# Distinct descending and biomechanical influences on interlimb coordination in mice

**Authors:** Zane Mitrevica, Andrew J. Murray

PMC · DOI: 10.1016/j.isci.2026.115008 · 2026-02-16

## TL;DR

The study explores how mice coordinate their limbs during movement by using a new method to separate the effects of speed and body load.

## Contribution

A novel head-fixed locomotor paradigm was developed to study gait coordination in mice, decoupling speed and load effects.

## Key findings

- Hind-heavy loading causes a shift to more synchronized limb coordination.
- This coordination change is largely independent of movement speed.
- The effect aligns with changes in how limbs support the body.

## Abstract

Interlimb coordination, or gait, is a hallmark of locomotion, but has been challenging to study due to its partial dependence on speed and the difficulty of reliably evoking the full gait spectrum in genetically amenable quadrupeds such as mice. To address this, we developed a head-fixed locomotor paradigm that decouples the speed- and leg loading-related effects on gait by combining optogenetic stimulation in the cuneiform nucleus with head height and surface slope modulation. This approach revealed a largely speed-independent shift in homolateral phase preference from strict alternation to a quarter-of-phase more synchronized coordination upon a rearward redistribution of load. This load-related effect was observed regardless of hindlimb phase and aligned with changes in limb support patterns. These findings highlight how quadrupeds use biomechanical input to coordinate limbs across speeds and environments, and serve as an entry point to a behaviour-driven study of gait circuits.

•Speed- and leg load-related effects on interlimb coordination are explored in mice•Hind-heavy loading correlates with up to a quarter-phase homolateral synchronization•The effect is largely speed-independent and aligns with changes in support patterns

Speed- and leg load-related effects on interlimb coordination are explored in mice

Hind-heavy loading correlates with up to a quarter-phase homolateral synchronization

The effect is largely speed-independent and aligns with changes in support patterns

Biomechanics; Neuroscience

## Linked entities

- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Slc17a6 (solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 6) [NCBI Gene 140919] {aka 2900073D12Rik, DNPI, VGLUT2}, Eif1a (eukaryotic translation initiation factor 1A) [NCBI Gene 13664] {aka Ef1a, Eftu, Eif4c, eIF-1A, eIF-4C}, Chat (choline O-acetyltransferase) [NCBI Gene 12647] {aka B230380D24Rik, CHOACTase}
- **Diseases:** sensory-dependent (MESH:D019966), injury (MESH:D014947), burn (MESH:D002056)
- **Chemicals:** pentobarbital (MESH:D010424), Triton X- (MESH:D017830), RelyX (MESH:C528569), oxygen (MESH:D010100), isoflurane (MESH:D007530), C&amp;B (MESH:C063451), CoS (-), aluminum (MESH:D000535), DAPI (MESH:C007293), meloxicam (MESH:D000077239), paraformaldehyde (MESH:C003043)
- **Species:** Canis lupus familiaris (dog, subspecies) [taxon 9615], Mus musculus (house mouse, species) [taxon 10090], Felis catus (cat, species) [taxon 9685], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Lemur catta (Ring-tailed lemur, species) [taxon 9447], Drosophila melanogaster (fruit fly, species) [taxon 7227], Equus caballus (domestic horse, species) [taxon 9796]
- **Mutations:** H134R
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW), /6J — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_W797)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12962166/full.md

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Source: https://tomesphere.com/paper/PMC12962166