Recovery of a learned behavior despite partial restoration of neuronal dynamics after chronic inactivation of inhibitory neurons.

Maintaining motor skills is crucial for an animal's survival, enabling it to endure diverse perturbations throughout its lifespan, such as trauma, disease, and aging. What mechanisms orchestrate brain circuit reorganization and recovery to preserve the stability of behavior despite the continued presence of a disturbance? To investigate this question, we chronically silenced a fraction of inhibitory neurons in a brain circuit necessary for singing in zebra finches. Song in zebra finches is a complex, learned motor behavior and central to reproduction. This manipulation altered brain activity and severely perturbed song for around two months, after which time it was precisely restored. Electrophysiology recordings revealed abnormal offline dynamics, resulting from chronic inhibition loss, some aspects of which returned to normal as the song recovered. However, even after the song had fully recovered, the levels of neuronal firing in the premotor and motor areas did not return to a control-like state. Single-cell RNA sequencing revealed that chronic silencing of interneurons led to elevated levels of microglia and MHC I, which were also observed in normal juveniles during song learning. These experiments demonstrate that the adult brain can overcome extended periods of abnormal activity, and precisely restore a complex behavior, without recovering normal neuronal dynamics. These findings suggest that the successful functional recovery of a brain circuit after a perturbation can involve more than mere restoration to its initial configuration. Instead, the circuit seems to adapt and reorganize into a new state capable of producing the original behavior despite the persistence of some abnormal neuronal dynamics.

Quantifying mechanical and metabolic interdependence between speed and propulsive force during walking.

Walking speed is a useful surrogate for health status across the population. Walking speed appears to be governed in part by interlimb coordination between propulsive (FP) and braking (FB) forces generated during step-to-step transitions and is simultaneously optimized to minimize metabolic cost. Of those forces, FP generated during push-off has received significantly more attention as a contributor to walking performance. Our goal was to first establish empirical relations between FP and walking speed and then to quantify their effects on metabolic cost in young adults. To specifically address any link between FP and walking speed, we used a self-paced treadmill controller and real-time biofeedback to independently prescribe walking speed or FP across a range of condition intensities. Walking with larger and smaller FP led to instinctively faster and slower walking speeds, respectively, with ~80% of variance in walking speed explained by FP. We also found that comparable changes in either FP or walking speed elicited predictable and relatively uniform changes in metabolic cost, together explaining ~53% of the variance in net metabolic power and ~14% of the variance in cost of transport. These results provide empirical data in support of an interdependent relation between FP and walking speed, building confidence that interventions designed to increase FP will translate to improved walking speed. Repeating this protocol in other populations may identify other relations that could inform the time course of gait decline due to age and disease.