Biology subjects

Medina, J. F.

Publications and source records attributed to Medina, J. F..

3 recordsLinked to original sources

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↗

bioRxiv2020

Immediate and long-term effects of transcranial direct-current stimulation in the mouse primary somatosensory cortex

Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation technique consisting in the application of weak electric currents on the scalp. Although previous studies have demonstrated the clinical value of tDCS for modulating sensory, motor, and cognitive functions, there are still huge gaps in the knowledge of the underlying physiological mechanisms. To define the immediate impact as well as the after-effects of tDCS on sensory processing, we first performed electrophysiological recordings in primary somatosensory cortex (S1) of alert mice during and after administration of S1-tDCS, and followed up with immunohistochemical analysis of the stimulated brain regions. During the application of cathodal and anodal transcranial currents we observed polarity-specific bidirectional changes in the N1 component of the sensory-evoked potentials (SEPs) and associated gamma oscillations. Regarding the long-term effects observed after 20 min of tDCS, cathodal stimulation produced significant after-effects including a decreased SEP amplitude for up to 30 min, a power reduction in the 20-80 Hz range and a decrease in gamma event related synchronization (ERS). In contrast, no significant long-term changes in SEP amplitude or power analysis were observed after anodal stimulation except for a significant increase in gamma ERS after tDCS cessation. The polarity-specific differences of these long-term effects were corroborated by immunohistochemical analysis, which revealed an unbalance of GAD 65-67 immunoreactivity between the stimulated vs. non-stimulated S1 region only after cathodal tDCS. These results highlight the differences between immediate and long-term effects of tDCS, as well as the asymmetric long-term changes induced by anodal and cathodal stimulation. Significance StatementHere we provide a first glimpse at the immediate and long-term impact of tDCS on neural processing in alert animals. The obtained results highlight the complexity of tDCS-associated effects, which include both bidirectional as well as asymmetrical modulation depending on the polarity of the stimulation. This asymmetry suggests the implication of different mechanisms underlying the long-term effects induced by anodal and cathodal transcranial currents. Identifying and defining these effects and its associated mechanisms is crucial to help design effective protocols for clinical applications.

neuroscience↗