Inhibitory postsynaptic membrane specializations are formed in gephyrin-deficient mice.

Gephyrin is a major postsynaptic scaffolding protein at GABAergic and glycinergic inhibitory synapses. Gephyrin-deficient (geph(-/-)) mice die after birth due to disinhibition of motor and sensory pathways resulting from a lack of postsynaptic glycine receptor and GABA(A) receptor clusters. Here, immunoelectron and confocal microscopy revealed that postsynaptic membrane specializations are formed in the absence of gephyrin. First, in brainstem sections obtained from newborn geph(-/-) mice inhibitory nerve terminals identified by immunogold labeling of either the vesicular inhibitory amino acid transporter (VIAAT) or GABA were found to be apposed to postsynaptic membrane areas decorated by electron-dense material. Second, neuroligin-2, a membrane protein of inhibitory postsynapses, was clustered beneath glutamate decarboxylase 65 (GAD-65) positive nerve terminals in geph(-/-) hippocampal cultures. These results indicate that proteins other than gephyrin define the ultrastructure of inhibitory postsynaptic membrane specializations.