that training on perceptual tasks can yield learning effects that are specific to the stimulus features of that task. However, recent studies have demonstrated that while training a single stimulus at a single location can yield a high-degree of stimulus specificity, training multiple features, or at multiple locations can reveal a broad transfer of learning to untrained features or stimulus locations. We devised a high resolution, high capacity, perceptual learning procedure with the goal of testing whether spatial specificity can be found in cases where observers are highly trained to discriminate stimuli in many different locations in the visual field. We found a surprising degree of location specific learning, where performance was significantly better when target stimuli were presented at 1 of the 24 trained locations compared to when they were placed in 1 of the 12 untrained locations. This result is particularly impressive given that untrained locations were within a couple degrees of visual angle of those that were trained. Given the large number of trained locations, the fact that the trained and untrained locations were interspersed, and the high-degree of spatial precision of the learning, we suggest that these results are difficult to account for using attention or decision strategies and instead suggest that learning may have taken place for each location separately in retinotopically organized visual cortex

Dissociating electrophysiological correlates of contextual and perceptual learning in a visual search task.

Perceptual learning and contextual learning are two types of implicit visual learning that can co-occur in the same tasks. For example, to find an animal in the woods, you need to know where to look in the environment (contextual learning) and you must be able to discriminate its features (perceptual learning). However, contextual and perceptual learning are typically studied using distinct experimental paradigms, and little is known regarding their comparative neural mechanisms. In this study, we investigated contextual and perceptual learning in 12 healthy adult humans as they performed the same visual search task, and we examined psychophysical and electrophysiological (event-related potentials) measures of learning. Participants were trained to look for a visual stimulus, a small line with a specific orientation, presented among distractors. We found better performance for the trained target orientation as compared to an untrained control orientation, reflecting specificity of perceptual learning for the orientation of trained elements. This orientation specificity effect was associated with changes in the C1 component. We also found better performance for repeated spatial configurations as compared to novel ones, reflecting contextual learning. This context-specific effect was associated with the N2pc component. Taken together, these results suggest that contextual and perceptual learning are distinct visual learning phenomena that have different behavioral and electrophysiological characteristics

Alpha-band EEG activity in perceptual learning

In studies of perceptual learning (PL), subjects are typically highly trained across many sessions to achieve perceptual benefits on the stimuli in those tasks. There is currently significant debate regarding what sources of brain plasticity underlie these PL-based learning improvements. Here we investigate the hypothesis that PL, among other mechanisms, leads to task automaticity, especially in the presence of the trained stimuli. To investigate this hypothesis, we trained participants for eight sessions to find an oriented target in a field of near-oriented distractors and examined alpha-band activity, which modulates with attention to visual stimuli, as a possible measure of automaticity. Alpha-band activity was acquired via electroencephalogram (EEG), before and after training, as participants performed the task with trained and untrained stimuli. Results show that participants underwent significant learning in this task (as assessed by threshold, accuracy, and reaction time improvements) and that alpha power increased during the pre-stimulus period and then underwent greater desynchronization at the time of stimulus presentation following training. However, these changes in alpha-band activity were not specific to the trained stimuli, with similar patterns of posttraining alpha power for trained and untrained stimuli. These data are consistent with the view that participants were more efficient at focusing resources at the time of stimulus presentation and are consistent with a greater automaticity of task performance. These findings have implications for PL, as transfer effects from trained to untrained stimuli may partially depend on differential effort of the individual at the time of stimulus processing