Coordinated Transcriptional Response to Stress-Related Disorders in Multiple Brain Regions: A Spatial and snRNA-sequencing Study in Mice

von Joy Otten
Dissertation
Datum der mündl. Prüfung:2023-11-23
Erschienen:2024-10-22
Betreuer:Prof. Dr. Dr. Torsten Klengel
Gutachter:Prof. Dr. Argyris Papantonis
Gutachter:Dr. Nico Posnien
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-10792

 

 

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Englisch

Recent work has demonstrated specific, genome-wide transcriptional changes related to fear and anxiety in rodent animal models and post-mortem human brain samples on the level of individual brain regions and even cell types. However, whether these changes are limited to a defined number of brain regions and how these changes interact on the level of transcriptional connectivity remains unknown. To address this issue, we performed spatial transcriptomics RNAseq (stRNAseq) analyses in a classical auditory threat conditioning model in C57BL/6J mice. Our results establish a molecular atlas of a relevant mouse brain section based on stRNAseq data that closely resembles histologically defined brain regions. We further provide evidence for a significant transcriptional response across all brain regions investigated, with a prominent transcriptional response in the medial and lateral habenula, and the choroid plexus. The differentially expressed genes and pathways contribute to a better understanding of the molecular correlates of threat conditioning. In addition, network analyses harnessing regional differences in gene expression between brain regions suggest changes in transcriptional connectivity between cortical and subcortical brain regions in the early phase of threat memory consolidation.
Keywords: Spatial Transcriptomics; Auditory threat conditioning; mouse model; network analyses; brain circuits; chronic social defeat stress
 
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