Synaptic anchoring of glycine receptors in developing collicular neurons under control of metabotropic glutamate receptor activity

The role of GlyRs in supramedullar neurons is still enigmatic: although present in the plasma membrane, they seem to be excluded from synaptic transmission. Two distinct stages of inhibitory synaptogenesis in cultured collicular neurons were defined on the basis of strychnine sensitivity of IPSCs, presence of EPSCs, KCC2 expression, and transmitter-induced Ca2+ responses. In the absence of KCC2 and glutamatergic transmission, newborn VIAAT-labeled boutons contained GlyT2, released glycine, and accumulated postsynaptic gephyrin and GlyRs. With ongoing maturation, when neurons expressed KCC2 and displayed glutamatergic activity, inhibitory synapses contained GAD65, released GABA, and accumulated postsynaptic gephyrin and GABA(A)Rs, but not GlyRs. This activity- and transmitter-specific regulation of GlyR distribution could be challenged by chronic blockade of group I mGluRs. It is thus concluded that glutamatergic transmission can contribute to the regulation of synaptic GlyR stabilization during inhibitory synapse development.