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Slow glycinergic transmission mediated by transmitter pooling

Nature Neuroscience volume 12, pages 286–294 (2009)Cite this article

Abstract

Most fast-acting neurotransmitters are rapidly cleared from synaptic regions. This feature isolates synaptic sites, rendering the time course of synaptic responses independent of the number of active synapses. We found an exception at glycinergic synapses on granule cells of the rat dorsal cochlear nucleus. Here the duration of inhibitory postsynaptic currents (IPSCs) was dependent on the number of presynaptic axons that were stimulated and on the number of vesicles that were released from each axon. Increasing the stimulus number or frequency, or blocking glycine uptake, slowed synaptic decays, whereas a low-affinity competitive antagonist of glycine receptors (GlyRs) accelerated IPSC decay. These effects could be explained by unique features of GlyRs that are activated by pooling of glycine across synapses. Functionally, increasing the number of IPSPs markedly lengthened the period of spike inhibition following the cessation of presynaptic stimulation. Thus, temporal properties of inhibition can be controlled by activity levels in multiple presynaptic cells or by adjusting release probability at individual synapses.

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Figure 1: Granule cells in the DCN and their glycinergic postsynaptic currents.
Figure 2: Asynchronous release.
Figure 3: Increasing release probability slows IPSC decay time.
Figure 4: Probing multivesicular release and receptor saturation using a weak antagonist of GlyRs, SR-95531.
Figure 5: SR-95531 accelerates the decay of IPSCs.
Figure 6: Simulation of IPSCs.
Figure 7: Contribution of IPSC decay time to the duration of inhibition.
Figure 8: Glycinergic nerve terminal density is consistent with spillover-mediated transmission.

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Acknowledgements

We thank H. Huang, C.E. Jahr and M.E. Roberts for comments on the manuscript and H. Sundaram for the gift of ORG-25543. This work was supported by US National Institutes of Health grant NS028901.

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Authors and Affiliations

  1. Oregon Hearing Research Center, 3181 S.W. Sam Jackson Park Road, Portland, 97239, Oregon, USA

    Veeramuthu Balakrishnan, Sidney P Kuo & Laurence O Trussell

  2. Vollum Institute, 3181 S.W. Sam Jackson Park Road, Portland, 97239, Oregon, USA

    Veeramuthu Balakrishnan, Sidney P Kuo & Laurence O Trussell

  3. Biomedical Engineering, 3181 S.W. Sam Jackson Park Road, Portland, 97239, Oregon, USA

    Patrick D Roberts

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  1. Veeramuthu Balakrishnan
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Contributions

V.B. conducted the electrophysiological experiments, analysis and manuscript preparation. S.P.K. performed immunohistochemistry and analysis. P.D.R. conducted diffusion modeling. L.O.T. conducted kinetic modeling, data analysis and wrote the manuscript.

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Correspondence to Laurence O Trussell.

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Balakrishnan, V., Kuo, S., Roberts, P. et al. Slow glycinergic transmission mediated by transmitter pooling. Nat Neurosci 12, 286–294 (2009). https://doi.org/10.1038/nn.2265

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