Elsevier

Neuroscience

Volume 196, 24 November 2011, Pages 285-296
Neuroscience

Regeneration, Repair, and Developmental Neuroscience
Research Paper
Glutamatergic inputs and glutamate-releasing immature inhibitory inputs activate a shared postsynaptic receptor population in lateral superior olive

https://doi.org/10.1016/j.neuroscience.2011.08.060Get rights and content

Abstract

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.

Highlights

▶The mature lateral superior olive receives glutamatergic and glycinergic inputs. ▶The immature glycinergic inputs also release glutamate. ▶We asked whether these pathways could engage in glutamatergic crosstalk. ▶Glutamate spillover can activate NMDA receptors shared by both pathways. ▶Shared NMDA receptors may be proximal to classic glutamatergic synapses.

Section snippets

Slice preparation

Sprague–Dawley rats born to animals bred on site or shipped pregnant (Charles River Laboratories, Wilmington, MA, USA) were used; all procedures were performed in accord with Canadian Council on Animal Care guidelines and were previously approved by the Animal Review Ethics Board of McMaster University. Rat pups aged P3–P8 were deeply anesthetized (isoflurane), and the brain was quickly removed and placed in ice-cold artificial cerebrospinal fluid (ACSF) containing (in mM): NaCl, 124; MgSO4, 1;

Glutamate spillover at room temperature

As glutamate release at MNTB–LSO synapses is most prevalent before P9, we focused on slices from animals age P3–P8. Little is known about the subcellular position of synapses in the immature LSO, and we asked whether synapses under the two pathways were sufficiently close to be within each other's glutamate diffusion radius at room temperature. To test for the possibility of spillover, we located LSO principal cells that showed a mixed GABA/glycine/glutamate response to MNTB stimulation (Fig. 1

Discussion

In rodent auditory brainstem, expression of VGLUT3 allows glutamate release from immature inhibitory terminals during the first postnatal week, and before P9 a majority of LSO principal neurons exhibit a glutamatergic response to stimulation of the MNTB pathway (Gillespie et al., 2005), as well of course to stimulation of the AVCN pathway (Ene et al., 2003). Investigating the possibility of glutamate spillover in the LSO, we found that stimulation of either pathway resulted in the activation of

Acknowledgments

This study was supported by infrastructure funds from the Canadian Foundation for Innovation, an operating grant from the Canadian Institutes for Health Research (D.C.G.), and a CONACyT postdoctoral fellowship (J.A.). The authors would like to thank Dan Case and Dan Goldreich for comments on the manuscript.

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