The expression of neurotrophins and their trk receptors will be analyse in normal and experimentally manipulated rats. X-irradiated rats retain the immature, multiple inferior olive-Purkinje cell (IO-PC) innervation and can be studied throughout postnatal development. A localised retention of multiple IO-PC innervation can be induced by chronic application of D,L-2-amino-5-phosphonovaleric acid using Elvax implants. Neurotrophin and trk receptor expression will be detected in the 10 and cerebellum of these rats by reverse transcriptase polymerase chain reaction and in situ hybridization.
The mutant mice Lurcher (+/Lc) and Purkinje cell degeneration (pad) wil be used to study the target-dependent survival of 10 neurons. Both mutants suffer a complete loss of Purkinje cells during postnatal development (+/Lc abnormalities from P8 onwards, pad from P18) that leads to an indirect loss of 10 neurons following the loss of target. Neurotrophin(s) will be chronically applied to the cerebellum of these mutants during development using Elvax implants. IO and PC survival and morphology will be analysed in the adults.