Hardwired differences: Sexually dimorphic neural connectomes in the brain-lung axis

Sexual dimorphism in lung physiology and disease is well established; yet, the underlying central circuits remain unexplored. Using retrograde trans-synaptic tracing with pseudorabies virus from the lung combined with whole-brain mapping, we uncovered fundamental sex differences in brain-lung connectivity. Male mice exhibited anterior, cognition-associated networks clustering and hemispheric lateralization, whereas female mice displayed posterior, brainstem-predominant circuits specialized for automatic respiratory control, along with more integrated and modular network architectures. These findings reveal a hardwired neural framework for sex-specific respiratory control, with implications for understanding differential susceptibility to respiratory disease between males and females.