Research reportFluoxetine-induced plasticity in the rodent visual system
Introduction
Serotoninergic axons have an extensive distribution in the central nervous system influencing cellular excitability and second messenger systems 6, 14with implications in synaptic plasticity 3, 30. In the visual system of mammals, it has been shown that serotonin influences use-dependent plasticity within the visual cortex and axon reorganization during development of the retinotectal projections 1, 8. In the rodent visual system, the development of serotoninergic innervation and synaptic profiles parallel the development of retinotectal axons 4, 23and the experimental expansion of serotoninergic innervation alters the retinotectal pathways [22].
The uncrossed retinotectal projections of neonatal (PND 1–10) and juvenile rats (PND 14–28) were used as an experimental model in the present study. The uncrossed pathway consists of a series of clusters of terminal labeling lying in the ventral aspect of the collicular visual layers 11, 26. This pattern emerges from a diffuse innervation observed in newborns which develops an adult-like pattern by postnatal day 10 [10]. Retinal lesions in young rats lead to a reorganization in the uncrossed pathway of the intact eye that tends to fill-in completely the denervated area 7, 12, 27. By the third postnatal week, however, a retinal lesion induces only minor rearrangements in the uncrossed pathway of the opposite eye which shows sparse sprouting of fibers toward the tectal surface [24].
In the present work we studied the effect of a chronic treatment with a serotonin reuptake inhibitor—fluoxetine—in the uncrossed retinotectal projection of rats. We studied both the normal distribution in neonatal and juvenile rats and the lesion-induced plasticity observed following a restricted retinal lesion in three-week-old rats (Fig. 1). We found that fluoxetine affects the development of topography in neonates and disrupts the organization of this projection in juvenile rats. Also, we show that fluoxetine amplifies the sprouting of intact axons following a unilateral retinal lesion in mature rats.
Section snippets
Materials and methods
We studied the retinotectal projections of pigmented Lister Hooded rats between birth and the fourth postnatal week when the retinotectal projections present an adult-like organization [10]. One group was submitted to a peripheral temporal retinal lesion on the third postnatal week (PND 21). We studied the development and the distribution of the uncrossed retinotectal pathway of the right eye in unoperated and operated animals following either fluoxetine or vehicle (NaCl 0.9%) treatment. The
Effect of fluoxetine on the organization of the uncrossed retinotectal pathway in juvenile and neonatal rats
The uncrossed retinotectal pathway of PND 28 unoperated rats were investigated in vehicle-treated and fluoxetine-treated rats. After vehicle treatment between PND 14–28, the uncrossed retinotectal projection presented, in coronal sections, a series of clusters of HRP terminal labeling distributed along the medio-lateral axis of the superior colliculus (Fig. 2A). Most of the terminal labeling was concentrated in the ventral border of the stratum griseum superficiale (SGS), as defined by the
Discussion
The present study showed that the chronic treatment with a selective serotonin reuptake inhibitor—fluoxetine—led to rearrangements in the retinotectal projection and to an amplification of the lesion-induced plasticity of the intact pathway. These effects were observed, respectively, in 33% of the unoperated animals and in 53% of the retinal lesion group. The partial effects here described can be explained both by the systemic treatment used in the present study and by the anterograde labeling
Acknowledgements
We acknowledge Maria da Conceição Paiva Silva for technical support and to Drs. Rafael Linden, Roberto Paes de Carvalho, Paula Campello-Costa and Ana Lúcia M. Ventura for the critical review of the manuscript. We also thank to Eli-Lilly do Brasil for providing fluoxetine for this study. Financial support: FINEP, PRONEX, FAPERJ, CNPq.
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