Spatiotemporal dynamics of odor representations in the human brain revealed by EEG decoding.

How the human brain translates olfactory inputs into diverse perceptions, from pleasurable floral smells to sickening smells of decay, is one of the fundamental questions in olfaction. To examine how different aspects of olfactory perception emerge in space and time in the human brain, we performed time-resolved multivariate pattern analysis of scalp-recorded electroencephalogram responses to 10 perceptually diverse odors and associated the resulting decoding accuracies with perception and source activities. Mean decoding accuracies of odors exceeded the chance level 100 ms after odor onset and reached maxima at 350 ms. The result suggests that the neural representations of individual odors were maximally separated at 350 ms. Perceptual representations emerged following the decoding peak: unipolar unpleasantness (neutral to unpleasant) from 300 ms, and pleasantness (neutral to pleasant) and perceptual quality (applicability to verbal descriptors such as "fruity" or "flowery") from 500 ms after odor onset, with all these perceptual representations reaching their maxima after 600 ms. A source estimation showed that the areas representing the odor information, estimated based on the decoding accuracies, were localized in and around the primary and secondary olfactory areas at 100 to 350 ms after odor onset. Odor representations then expanded into larger areas associated with emotional, semantic, and memory processing, with the activities of these later areas being significantly associated with perception. These results suggest that initial odor information coded in the olfactory areas (<350 ms) evolves into their perceptual realizations (300 to >600 ms) through computations in widely distributed cortical regions, with different perceptual aspects having different spatiotemporal dynamics.

Extracellular ATP facilitates cell extrusion from epithelial layers mediated by cell competition or apoptosis.

For the maintenance of epithelial homeostasis, various aberrant or dysfunctional cells are actively eliminated from epithelial layers. This cell extrusion process mainly falls into two modes: cell-competition-mediated extrusion and apoptotic extrusion. However, it is not clearly understood whether and how these processes are governed by common molecular mechanisms. In this study, we demonstrate that the reactive oxygen species (ROS) levels are elevated within a wide range of epithelial layers around extruding transformed or apoptotic cells. The downregulation of ROS suppresses the extrusion process. Furthermore, ATP is extracellularly secreted from extruding cells, which promotes the ROS level and cell extrusion. Moreover, the extracellular ATP and ROS pathways positively regulate the polarized movements of surrounding cells toward extruding cells in both cell-competition-mediated and apoptotic extrusion. Hence, extracellular ATP acts as an "extrude me" signal and plays a prevalent role in cell extrusion, thereby sustaining epithelial homeostasis and preventing pathological conditions or disorders.

Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial Cells.

p53 is a tumor suppressor protein, and its missense mutations are frequently found in human cancers. During the multi-step progression of cancer, p53 mutations generally accumulate at the mid or late stage, but not in the early stage, and the underlying mechanism is still unclear. In this study, using mammalian cell culture and mouse ex vivo systems, we demonstrate that when p53R273H- or p53R175H-expressing cells are surrounded by normal epithelial cells, mutant p53 cells undergo necroptosis and are basally extruded from the epithelial monolayer. When mutant p53 cells alone are present, cell death does not occur, indicating that necroptosis results from cell competition with the surrounding normal cells. Furthermore, when p53R273H mutation occurs within RasV12-transformed epithelia, cell death is strongly suppressed and most of the p53R273H-expressing cells remain intact. These results suggest that the order of oncogenic mutations in cancer development could be dictated by cell competition.