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.
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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)