Sub-second Three-dimensional Behavioral Profiling Reveals a Shared Rearing-descent Deficit and Lesion-aligned Lateralization in Parkinsonian Mice

Parkinson's disease (PD) is expressed through heterogeneous pathological processes, yet preclinical behavioral assays often reduce motor impairment to coarse measures of activity or task performance. Combining AVATAR-based three-dimensional pose tracking with keypoint-MoSeq behavioral segmentation, we longitudinally compared mice with unilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesions and mice with bilateral nigral human A53T α-synuclein overexpression with WT mice and directly with each other. Histology confirmed asymmetric nigrostriatal dopaminergic degeneration in 6-OHDA mice and bilateral midbrain dopaminergic loss with phosphorylated α-synuclein pathology in A53T mice. Although total distance traveled did not differ among the groups, both models showed reduced vertical movement with reduced use and weakened execution of a rearing-associated fast-descent syllable. This deficit did not differ between the models, and the transition from high rearing into this syllable remained reduced at the later timepoint in both models. Within A53T mice, the deficit was associated with residual nigral dopaminergic cell density. 6-OHDA mice showed lesion-aligned lateral-flexion and rotational biases in both syllable usage and within-syllable execution, and most direct differences between the models involved directionally biased syllables. In mice assessed at both timepoints, the lateral bias of 6-OHDA mice decreased within animals, whereas the rearing-descent deficit showed no detectable recovery. These findings identify a rearing-descent deficit shared by two Parkinsonian models that is not captured by global locomotor output, and show that three-dimensional syllable analysis resolves a unilateral lesion into altered syllable usage and biased within-syllable execution.