In addition to neuronal cell loss, a general reduction in the numbers of both excitatory and inhibitory synapses was observed in the neuropil of Pcdhgdel/del spinal cords using generic synaptic markers (Wang et al., 2002b; Weiner et al., 2005). It was unclear, however, whether all synapses are similarly affected, or if certain types are spared or even increased in number. To distinguish between these possibilities, we examined major classes of synaptic inputs onto motor neurons, a cell type that receives defined synaptic inputs and survives in both Pcdhgtcko/tcko and Pcdhgdel/del mutants. Four type-specific pre-synaptic markers were used, which respectively label synaptic vesicular transporters for the neurotransmitters GABA and glycine (VGAT), glutamate (VGLUT1 and VGLUT2), and acetylcholine (VAChT). We found that the average linear density of VGAT+ contacts was markedly decreased in both Pcdhgtcko/tcko and Pcdhgdel/del mutants (Figures 2J–J”, 2O), whereas the number of VGLUT1+ proprioceptive primary afferent inputs was surprisingly increased, more than double the number in wild type controls (Figures 2K-K”, 2O). By contrast, the densities of VGLUT2+ and VAChT+ contacts on motor neurons remain constant (Figures 2L-M, 2O). As expected, all four types of synapses are unaltered in Pcdhgtako/tako mutants (Figures 2O and S2C).
