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Category: Project

Description: Acute stress leads to sequential activation of functional brain networks. The challenge is to get insight in whole brain activity at multiple scales, beyond the level of (networks of) nuclei. We developed a novel pre-processing and analytical pipeline to chart whole-brain immediate early genes’ expression – as proxy for cellular activity – after a single stressful foot-shock, in 4 dimensions; that is, from functional networks up to 3D single-cell resolution, and over time. The pipeline is available as R-package. Most brain areas (96%) showed increased numbers of c-fos+ cells after foot-shock, yet hypothalamic areas stood out as being most active and prompt in their activation, followed by amygdalar, prefrontal, hippocampal and finally thalamic areas. At the cellular level, c-fos+ density clearly shifted over time across subareas, as illustrated for the basolateral amygdala. Moreover, some brain areas showed increased numbers of c-fos+ cells, while others –like the dentate gyrus– dramatically increased c-fos intensity in just a subset of cells, reminiscent of engrams; importantly, this ‘strategy’ changed after foot-shock in half of the brain areas. The strength of our approach is that single-cell data were simultaneously examined across all of 90 brain areas and can be visualized in 3D in our interactive web-portal.