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.