REGULATED NEUROTROPHIN RECEPTOR RESPONSIVENESS DURING NEURONAL MIGRATION AND EARLY DIFFERENTIATION

The response of brain tissue to neurotrophins during rat development w as examined using a novel in vitro assay for Trk/neurotrophin receptor activity. In this assay, brain tissues were exposed to neurotrophins and ligand-induced Trk tyrosine phosphorylation was measured. During t he perinatal period, Trk tyrosine phosphorylation in all brain areas w as induced very similarly by the TrkB and TrkC ligands brain-derived n eurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5). In the adult brain, minimal signals were observed after tre atment with these three factors, despite the continued presence of ful l-length and truncated TrkB protein. In contrast, responsiveness to th e TrkA ligand NGF was absent in the embryo and increased during the fi rst 2 weeks after birth in various brain areas, particularly in striat um, basal forebrain, and hippocampus. Our results, showing maximal res ponsiveness of brain tissue to BDNF, NT-3, and NT-4/5 during early neu ronal differentiation and migration, suggest involvement of TrkB in th ese events. The lack of a significant response to these neurotrophins in the adult brain indicates effective posttranslational mechanisms th at control the response of Trk family receptors. Our findings further demonstrate that neurons of the striatum and basal forebrain remain NG F responsive in the adult, confirming at the molecular level results o btained earlier at the cellular level for the basal forebrain choliner gic neurons.