PT  - JOURNAL ARTICLE
AU  - Peta Eggins
AU  - James Blok
AU  - Justin Petersen
AU  - Larissa Savvas
AU  - Lara Rogerson-Wood
AU  - Hannan Mansuri
AU  - Atomu Sawatari
AU  - Catherine A. Leamey
TI  - Environmental enrichment partially repairs subcortical mapping errors in Ten-m3 knockout mice during an early critical period
AID  - 10.1523/ENEURO.0478-18.2019
DP  - 2019 Nov 25
TA  - eneuro
PG  - ENEURO.0478-18.2019
4099  - http://www.eneuro.org/content/early/2019/11/25/ENEURO.0478-18.2019.short
4100  - http://www.eneuro.org/content/early/2019/11/25/ENEURO.0478-18.2019.full
AB  - 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 knockout (KO) mice exhibit a highly-stereotyped and profound miswiring of ipsilateral retinogeniculate axons and associated deficits in binocularly-mediated visual behaviour. We determined whether, and when, EE can drive the repair of subcortical wiring deficits by analysing Ten-m3 KO and wildtype mice that were enriched for 6 weeks from adulthood, weaning or birth in comparison to standard-housed 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 enriched from birth. No EE-induced correction of mistargeted axons was observed at postnatal day 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, 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.Significance Statement The incorrect wiring of neural circuits can lead to profound disability. Using a mouse model which exhibits a marked miswiring of neural projections to subcortical relay centres of the brain, we show that positive modulation (enrichment) of the environment during the first few postnatal weeks can induce the pruning of aberrant neural projections. The capacity for environmental enrichment to correct miswired projections diminished prior to adolescence, suggesting that the enrichment can only drive these changes during an early critical period. This expands our knowledge of the capacity for enrichment to induce repair of neural circuits. The demonstration of dramatic effects on targeting of neural projections over a restricted period may have implications for the development of therapies for neurodevelopmental disorders.