Protein differences associated with the absence of granule cells in the cerebella from the mutant weaver mouse and from X‐irradiated rat

The development of synaptic connections in the nervous systems of vertebrates [l] and invertebrates [2,3] is subject to a stringent genetic determinism which governs, for instance, the differentiation and migration of neurons, the growth of their processes and the selective recognition between preand postsynaptic surfaces. Nevertheless, there exists some evidence that the final connectivity and the functional state of some particular synapses, in both central and peripheral nervous systems, might be modulated by their activity at critical stages of development (see ref. 14751). In spite of its complex structure, the cerebellum constitutes a particularly suitable region of the brain to study these processes and, in particular, to distinguish between genetic and ‘epigenetic’ [5] phenomena. Its anatomy is rather well understood [6,8] ; the electrophysiological activity of single neurons can be recorded [6,9] ; most of its development occurs postnatalIy and becomes therefore easily accessible to the experiment; it contains only a few classes of cells but these cells are repeated a large number of times and therefore amenable to direct biochemical analysis. In the mouse, a number of mutations have been identified and mapped which lead to profound alterations of cerebellum anatomy [lo] and therefore of its physiology [ 111. In addition, one can induce some phenocopies of these mutations, such as the lack of granule cells, by drug injection [ 12-151, infection with specific viruses [ 161 or X-irradiation [ 17,181. In this paper, we describe experiments done with agranular cerebella from both the mutant weaver (WV) mouse [ 19-241 and X-irradiated rats. The electrophoretie patterns of the proteins solubilised from subcellular fractions of these cerebella are compared with those obtained with normal mouse and rat. Striking differences are noticed and, by comparison with the patterns obtained with a preparation of purified rat granule cells, assigned to the lack of granule cells.