Topographic organization of the olivocerebellar projection in normal and mutant mice

An intriguing question in development neurobiology is whether target cell position and number are important in determining the normal organization and distribution of an afferent projection to that target. The olivocerebellar projection provides an ideal system for such study since it possesses a high degree of specificity. Groups of cells in the inferior olivary complex (IO) provide climbing fiber (CF) afferents to Purkinje cells (PCs) in particular parasagittal zones. A further advantage in studying this projection system is the availability of a variety of neurological mutant mice with genetic defects in this primary target cell (i.e., the PC). Three mutants, reeler (rl/rl), weaver (wv/wv; wv/+), and staggerer (sg/sg), were chosen for this study because they have varying degrees of PC abnormalities including reduced numbers and ectopic PCs. To investigate this problem, three types of studies were carried out in normal and mutant mice; (1) a qualitative and quantitative light microscopic study of the IO to determine whether the IO is also abnormal in the mutants, (2) an autoradiographic study in normal mice involving single or multiple injections of 3H-L-leucine into the IO in an effort to resolve the controversial issue of whether the olivocerebellar projection terminates in a series of parasagittal bands with empty zones between labeled bands or if CFs supply PCs in all cerebellar regions, and (3) using a similar approach in the mutants (i.e., single injections of 3H-L-leucine into the IO) to determine what effects abnormal target cell position and number have on olivocerebellar organization and topography