Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition

Abstract

Loss of visual acuity caused by abnormal visual experience during development (amblyopia) is an untreatable pathology in adults. We report that environmental enrichment in adult amblyopic rats restored normal visual acuity and ocular dominance. These effects were due to reduced GABAergic inhibition in the visual cortex, accompanied by increased expression of BDNF and reduced density of extracellular-matrix perineuronal nets, and were prevented by enhancement of inhibition through benzodiazepine cortical infusion.

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Figure 1: Environmental enrichment promotes amblyopia recovery and reduces intracortical inhibition in adult rats.
Figure 2: Recovery from amblyopia in environmental enrichment is due to a reduced GABAergic inhibition in the visual cortex, accompanied by increased BDNF expression and reduced density of PNNs.

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Acknowledgements

We thank F. Clementi for kindly providing us the diazepam and A. Viegi for his technical assistance with high-performance liquid chromatography. This work was supported by grants from Ministero dell'Università e della Ricerca (MIUR), Programmi di Ricerca di Rilevante Interesse Nazionale (PRIN) and Fondo Integrativo Speciale Ricerca (FISR).

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Authors

Contributions

A.S. and J.F.M.V. contributed equally to this work. A.S. carried out the in vivo electrophysiology, behavioral experiments, immunohistochemistry and assisted in the in vivo brain microdialysis. J.F.M.V. carried out the in vivo brain microdialysis, high performance liquid chromatography and assisted in the in vivo electrophysiology. P.M. carried out the in vivo electrophysiology and M.C.C., the immunohistochemistry experiments. L.B. performed the behavioral assessment of visual acuity in normal rats and R.D.P., the in vitro electrophysiology. A.S., J.F.M.V. and L.M. wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Alessandro Sale.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Visual acuity recovery in RS-EE adult rats. (PDF 22 kb)

Supplementary Fig. 2

Levels of extracellular glutamate are not different between RS-SC and RS-EE adult rats. (PDF 61 kb)

Supplementary Fig. 3

Environmental enrichment–induced changes of plasticity factors in the visual cortex. (PDF 391 kb)

Supplementary Methods (PDF 122 kb)

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Sale, A., Maya Vetencourt, J., Medini, P. et al. Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition. Nat Neurosci 10, 679–681 (2007). https://doi.org/10.1038/nn1899

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