Pseudorabies virus tracing maps multisynaptic uterus-brain circuit, revealing olfactory modulation of uterine activity.

The uterus is critical for maintaining reproductive health and fertility, with its function precisely regulated by the central nervous system (CNS). While a general brain-uterus connection is known, the specific multisynaptic neural pathways and how external stimuli, such as olfactory cues, modulate uterine activity remain poorly understood. Current understanding lacks detailed circuit maps, limiting insights into conditions like infertility or reproductive disorders. This study aimed to delineate these complex neural connections and explore the role of olfaction.

Researchers employed multimodal neural tracing and c-Fos staining in mice to investigate uterus-CNS pathways. PRV-CAG-EGFP was injected into the uterine myometrium to trace multisynaptic connections. Subsequent anatomical tracing identified connections between olfactory/accessory olfactory bulbs and specific brain regions. An odorant screening experiment used butyric acid (BA) to identify activated brain areas, with nasal mucosal injury serving as a control to confirm olfactory pathway dependence. Finally, co-labeling experiments combined PRV tracing with c-Fos staining to identify uterus-connected neurons activated by BA, including those co-expressing oxytocin.