Inhibitory synapses in the developing auditory system are glutamatergic

Activity-dependent synapse refinement is crucial for the formation of precise excitatory and inhibitory neuronal circuits. Whereas the mechanisms that guide refinement of excitatory circuits are becoming increasingly clear, the mechanisms guiding inhibitory circuits have remained obscure. In the lateral superior olive (LSO), a nucleus in the mammalian sound localization system that receives inhibitory input from the medial nucleus of the trapezoid body (MNTB), specific elimination and strengthening of synapses that are both GABAergic and glycinergic (GABA/glycinergic synapses) is essential for the formation of a precise tonotopic map. We provide evidence that immature GABA/glycinergic synapses in the rat LSO also release the excitatory neurotransmitter glutamate, which activates postsynaptic NMDA receptors (NMDARs). Immunohistochemical studies demonstrate synaptic colocalization of the vesicular glutamate transporter 3 with the vesicular GABA transporter, indicating that GABA, glycine and glutamate are released from single MNTB terminals. Glutamatergic transmission at MNTB-LSO synapses is most prominent during the period of synapse elimination. Synapse-specific activation of NMDARs by glutamate release at GABAergic and glycinergic synapses could be important in activity-dependent refinement of inhibitory circuits.