Role of the target in synapse elimination: studies in cerebellum of developing lurcher mutants and adult chimeric mice.

As the mature nervous system is sculpted out of its embryonic anlage, regressive events are a surprisingly common feature. As one example, the establishment of adult innervation in the CNS and PNS often involves a massive withdrawal of previously formed functional synapses. In the cerebellum, the one-to-one relationship of inferior olivary climbing fibers to Purkinje cells is preceded by a transient stage in which each Purkinje cell is multiply innervated. The regulation of this regressive event is still not fully understood; previous studies suggested that some stimulus from the maturing granule cells is necessary. We have used the lurcher (Lc) mutation as a model system in which to study this phenomenon. In lurcher mice, Purkinje cells degenerate during the first few postnatal weeks, after receiving synaptic contacts from both inferior olivary neurons and granule cells. We have recorded the climbing fiber responses both in lurcher mutants at postnatal days 14-20 (P14-P20) and in adult lurcher chimeras. In the latter, experimental genetics are used to create a situation in which untreated wild-type Purkinje cells are present in an environment that ranges from 100% wild-type to nearly mutant. We found that in P14-P16 lurcher mutants, most of the cells recorded (75%) remained polyinnervated, whereas in wild-type control mice, only 10% of the Purkinje cells retained their multiple innervation. By P18-20, it was difficult to find Purkinje cells in the lurcher mutants that would withstand an intracellular electrode. Nonetheless, in those cells that were successfully impaled, most remained multiply innervated. By this age in wild-type mice, 100% of the Purkinje cells are monoinnervated.(ABSTRACT TRUNCATED AT 250 WORDS)