Persistence of heterotypical synapses in transplanted cerebellar cultures in the absence of functional glia.

Neonatal mouse cerebellar cultures depleted of granule cells and functional glia by exposure to cytosine arabinoside were transplanted with either granule cells and glia or with granule cells in the absence of functional glia. Myelination was evident in cultures transplanted with granule cells and glia, excess sprouted cortical neurites were reduced, Purkinje cells acquired astrocytic sheaths and had a near normal complement of axosomatic synapses, and homotypical parallel fiber-Purkinje cell dendritic spine synapses were present in a 2.4:1 ratio to heterotypical recurrent axon collateral-Purkinje cell dendritic spine synapses. Cultures transplanted with granule cells were not myelinated, sprouted cortical neurites were not reduced. Purkinje cells lacked astrocytic sheaths and their somata remained hyperinnervated, and the ratio of homotypical to heterotypical dendritic spine synapses was 1.4:1. In the absence of functional glia there was a greater persistence of heterotypical recurrent axon collateral-Purkinje cell dendritic spine synapses. These results are consistent with a previously described astrocytic role in the regulation of axosomatic synapse density on glially ensheathed neurons, and suggest astrocytic participation in the reduction of heterotypical axospinous synapses. Astrocyte-mediated synapse reduction may be an important mechanism for circuit reorganization after transplantation or during development.