Synaptic and Nonsynaptic Localization of Protocadherin-γC5 in the Rat Brain

It has been proposed that gamma-protocadherins (Pcdh-gamma s) are involved in the establishment of specific patterns of neuronal connectivity. Contrary to the other Pcdh-gamma s, which are expressed in the embryo, Pcdh-gamma C5 is expressed postnatally in the brain, coinciding with the peak of synaptogenesis. We have developed an antibody specific for Pcdh-gamma C5 to study the expression and localization of Pcdh-gamma C5 in brain. Pcdh-gamma C5 is highly expressed in the olfactory bulb, corpus striatum, dentate gyrus, CA1 region of the hippocampus, layers I and II of the cerebral cortex, and molecular layer of the cerebellum. Pcdh-gamma C5 is expressed in both neurons and astrocytes. In hippocampal neuronal cultures, and in the absence of astrocytes, a significant percentage of synapses, more GABAergic than glutamatergic, have associated Pcdh-gamma C5 clusters. Some GABAergic axons show Pcdh-gamma C5 in the majority of their synapses. Nevertheless, many Pcdh-gamma C5 clusters are not associated with synapses. In the brain, significant numbers of Pcdh-gamma C5 clusters are located at contact points between neurons and astrocytes. Electron microscopic immunocytochemistry of the rat brain shows that 1) Pcdh-gamma C5 is present in some GABAergic and glutamatergic synapses both pre- and postsynaptically; 2) Pcdh-gamma C5 is also extrasynaptically localized in membranes and in cytoplasmic organelles of neurons and astrocytes; and 3) Pcdh-gamma C5 is also localized in perisynaptic astrocyte processes. The results support the notions that 1) Pcdh-gamma C5 plays a role in synaptic specificity and/or synaptic maturation and 2) Pcdh-gamma C5 is involved in neuron-neuron synaptic interactions and in neuron-astrocyte interactions, including perisynaptic neuron-astrocyte interactions. J. Comp. Neurol. 518:3439-3463, 2010. (C) 2010 Wiley-Liss, Inc.