Project Details
Projekt
Decoding vulnerability of sensorimotor neurons to neuroinflammation
Subject Area
Molecular and Cellular Neurology and Neuropathology
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 523862973
Damage and eventual loss of neurons are a hallmark of pathology across various inflammatory diseases of the central nervous system. In multiple sclerosis, previous studies have shown that cortical lesions are a key feature of pathology, and excitatory projection neurons of the cortex have been reported to exhibit a high level of vulnerability. However, the precise molecular mechanisms that eventually lead to a loss of cortical neurons are not well understood. In this project, we will study the stepwise molecular mechanisms of neuron subtype-specific degeneration using an experimental model system that allows precise lesioning of white matter tracts. Specifically, we will induce focal lesions in the subcortical white matter and decode susceptibility of cortical neurons to that distal inflammatory lesion over time. To measure and analyze subtype-specific vulnerability of neurons, we will utilize cell type-specific and spatially resolved transcriptomics in combination with single-cell recordings and calcium imaging of cortical neurons. Further, we will perform high resolution in vivo and ultrastructural imaging to explore and decode the tissue composition across cortical layers to determine damage and vulnerability of cell-cell networks including neuronal and glial subtypes. Eventually, this project will help advance our understanding of the sequence leading to neuronal degeneration under inflammatory conditions aiming at identifying new therapeutic targets and biomarkers.
DFG Programme
Research Units
