Proximo-distal gradient of spinal recurrent inhibition: implications for motor pool fractionation and dexterity

Spinal recurrent inhibition (RI), mediated by Renshaw cells, exhibits a highly conserved proximal-to-distal gradient across mammals: it is robust in proximal motoneuron (MN) pools but absent in MNs innervating both extrinsic and intrinsic digit muscles. Although this organizational pattern has been recognised for more than six decades, its mechanistic basis has remained unexplained. The widely accepted view that the gradient reflects the evolutionary emergence of monosynaptic corticomotoneuronal (CM) projections is challenged by the cat, which lacks monosynaptic CM input to digit MNs yet exhibits the same RI gradient observed in primates. We performed a comparative quantitative analysis of 16 published MN pools from humans, macaque monkeys, and cats. Four nested nonlinear regression models and a Bayesian hierarchical errors-in-variables model were used to evaluate the relative contributions of CM input and recurrent collateral density to normalised RI strength. The robustness of the CM contribution was assessed through Bayesian prior sensitivity analyses using both HalfNormal and symmetric Normal priors. Recurrent collateral density provided the strongest explanation for the conserved RI gradient, accounting for 97.7% of the cross-species variance (NLS R² = 0.977; ΔAIC = 53.6 relative to the CM-only model; Bayesian R² ≈ 0.975). Bayesian analyses consistently supported a positive, although quantitatively modest, contribution of CM input across all prior specifications, indicating that direct corticospinal connectivity refines but does not determine the distribution of RI. The cat therefore constitutes a decisive natural experiment demonstrating that the conserved RI gradient cannot be explained by the presence or absence of monosynaptic CM projections alone. These findings support the Motor Pool Fractionation Hypothesis (MPFH). Recurrent inhibition retains its established physiological role in regulating motoneuronal excitability and motor output; however, its selective anatomical distribution across motor pools appears to have an additional organizational significance. The absence of RI from digit MN pools creates a permissive spinal substrate for motor-pool fractionation, whereas the presence of direct CM connectivity represents a later evolutionary specialization that exploits and amplifies this pre-existing spinal organization to achieve highly fractionated motor control. The marked difference between human hand and foot dexterity is therefore interpreted as reflecting differences in corticospinal network coverage rather than differences in the spinal inhibitory substrate itself.