Convergent Recruitment of Cerebellar Purkinje Cells by Mechanistically Diverse General Anesthetics

General anesthesia produces a rapid and reversible loss of consciousness, yet the neural circuits through which chemically unrelated agents achieve this state remain largely unknown. Here, we combined Targeted Recombination in Active Populations (TRAP), Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis (CUBIC) tissue clearing, and light-sheet microscopy to generate a hemisphere-wide, single-cell atlas of neurons activated by three mechanistically distinct anesthetics in adult Fos^2A-iCreER/+; R26^Ai14/+ (TRAP2; Ai14) female mice. Automated alignment to the Atlas and unbiased effect-size analysis across 252 regions revealed a striking convergence. Vermal cerebellar lobules and their deep nuclei ranked at the top for every drug, whereas neocortical and thalamic areas showed mixed or drug-specific patterns. Within the cerebellum, the major population of tdTomato-labeled cells was the Purkinje cells, as confirmed by manual counting. Two additional subcortical hubs, the lateral paragigantocellular nucleus and external globus pallidus, were activated by all three agents, suggesting a broader cerebello-autonomic network. These results position Purkinje cells as a commonly activated population by chemically divergent anesthetics, raising the possibility that general anesthesia produces a state of loss of consciousness through the activation of Purkinje cells.