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

The plasticity of intact adult neural tissue in the vicinity of neural damage helps restore circuit function. 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 ingestion of damaging agents triggers a reversible increase in adult enteric neural tissue in females, consistent with growth rather than neurogenesis. This growth can be influenced by gut-derived reactive oxygen species, as suggested by suppression with an antioxidant. Interestingly, males do not display neural plasticity, and masculinization of neurons in females suppresses damage-dependent neural growth. Conversely, feminizing male neurons does not confer plasticity, suggesting that sex-specific cues from surrounding tissues may be required for this response. Blocking plasticity reduces the dextran sulfate sodium-induced increase in defecation and further shortens survival, indicating that female-specific neural plasticity supports both gut function and viability. Together, these findings establish a physiological model to dissect cellular, molecular and sex-dependent regulators of adult neural plasticity relevant to circuit repair.