Synapse elimination in olivo-cerebellar explants occurs during a critical period and leaves an indelible trace in Purkinje cells

During developmental synaptogenesis, the pre- and postsynaptic cells undergo specific interactions that lead to the establishment of the mature circuit. We have studied the roles of the pre- and postsynaptic cells in establishing this mature innervation by using an in vitro model of synaptic development. We describe climbing fiber (CF)-Purkinje cell (PC) synaptogenesis in cultured mouse hindbrain explants and show that synaptic competition occurs during early development in vitro. By manipulating the maturation stage of each of the synaptic partners in a coculture experimental paradigm, we found that multi-innervation does not occur when both synaptic partners are mature and have already experienced synapse elimination; in contrast, mature PCs can be multi-innervated when they have never experienced synapse elimination and/or when CFs are immature. However in these cases, the normal process of synapse elimination is impaired. These results show that CF-synapse elimination occurs only during a PC-dependant critical period and triggers indelible signals that prevent synapse competition in the mature system.