Prolonged reciprocal signaling via NMDA and GABA receptors at a retinal ribbon synapse

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48 Scopus citations


AMPA and GABAA receptors mediate most of the fast signaling in the CNS. However, the retina must, in addition, also convey slow and sustained signals. Given that AMPA and GABAA receptors desensitize quickly in the continuous presence of agonist, how are sustained excitatory and inhibitory signals transmitted reliably across retinal synapses? Reciprocal synapses between bipolar and amacrine cells in the retina are thought to play a fundamental role in tuning the bipolar cell output to the dynamic range of ganglion cells. Here, we report that glutamate release from goldfish bipolar cell terminals activates first AMPA receptors, followed by fast and transient GABAA-mediated feedback. Subsequently, prolonged NMDA receptor activation triggers GABAA and a slow, sustained GABA C-mediated reciprocal inhibition. The synaptic delay of the NMDA/GABAC-mediated feedback showed stronger dependence on the depolarization of the bipolar cell terminal than the fast AMPA/GABA A-mediated response. Although the initial depolarization mediated by AMPA receptors was important to prime the NMDA action, NMDA receptors could trigger feedback by themselves in most of the bipolar terminals tested. This AMPA-independent feedback (delay ≈ 10 ms) was eliminated in 2 mM external Mg2+ and reduced in some terminals, but not eliminated, by TTX. NMDA receptors on amacrine cells with depolarized resting membrane potentials therefore can mediate the late reciprocal feedback triggered by continuous glutamate release. Our findings suggest that the characteristics of NMDA receptors (high agonist affinity, slow desensitization, and activation/ deactivation kinetics) are well suited to match the properties of GABA C receptors, which thus provide part of the prolonged inhibition to bipolar cell terminals.

Original languageEnglish (US)
Pages (from-to)11412-11423
Number of pages12
JournalJournal of Neuroscience
Issue number49
StatePublished - Dec 7 2005


  • AMPA receptor
  • Amacrine cells
  • GABA receptor
  • GABA receptor
  • NMDA receptor
  • Neurotransmission
  • Retinal bipolar cell

ASJC Scopus subject areas

  • Neuroscience(all)


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