Resilience of A Learned Motor Behavior After Chronic Disruption of Inhibitory Circuits

• DOI: 10.7554/elife.106039
• Publication Date: 2025-04-23T14:30:27Z
• Authors: Zsofia Torok; Laura Luebbert; Jordan Feldman; Alison Duffy; Alexander A Nevue; Shelyn Wongso; Claudio V Mello; Adrienne Fairhall; Lior Pachter; Walter G Gonzalez; Carlos Lois
• Keywords: Resilience

Maintaining motor behaviors throughout life is crucial for an individual’s survival and reproductive success. The neuronal mechanisms that preserve behavior are poorly understood. To address this question, we focused on the zebra finch, a bird produces highly stereotypical song after learning it as juvenile. Using cell-specific viral vectors, chronically silenced inhibitory neurons in pre-motor nucleus called high vocal center (HVC), which caused drastic degradation. However, producing severely degraded vocalizations around 2 months, rapidly improved, animals could sing songs resembled original. In adult birds, single-cell RNA sequencing of HVC revealed silencing interneurons elevated markers microglia increased expression Major Histocompatibility Complex I (MHC I), mirroring changes observed juveniles during learning. Interestingly, adults restore their despite lesioning lateral magnocellular anterior neostriatum (LMAN), brain juvenile This suggests while molecular may overlap, utilize different recovery. Chronic acute electrophysiological recordings within its downstream target, robust archistriatum (RA), activity circuit permanently altered with higher spontaneous firing RA lower compared to control even had fully recovered. Together, our findings show complex learned can recover extended periods perturbed dynamics. These results loss tone be compensated by recovery partly local do not require circuits necessary