Biology subjects

Tevosian, M.

Publications and source records attributed to Tevosian, M..

3 recordsLinked to original sources

bioRxiv2024

ClearFinder: a Python GUI for annotating cells in cleared mouse brain

BackgroundTissue clearing combined with light-sheet microscopy is gaining popularity among neuroscientists interested in unbiased assessment of their samples in 3D volume. However, the analysis of such data remains a challenge. ClearMap and CellFinder are tools for analyzing neuronal activity maps in an intact volume of cleared mouse brains. However, these tools lack a user interface, restricting accessibility primarily to scientists proficient in advanced Python programming. The application presented here aims to bridge this gap and make data analysis accessible to a wider scientific community. ResultsWe developed an easy-to-adopt graphical user interface for cell quantification and group analysis of whole-cleared adult mouse brains. Fundamental statistical analysis, such as PCA and box plots, and additional visualization features allow for quick data evaluation and quality checks. Furthermore, we report significant differences in total cell counts between CellFinder and ClearMap when cross-analyzing the same samples, underscoring the need for optimizing reproducibility within the field. ConclusionsOur easily accessible tool allows more researchers to implement the methodology, troubleshoot arising issues, and develop quality checks, benchmarking, and standardized analysis pipelines for cell detection and region annotation in whole volumes of cleared brains.

bioinformatics↗

bioRxiv2023

Freezing responses during prolonged threat memory retrieval reflect trait-like anxiety endophenotypes in female and male inbred mice

Trait anxiety is a major risk factor for stress-induced and anxiety disorders in humans. However, animal models accounting for the inter-individual variability in stress vulnerability are largely lacking. Moreover, the pervasive bias of using mostly male animals in preclinical studies poorly reflects the increased prevalence of psychiatric disorders in women. Using the threat imminence continuum theory, we designed and validated an auditory aversive conditioning-based pipeline in both female and male mice. We operationalized trait anxiety by harnessing the naturally occurring variability of defensive freezing responses combined with a model-based clustering strategy. While sustained freezing during prolonged retrieval sessions was identified as an anxiety-endophenotype biomarker in both sexes, females were consistently associated with an increased freezing response RNA-sequencing of CeA, BLA, ACC and BNST revealed massive differences in phasic and sustained responders transcriptomes, correlating with transcriptomic signatures of psychiatric disorders, particularly PTSD. Moreover, we detected significant alterations in the excitation/inhibition balance of principal neurons in the lateral amygdala. These findings provide compelling evidence that trait anxiety in inbred mice can be leveraged to develop translationally relevant preclinical models to investigate mechanisms of stress susceptibility in a sex-specific manner. We like to think we have constrained an organism to the task we have set. In practice, our paradigms are constrained by the way the organisms respond McNaughton & Corr, 2004

neuroscience↗

bioRxiv2023

Repair oligodendrocytes demyelinating and disintegrating damaged axons after injury

After a spinal cord injury, axons fail to regrow, which results in permanent loss of function1. This is in contrast with peripheral axons that can regrow efficiently after injury2. These differences are partly due to the different plasticity of myelinating cells, Schwann cells and oligodendrocytes, in these two systems3. The molecular mechanisms underlying this different plasticity remain however poorly understood. Here, we show that the phosphatase Dusp64 is a master inhibitor of oligodendrocyte plasticity after spinal cord injury. Dusp6 is rapidly downregulated in Schwann cells and upregulated in oligodendrocytes after axon injury. Simultaneously, the MAP kinases ERK1/2 are activated and the transcription factor c-Jun is upregulated in Schwann cells5,6, but not in oligodendrocytes. Ablation or inactivation of Dusp6 induces rapid ERK1/2 phosphorylation, c-Jun upregulation and filopodia formation in oligodendrocytes, leading to mechanically-induced, fast disintegration of distal ends of injured axons, myelin clearance and axonal regrowth. Together, our findings provide understanding of the mechanisms underlying the different plasticity of Schwann cells and oligodendrocytes after injury and a method to convert mature oligodendrocytes exhibiting inhibitory cues for axonal regrowth into repair oligodendrocytes reminiscent of repair Schwann cells. We show that repair oligodendrocytes successfully increase the compatibility of the spinal cord environment with axonal regrowth after injury, suggesting a potential use of repair oligodendrocytes as future therapeutic approach to treat spinal cord injuries.

neuroscience↗