Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain.

Ketamine and isoflurane, two general anesthetics, produce unconsciousness through different neural mechanisms in mice. Ketamine activates many brain regions, especially cortical and subcortical areas involved in sensory, motor, emotional, and reward processing, with the temporal association areas acting as a strong hub, suggesting a top-down effect on consciousness by targeting higher-order cortical networks. Isoflurane primarily affects hypothalamic regions controlling neuroendocrine, autonomic, and homeostatic functions, with the locus coeruleus as a connector hub, indicating a bottom-up mechanism. Both anesthetics activate shared pathways for sensory processing, memory, cognition, reward, and autonomic control, revealing overlapping effects.

Study at a glance

Abstract

Ketamine (KET) and isoflurane (ISO) are two widely used general anesthetics, yet their distinct and shared neurophysiological mechanisms remain elusive. In this study, we conducted a comparative analysis of the effects of KET and ISO on c-Fos expression across the mouse brain, utilizing hierarchical clustering and c-Fos-based functional network analysis to evaluate the responses of individual brain regions to each anesthetic. Our findings reveal that KET activates a wide range of brain regions, notably in the cortical and subcortical nuclei involved in sensory, motor, emotional, and reward processing, with the temporal association areas (TEa) as a strong hub, suggesting a top-down mechanism affecting consciousness by primarily targeting higher order cortical networks. In contrast, ISO predominantly influences brain regions in the hypothalamus, impacting neuroendocrine control, autonomic function, and homeostasis, with the locus coeruleus (LC) as a connector hub, indicating a bottom-up mechanism in anesthetic-induced unconsciousness. KET and ISO both activate brain areas involved in sensory processing, memory and cognition, reward and motivation, as well as autonomic and homeostatic control, highlighting their shared effects on various neural pathways. In conclusion, our results highlight the distinct but overlapping effects of KET and ISO, enriching our understanding of the mechanisms underlying general anesthesia.