The development of inhibitory synaptic specializations in the mouse deep cerebellar nuclei

Using confocal laser scanning microscopy and immunohistochemistry, this study shows the complete morphological development of GABAergic synaptic contacts between Purkinje cells and neurons of the deep cerebellar nuclei of the mouse. Firstly, presynaptic varicosities visualized with antibodies against synaptophysin, synapsin or glutamic acid decarboxylase, were detected when the postsynaptic GABA(A) receptors were not yet aggregated in the membrane but had a diffuse cytoplasmic distribution, which indicated a lead in maturation of presynaptic terminals over target cells. Secondly, receptor aggregates developed suddenly after an initial week of diffuse expression and these clusters matured into more numerous and larger synaptic aggregates. During this postsynaptic maturation, the presynaptic varicosities develop into numerous and well-defined spots. As soon as both pre- and postsynaptic clusters were detectable, these sites are always colocalized. We therefore consider the aggregation of postsynaptic receptor during development as a landmark of synapse formation. Our observations are consistent with a developmental model in which the presynaptic neuron differentiates its axon before the target neuron expresses the mature form of its receptors on the membrane. The presynaptic neuron can therefore instruct the target neuron about the distribution and aggregation of the postsynaptic receptors at the synapse.