The significant decrease in VGAT+ synapses on motor neurons in both Pcdhgtcko/tcko and Pcdhgdel/del mutants is consistent with our observation that the two mutants display identical motor defects, which closely resemble those found in the VGAT (Wojcik et al., 2006), GAD67 (Asada et al., 1997), and Gephyrin (Feng et al., 1998) knockouts. Key features of the common phenotypes are muscle stiffness and immobility, which can be explained by tetanic motor neuron activation due to compromised inhibitory neurotransmission. The reduced density of VGAT+ contacts, as well as the normal numbers of VAChT+ synapses in Pcdhgtcko/tcko and Pcdhgdel/del mutants correlate well with the significant reduction of inhibitory interneurons and unaltered numbers of cholinergic partition cells in both mutants. By contrast, VGLUT2+ synaptic density is normal despite the reduction of certain premotor glutamatergic interneurons (e.g. Chx10+ V2a interneurons), which suggests that alternative neuronal sources or compensatory mechanisms might be involved in the development of these synapses.
