Ohmae, S. | bioRxiv Science

bioRxiv2021

P-sort: an open-source software for cerebellar neurophysiology

Analysis of electrophysiological data from Purkinje cells (P-cells) of the cerebellum presents challenges for spike detection. Complex spikes have waveforms that vary significantly from one event to the next, raising the problem of misidentification. Even when complex spikes are detected correctly, the simple spikes may belong to a different P-cell, raising the danger of misattribution. Here, we analyzed data from over 300 P-cells in marmosets, macaques, and mice, using an open-source, semi-automated software called P-sort that addresses the spike identification and attribution problems. Like other sorting software, P-sort relies on nonlinear dimensionality reduction to cluster spikes. However, it also uses the statistical relationship between simple and complex spikes to merge seemingly disparate clusters, or split a single cluster. In comparison with expert manual curation, occasionally P-sort identified significantly more complex spikes, as well as prevented misattribution of clusters. Three existing automatic sorters performed less well, particularly for identification of complex spikes. To improve development of analysis tools for the cerebellum, we provide labeled data for 313 recording sessions, as well as statistical characteristics of waveforms and firing patterns.

neuroscience↗

bioRxiv2020

Deleting Mecp2 from the entire cerebellum rather than its neuronal subtypes causes a delay in motor learning in mice

Rett syndrome is a devastating childhood neurological disorder caused by mutations in MECP2. Of the many symptoms, motor deterioration is a significant problem for patients. In mice, deleting Mecp2 from the cortex or basal ganglia causes motor dysfunction, hypoactivity, and tremor, which are abnormalities observed in patients. However, little is known about the consequences of deleting Mecp2 from the cerebellum, a brain region critical for motor function. Here we show that deleting Mecp2 from the entire cerebellum, but not from individual cerebellar cell types, causes a delay in motor learning that is overcome by additional training. We also observed irregular firing rates of Purkinje cells and transcriptional misregulation within the cerebellum of knockout mice. These findings demonstrate that the motor deficits present in Rett syndrome arise, in part, from cerebellar dysfunction. For Rett syndrome as well as other neurodevelopmental disorders, our results highlight the importance of understanding which brain regions contribute to disease phenotypes.

neuroscience↗