The misfolding of the cellular prion protein (PrPC) causes fatal neurodegenerative diseases. Yet PrPC is highly conserved in mammals, suggesting that it exerts beneficial functions preventing its evolutionary elimination. Ablation of PrPC in mice results in well-defined structural and functional alterations in the peripheral nervous system. Many additional phenotypes were ascribed to the lack of PrPC, but some of these were found to arise from genetic artifacts of the underlying mouse models. Here, we revisit the proposed physiological roles of PrPC in the central and peripheral nervous systems and highlight the need for their critical reassessment using new, rigorously controlled animal models.
During navigation, rodents continually sample the environment with their whiskers. How locomotion modulates neuronal activity in somatosensory cortex, and how it is integrated with whisker-touch remains unclear. Here, we compared neuronal activity in layer 2/3 (L2/3) and L5 of barrel cortex using calcium imaging in mice running in a tactile virtual reality. Both layers increase their activity during running and concomitant whisking, in the absence of touch. Fewer neurons are modulated by whisking alone. Whereas L5 neurons respond transiently to wall-touch during running, L2/3 neurons show sustained activity. Consistently, neurons encoding running-with-touch are more abundant in L2/3 and they encode the run-speed better during touch. Few neurons across layers were also sensitive to abrupt perturbations of tactile flow during running. In summary, locomotion significantly enhances barrel cortex activity across layers with L5 neurons mainly reporting changes in touch conditions and L2/3 neurons continually integrating tactile stimuli with running.
Study objectives Isolated REM sleep behaviour disorder (iRBD) is a parasomnia characterized by dream enactment. It represents a prodromal state of alpha-synucleinopathies, like Parkinson’s disease. In recent years, biomarkers of increased risk of phenoconversion from iRBD to overt alpha-synucleinopathies have been identified. Currently, diagnosis and monitoring rely on subjective reports and polysomnography performed in the sleep lab, which is limited in availability and cost intensive. Wearable technologies and computerized algorithms may provide comfortable and cost-efficient means to not only improve the identification of iRBD patients but also to monitor risk factors of phenoconversion. In this work, we review studies using these technologies to identify iRBD or monitor phenoconversion biomarkers. Methods A review of articles published until 31st May 2022 using the Medline database was performed. We included only papers in which subjects with RBD were part of the study population. The selected papers were divided into four sessions: actigraphy, gait analysis systems, computerized algorithms, and novel technologies. Results 25 articles were included in the review. Actigraphy, wearable accelerometers, pressure mats, smartphones, tablets, and algorithms based on polysomnography signals were used to identify RBD and monitor the phenoconversion. Rest-activity patterns, core body temperature, gait, and sleep parameters were able to identify the different stages of the disease. Conclusions These tools may complement current diagnostic systems in the future, providing objective ambulatory data obtained comfortably and inexpensively. Consequently, screening for iRBD and follow-up will be more accessible for the concerned patient cohort.
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