NEUROTROPHIN-3 PROMOTES CEREBELLAR GRANULE CELL EXIT FROM THE EGL

In the cerebellum, the mRNAs for neurotrophin-3 (NT-3) and its high-af finity tyrosine kinase receptor trkC are expressed by both the differe ntiated granule cells of the internal granule cell layer (IGL) and the ir precursors in the external germinal layer (EGL), We have investigat ed the effects of chronic application of exogenous NT-3 in vivo on cer ebellar granule cell genesis and differentiation. NT-3 was applied to the posterior surface of the rat cerebellum from P6 onwards using Elva x implants. At P10 the EGL of cerebellar lobules VII and VIII was sign ificantly reduced in thickness in NT-3 implanted rats when compared wi th controls, Immunocytochemical analysis of the EGL using antibodies t o proliferating cell nuclear antigen (PCNA) revealed that the number o f postmitotic, premigratory (PCNA-immunonegative) granule cell precurs ors was preferentially reduced in the NT-3 implanted rats. In situ DNA fragmentation labelling confirmed that this was not accompanied by in creased cell death in the EGL. These results suggest that NT-3 promote s the differentiation of postmitotic, premigratory granule cell precur sors, accelerating cell exit from the EGL.