The role of neurotrophins in developmental cortical plasticity

Abstract

Purpose - It has been proposed that experience dependent maturation and reorganization in the neocortex might be based on the activity dependent competition between different sets of axons for growth related molecules such as neurotrophins. In the present study we tested this hypothesis by examination of the effects of external administration of NGF and BDNF on the experience dependent rearrangement of thalamocortical connections after monocular deprivation (MD) in the developing cat visual cortex. Methods - The visual cortices of kittens were infused intracortically either with BDNF, NGF or cytochrome C while the animals were subjected to MD for one week during the peak of the critical period (postnatal day 26 to postnatal day 40). Subsequently cortical neuronal responses were assessed with optical (optical imaging of intrinsic signals) and single unit recording techniques. Results - In control hemispheres treated with cytochrome C, MD had caused the expected shift of OD towards the normal eye. Also hemispheres treated with NGF exhibited a strong shift of OD towards the open eye. However, in the BDNF infused hemispheres OD had shifted towards the deprived eye in a zone extending 2.5-3.5 mm from the infusion cannula and neurons had lost their orientation selectivity. In an adjacent transition zone both eyes activated the cortex equally well and responses were again tuned for orientation and at still larger distances OD was shifted towards the normal eye. Conclusions - The present data support the concept of an involvement of neurotrophins in cortical plasticity. However, our observations suggest for both neurotrophins, NGF and BDNF, a more complex role in the developing neocortex than serving simply as the substrate of an activity dependent competition process within the visual cortex. Moreover, the outcome of our study indicates strong differences between BDNF and NGF concerning their involvement and locus of action in developmental plasticity.