Biology subjects

Spence, A. J.

Publications and source records attributed to Spence, A. J..

3 recordsLinked to original sources

bioRxiv2026

Chemogenetic excitation and play promote functional recovery in juvenile spinal cord injury

Functional recovery after spinal cord injury depends on whether reorganizing descending circuits form adaptive, task-specific relays rather than maladaptive ones. The corticospinal tract undergoes competitive, activity-dependent refinement during a defined juvenile window, so the timing and polarity of cortical activity may dictate whether injured circuits rewire usefully. Whether biasing cortical activity during this window can steer reorganization toward recovery, and whether naturalistic rehabilitation supplies the activity such steering requires, remain unknown. In juvenile rats we delivered excitatory or inhibitory chemogenetic receptors, or a control vector, to the forelimb motor cortex at postnatal day 5, induced a right cervical hemisection at postnatal day 14, and gave oral clozapine-N-oxide during nightly rough-and-tumble play from postnatal day 20 to 50. Play, the rehabilitation common to all groups, did not differ between them, isolating cortical-activity polarity as the manipulated variable. Outcomes spanned forelimb dexterity, reaching kinematics, cortical output by intracortical microstimulation, descending architecture by intersectional viral tracing, and frequency-dependent depression of the Hoffmann reflex. In untreated injured animals, cortical output re-lateralized maladaptively toward the intact forelimb, driving the ipsilateral (intact) limb in 11 of 15 evoked responses and 3 of 5 animals. Excitation preserved selective drive to the impaired forelimb (38 of 39 responses; concordant-site proportion Kruskal-Wallis H = 9.08, exact P = 0.0031), and pure ipsilateral re-lateralization was absent from all nine treated animals (3 of 5 control versus 0 of 9 treated; Fisher's exact P = 0.027). Across behavioural, kinematic, and anatomical measures a consistent excitatory > control > inhibitory gradient emerged. Excitation enhanced wrist elevation and forward extension during reaching, restored frequency-dependent depression of the Hoffmann reflex, and selectively recruited three parallel lesion-bypassing relays: interhemispheric cortico-cortical-spinal, cortico-reticulo-spinal, and cortico-propriospinal (ipsilesional cortical relay neurons F(2,14) = 56.96, P < 0.0001). Inhibition yielded the weakest behavioural recovery and least relay recruitment, and did not restore contralesional cortical drive. Cortical-activity polarity during a juvenile window thus acts as a developmental switch governing whether descending reorganization is adaptive or maladaptive. Guided excitation, paired with behaviourally meaningful activity, reshapes diffuse sprouting into structured, lesion-bypassing relays and corrects the spontaneous re-lateralization that otherwise misdirects recovery. These findings provide a translational rationale for activity-paired neuromodulation in paediatric spinal cord injury.

neuroscience↗

bioRxiv2026

Kinematics-based assessment of reaching and grasping movements in LRN ablated animals identifies a role for the LRN in endpoint stabilization and reach timing.

The lateral reticular nucleus (LRN) is thought to contribute to skilled forelimb control but its specific contributions to reaching and grasping remain unclear. In this paper, we examine skilled reaching in intact adult female Long-Evans rats after bilateral LRN ablation through single-pellet reaching tasks. Tasks were analyzed using sensitive quantitative kinematic analyses and qualitative behavioral scoring. Overall, limb transport was largely preserved after ablation, with results appearing in temporally restricted differences. The clearest deficits emerged in pellet-directed endpoint control. LRN-ablated animals showed broad variability in end-point covariance, endpoint spread, and increased trial-to-trial variability, indicating that the movement became less precise and less consistent. These effects were more consistent than any single spatial difference seen, suggesting that ablation of the LRN impairs movement refinement rather than inducing a simple directional bias, although the paw height during the reach was significantly effected. Reach duration also changed, but this temporal difference emerged later and was less prominent. Our results suggest that the LRN acts as an important contributor to endpoint stabilization and reach timing during skilled forelimb behavior.

neuroscience↗

bioRxiv2022

Infrared videography of a subcutaneous knee tattoo as a simple and inexpensive method to overcome skin motion artifact in rodent kinematics

Kinematic analyses of rodent behavior are frequently used in neuroscience research, and commonly in spinal cord injury (SCI) studies. Unfortunately, skin motion artifact introduces significant errors into these data, because the skin is only loosely coupled to the underlying skeleton by connective tissue. In rats, these errors can be as large as 50-75%,as quantified by past work using x-ray fluoroscopy. Here we show that infrared videography of a subcutaneous tattoo can overcome skin motion artifact in rodent kinematics. The method yields data similar to gold standard x-ray fluoroscopy systems at a fraction of the cost, does not affect the animals locomotion, and results in markers that persist for at least 10 weeks. We found that, compared to a gold-standard x-ray fluoroscopy study that directly tracked the skeleton, our method reduced the error in mean hip angle from 17 {+/-} 6.0 to 3.1 {+/-} 2.4 degrees (mean {+/-} SEM), and the root-mean-square (RMS) error across the mean hip angle waveform from 20 to 5.3 degrees (n=4 rats). The knee joint angle waveform derived from infra-red imaging tightly matched the shape of the x-ray waveform after allowing for a constant offset, having RMS error reduced from 8.1 to 1.2 degrees. The method stands to significantly reduce between-animal errors, and hence between laboratory errors, in these ubiquitous model systems, especially important in SCI studies where individuals are assigned to different treatments.

neuroscience↗