Environmental enrichment (EE) has been shown to improve neural function via the regulation of cortical plasticity. Its capacity to induce functional and/or anatomical repair of miswired circuits is unknown. Ten-m3 knock-out (KO) mice exhibit a highly stereotyped and profound miswiring of ipsilateral retinogeniculate axons and associated deficits in binocularly-mediated visual behavior. We determined whether, and when, EE can drive the repair of subcortical wiring deficits by analyzing Ten-m3 KO and wild-type (WT) mice that were enriched for six weeks from adulthood, weaning or birth in comparison to standard-housed (SE) controls. Six weeks of EE initiated from birth, but not later, induced a significant reduction in the area occupied by ipsilateral retinogeniculate terminals in KOs. No EE-induced correction of mistargeted axons was observed at postnatal day (P)7, indicating that this intervention impacts pruning rather than initial targeting of axons. This reduction was most prominent in the ventrolateral region of the dorsal lateral geniculate nucleus (dLGN), suggesting a preferential pruning of the most profoundly mistargeted axons. EE can thus partially repair a specific, subcortical axonal wiring deficit, but only during an early, developmentally-restricted time window.

Environmental enrichment (EE) has been shown to promote neural plasticity. Its capacity to induce functional repair in models which exhibit profound sensory deficits due to aberrant axonal guidance has not been well-characterized. Ten-m3 knockout (KO) mice exhibit a highly-stereotyped miswiring of ipsilateral retinogeniculate axons and associated profound deficits in binocularly-mediated visual behavior. We determined whether, and when, EE can drive functional recovery by analyzing Ten-m3 KO and wildtype (WT) mice that were enriched for 6 weeks from adulthood, weaning or birth in comparison to standard-housed controls. EE initiated from birth, but not later, rescued the response of Ten-m3 KOs to the "looming" stimulus (expanding disc in dorsal visual field), suggesting improved visual function. EE can thus induce recovery of visual behavior, but only during an early developmentally-restricted time-window.