Glutamatergic inputs and glutamate-releasing immature inhibitory inputs activate a shared postsynaptic receptor...

Principal cells of the lateral superior olive (LSO) compute interaural intensity differences by comparing converging excitatory and inhibitory inputs. The excitatory input carries information from the ipsilateral ear, and the inhibitory input carries information from the contralateral ear. Throughout life, the excitatory input pathway releases glutamate. In adulthood, the inhibitory input pathway releases glycine. During a period of major developmental refinement in the LSO, however, synaptic terminals of the immature inhibitory input pathway release not only glycine, but also GABA and glutamate. To determine whether glutamate released by terminals in either pathway could spill over to activate postsynaptic N-methyl-d-aspartate (NMDA) receptors under the other pathway, we made whole-cell recordings from LSO principal cells in acute slices of neonatal rat brainstem bathed in the use-dependent NMDA receptor antagonist MK-801 and stimulated in the two opposing pathways. We found that during the first postnatal week glutamate spillover occurs bidirectionally from both immature excitatory terminals and immature inhibitory terminals. We further found that a population of postsynaptic NMDA receptors is shared: glutamate released from either pathway can diffuse to and activate these receptors. We suggest that these shared receptors contain the GluN2B subunit and are located extrasynaptically.