A novel behavioral paradigm for characterizing anticipatory postural adjustments in mice

Voluntary movements perturb the body's equilibrium, and the nervous system limits this disturbance by generating anticipatory postural adjustments (APAs) that redistribute body weight before and during movement. APAs have been characterized extensively in humans and larger animal models, but the absence of a tractable behavioral assay in mice has limited access to the genetic and circuit-level tools needed to investigate their neural basis. Here, we describe a force-plate behavioral paradigm in which freely moving mice stand on four independent load cells, receive an auditory GO cue and initiate locomotion voluntarily without task-specific training. Using force recordings, high-speed video and markerless pose estimation, we show that mice initiate a step with a stereotyped sequence of weight shifts: the center of pressure (CoP) moves anteriorly and then laterally away from the swing side, the swing forepaw and diagonally opposite hindpaw unload, and body weight is carried by the remaining diagonal pair. A single principal component explained approximately 80% of the variance in the average trial, compared with approximately 50% when paw identity was shuffled. Pressure recordings identified rapid swing-forepaw unloading beginning, on average, 87.9 ms before lift-off. Head and ear movement began approximately 200 ms before lift-off, and an operational multimodal estimate placed the interval between the earliest detected postural movement and the onset of forepaw rotation at approximately 160-180 ms. Neuropixels recordings from the pontine reticular nucleus (PRN) and supplementary motor area (SMA), monosynaptic tracing of inputs to reticulospinal PRN neurons, and preliminary cell-ablation experiments identify the PRN as a candidate node in the circuitry supporting anticipatory postural control. This paradigm provides a platform for circuit-level investigation of postural control and its disruption in disease.