Ethological learning during the critical period resets synaptic setpoints in mouse binocular visual cortex

Critical periods are developmental windows that allow experience-dependent refinement of neuronal circuitry and function. While the consequences of sensory deprivation or alteration during the visual critical period have been well characterized, the impact of ethological experiences requiring active interaction with the sensory world is largely unexplored. Here, we use prey capture learning to assess structural and functional plasticity associated with visual learning in the primary visual cortex of critical-period mice. We show that prey capture learning supports improved temporal frequency discrimination and profoundly remodels visual circuitry by increasing spine turnover and moving spine density across the dendritic arbors of pyramidal neurons to new stable values. This widespread and persistent rewiring is absent in adults and supported by tumor necrosis factor α (TNF-α)-dependent homeostatic plasticity that contributes to behavioral improvement. Ethological critical period learning can thus co-opt homeostatic mechanisms to reset synaptic weight bounds to enable widespread synaptic remodeling to support improved visual function and behavior.