Nutritional tryptophan restriction impairs plasticity of retinotectal axons during the critical period.

The use-dependent specification of neural circuits occurs during post-natal development with a conspicuous influence of environmental factors, such as malnutrition that interferes with the major steps of brain maturation. Serotonin (5-HT), derived exclusively from the essential aminoacid tryptophan, is involved in mechanisms of development and use-dependent plasticity of the central nervous system. We studied the effects of the nutritional restriction of tryptophan in the plasticity of uncrossed retinotectal axons following a retinal lesion to the contralateral retina during the critical period in pigmented rats. Litters were fed through their mothers with a low tryptophan content diet, based on corn and gelatin, a complemented diet with standard tryptophan requirements for rodents or standard laboratory diet. The results suggest a marked reduction in the plasticity of intact axons into denervated territories in the tryptophan restricted group in comparison to control groups. Tryptophan complementation between PND10-21 completely restored retinotectal plasticity. However, the re-introduction of tryptophan after the end of the critical period (between PND28-P41) did not restore the sprouting ability of uncrossed axons suggesting a time-dependent effect to the reversion of plasticity deficits. Tryptophan-restricted animals showed a reduced activity of matrix metalloproteinase-9 and altered expressions of phosphorylated forms of ERK1/2 and AKT. Our results demonstrate the influence of this essential aminoacid as a modulator of neural plasticity during the critical period through the reduction of serotonin content which alters plasticity-related signaling pathways and matrix degradation.

Neonatal tryptophan dietary restriction alters development of retinotectal projections in rats.

The specification of sensory neural circuits includes the elimination of transitory axon collaterals/synapses that takes place during early post natal life, an important step for the acquisition of topographical order of sensory systems. Serotonin has been implicated in the patterning of connections in subcortical and cortical circuits. We investigated the effects of the dietary restriction of the only serotonin precursor, tryptophan, on the development of the uncrossed retinotectal pathway in pigmented rats. Litters were fed through their mothers with either a tryptophan restricted, corn and gelatin based diet or a similar control diet complemented with tryptophan during the lactation period. The developmental status of the uncrossed retinotectal terminal fields was studied after the anterograde transport of horseradish peroxidase injected into one eye. We also studied the effects of tryptophan restriction on 5-HT immunoreactivity of raphe neurons, on cAMP levels in the visual layers of the superior colliculus and on protein synthesis among retinal neurons. We found that tryptophan restriction resulted in reduced weight gain among tryptophan restricted rats, without differences in protein synthesis between tryptophan complemented and restricted groups. Tryptophan restriction was also associated with a reduction of serotonin immunoreactive cells in the raphe nuclei and increased cAMP levels in the superior colliculus. Finally we found that neonatal tryptophan restriction resulted in an abnormal patterning of retinotectal topography, which was consistent with a developmental delay in axonal elimination and fine tuning of central connections. These results suggest, therefore, that dietary tryptophan is crucial for the influence of serotonin in the maturation of central visual connections.