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

Using confocal laser scanning microscopy and immunohistochemistry, this stu dy shows the complete morphological development of GABAergic synaptic conta cts between Purkinje cells and neurons of the deep cerebellar nuclei of the mouse. Firstly, presynaptic varicosities visualized with antibodies agains t synaptophysin, synapsin or glutamic acid decarboxylase, were detected whe n the postsynaptic GABAA receptors were not yet aggregated in the membrane but had a diffuse cytoplasmic distribution, which indicated a lead in matur ation of presynaptic terminals over target cells. Secondly, receptor aggreg ates developed suddenly after an initial week of diffuse expression and the se clusters matured into more numerous and larger synaptic aggregates. Duri ng this postsynaptic maturation, the presynaptic varicosities develop into numerous and well-defined spots. As soon as both pre- and postsynaptic clus ters were detectable, these sites are always colocalized. We therefore cons ider the aggregation of postsynaptic; receptor during development as a land mark of synapse formation. Our observations are consistent with a developmental model in which the pre synaptic neuron differentiates its axon before the target neuron expresses the mature form of its receptors on the membrane. The presynaptic neuron ca n therefore instruct the target neuron about the distribution and aggregati on of the postsynaptic receptors at the synapse. (C) 2001 IBRO. Published b y Elsevier Science Ltd. All rights reserved.