Environmental Enrichment Effects on Development of Retinal Ganglion Cell Dendritic Stratification Require Retinal BDNF

PLOS ONE, Apr 2007

A well-known developmental event of retinal maturation is the progressive segregation of retinal ganglion cell (RGC) dendrites into a and b sublaminae of the inner plexiform layer (IPL), a morphological rearrangement crucial for the emergence of the ON and OFF pathways. The factors regulating this process are not known, although electrical activity has been demonstrated to play a role. Here we report that Environmental Enrichment (EE) accelerates the developmental segregation of RGC dendrites and prevents the effects exerted on it by dark rearing (DR). Development of RGC stratification was analyzed in a line of transgenic mice expressing plasma-membrane marker green fluorescent protein (GFP) under the control of Thy-1 promoter; we visualized the a and b sublaminae of the IPL by using an antibody selectively directed against a specific marker of cholinergic neurons. EE precociously increases Brain Derived Neurotrophic Factor (BDNF) in the retina, in parallel with the precocious segregation of RGC dendrites; in addition, EE counteracts retinal BDNF reduction in DR retinas and promotes a normal segregation of RGC dendrites. Blocking retinal BDNF by means of antisense oligos blocks EE effects on the maturation of RGC dendritic stratification. Thus, EE affects the development of RGC dendritic segregation and retinal BDNF is required for this effect to take place, suggesting that BDNF could play an important role in the emergence of the ON and OFF pathways.

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Environmental Enrichment Effects on Development of Retinal Ganglion Cell Dendritic Stratification Require Retinal BDNF

Berardi N (2007) Environmental Enrichment Effects on Development of Retinal Ganglion Cell Dendritic Stratification Require Retinal BDNF. PLoS ONE 2(4): e346. doi:10.1371/journal.pone.0000346 Environmental Enrichment Effects on Development of Retinal Ganglion Cell Dendritic Stratification Require Retinal BDNF Silvia Landi 0 1 Maria Cristina Cenni 0 1 Lamberto Maffei 0 1 Nicoletta Berardi 0 1 0 Academic Editor: Rachel Wong, University of Washington , United States of America 1 1 Scuola Normale Superiore , Pisa , Italy , 2 Istituto di Neuroscienze del Consiglio Nazionale delle Ricerche (CNR) , Pisa, Italy, 3 Dipartimento di Psicologia , Universita` di Firenze , Florence , Italy A well-known developmental event of retinal maturation is the progressive segregation of retinal ganglion cell (RGC) dendrites into a and b sublaminae of the inner plexiform layer (IPL), a morphological rearrangement crucial for the emergence of the ON and OFF pathways. The factors regulating this process are not known, although electrical activity has been demonstrated to play a role. Here we report that Environmental Enrichment (EE) accelerates the developmental segregation of RGC dendrites and prevents the effects exerted on it by dark rearing (DR). Development of RGC stratification was analyzed in a line of transgenic mice expressing plasma-membrane marker green fluorescent protein (GFP) under the control of Thy-1 promoter; we visualized the a and b sublaminae of the IPL by using an antibody selectively directed against a specific marker of cholinergic neurons. EE precociously increases Brain Derived Neurotrophic Factor (BDNF) in the retina, in parallel with the precocious segregation of RGC dendrites; in addition, EE counteracts retinal BDNF reduction in DR retinas and promotes a normal segregation of RGC dendrites. Blocking retinal BDNF by means of antisense oligos blocks EE effects on the maturation of RGC dendritic stratification. Thus, EE affects the development of RGC dendritic segregation and retinal BDNF is required for this effect to take place, suggesting that BDNF could play an important role in the emergence of the ON and OFF pathways. - INTRODUCTION One of the most remarkable features of visual system parallel processing is the functional segregation of ON and OFF pathways originating in the retina [13]. This functional segregation has an anatomical correspondence in the stratification of the dendrites of ON- and OFF-center RGCs in different sublaminae of the IPL, sublamina a and b. It is well known that this segregated pattern of arborizations is achieved by a progressive restriction of RGC dendrites from bistratified processes into monostratified arborizations during retinal development [4]. The factors regulating this striking morphological rearrangement are not known, although glutamatergic [3,5] and cholinergic transmission [6] and visually driven activity [7] have been demonstrated to play a role. Our recent studies [8] have shown that an increased stimulation, such as that provided by EE, can affect the development of retinal visual responses. Whether RGC dendritic segregation is sensitive to the experience provided by EE is not known. Landi et al. [8] also found that EE precociously increases BDNF expression in the retina and that these higher levels of BDNF are crucial for triggering retinal functional development, suggesting an involvement of retinal BDNF in the experience-dependent maturation of retinal circuitry. In the present study we investigated whether the developmental remodelling of RGC dendrites is sensitive to the experience provided by EE and whether BDNF is involved in mediating EE effects. We found that EE accelerates the developmental segregation of RGC dendritic arborizations and counteracts the blockade of this process induced by DR. EE precociously increases BDNF in the retina, in parallel with the precocious segregation of RGC dendrites; moreover, EE counteracts retinal BDNF reduction caused by DR. Blocking retinal BDNF expression by means of antisense oligonucleotide injections in EE animals prevents EE from accelerating RGC dendritic developmental segregation. These results show that the developmental transition of RGC dendrites from the initial bistratified to the final monostratified pattern is sensitive to environmental experience, and identifies retinal BDNF as a key factor mediating experience effects on RGC maturation. Segregation of RGC dendritic stratification We analysed the segregation of RGC dendrites in bistratified and monostratified processes into a and b sublaminae of the IPL at different ages after birth. We used a transgenic line of mice expressing plasma-membrane marker green fluorescent protein (mGFP) under control of Thy-1 promoter [9]. GFP consistently labels dendrites, somata and axons of the RGCs, as shown in Fig. 1A. We visualized and quantified the stratification pattern of RGCs in retinal vertical sections (Fig. 1F, 1G, 1H) for all ages and also in whol (...truncated)


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Silvia Landi, Maria Cristina Cenni, Lamberto Maffei, Nicoletta Berardi. Environmental Enrichment Effects on Development of Retinal Ganglion Cell Dendritic Stratification Require Retinal BDNF, PLOS ONE, 2007, Volume 2, Issue 4, DOI: 10.1371/journal.pone.0000346