Brain-wide mapping of acute hypoxia-induced neuronal activation in mice: A c-Fos immunofluorescence study

Abstract

Acute hypobaric hypoxic exposure, defined as rapid ascent to high altitude with brief sojourn, triggers profound physiological adaptations while increasing risks of acute mountain sickness (e.g., gastrointestinal distress, pulmonary/cerebral edema). Beyond these somatic manifestations, cognitive deficits frequently emerge under hypoxic stress, yet the neural substrates mediating these impairments remain poorly mapped. To systematically characterize hypoxia-induced brain activation patterns, we conducted whole-brain mapping of neuronal activity changes in mice exposed to acute hypobaric hypoxia versus normoxic controls using c-Fos immunofluorescence, a robust marker of neuronal activation. Our functional analysis focused on key brain regions governing: cardiorespiratory homeostasis, attention, memory, emotional processing, motivation and reward. Quantitative c-Fos mapping revealed increased neural activity in several brainstem nuclei and repressed neural activity in higher-order forebrain after exposure to 24 h-6000 m hypobaric hypoxia. These datas establish the first brain-wide map of hypoxia-responsive neural networks, providing mechanistic insights into physiological adaptation and cognitive vulnerability after acute hypobaric hypoxic exposure.