Sex-dependent plasticity of adult neural tissue in response to damage

Plasticity of intact adult neural tissue in the vicinity of neural damage serves to restore functionality of circuits. Much remains to be learned about the mechanisms regulating this process and the reported sex differences in recovery outcomes. Here, we present the fly gut and its innervation as a simplified model to address these questions. We show that gut damage caused by ingestion of toxic agents resulted in plasticity of the adult enteric neuronal network, manifested as a Reactive Oxygen Species (ROS)-dependent increase in neural tissue, which was reversible after a recovery period. Interestingly, males did not display neural plasticity, and masculinization of neurons in females suppressed the damage-dependent neural growth. Together, these findings position the fly gut as a system to investigate the cellular, molecular, and sex-specific underpinnings of neural plasticity, with implications for therapeutic advancements in neural circuit recovery.