Terrestrial quadrupeds stabilize dorsal-side-up body orientation (the vertical orientation of its dorso-ventral axis) through the postural control system, with supraspinal inputs, including those from the reticular formation, playing a central role. The contribution of specific molecularly identified reticular neuron populations to posture, however, has remained unclear. We investigated CaMKIIa-expressing reticular neurons (CaMKIIa-RNs) in the caudal medulla and their role in postural regulation. Using chemogenetic activation and inactivation in mice, we found that unilateral activation of CaMKIIa-RNs produced ipsilateral roll tilt of the head and trunk, driven by flexion/adduction of ipsilateral limbs and extension/abduction of contralateral limbs. This tilt was actively stabilized on a tilting platform and maintained during locomotion. In contrast, unilateral inactivation evoked opposite effects. Histological analysis revealed that CaMKIIa-RNs include reticulospinal neurons projecting via the ipsilateral lateral funiculus to the intermediate gray matter of the spinal cord. While both excitatory and inhibitory neurons are present, excitatory neurons predominate. Our results demonstrate that CaMKIIa-RNs in the caudal medulla are essential for maintaining dorsal-side-up orientation in diverse environments. Their left/right symmetry supports stability on horizontal surfaces, whereas asymmetry enables compensation on inclined surfaces, underscoring their key role in supraspinal control of posture.
© 2025. The Author(s).