Minimizing synaptic depression by control of release probability

Stephan Brenowitz, Laurence O. Trussell

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Transmission at the end-bulb synapse formed by auditory nerve terminals onto the soma of neurons in the avian nucleus magnocellularis is characterized by high transmitter release probability and strong synaptic depression. Activation of presynaptic GABAB receptors minimizes depression at this synapse and significantly enhances synaptic strength during high-frequency activity. Here we investigate synaptic mechanisms underlying this phenomenon. EPSC amplitudes evoked by 200 Hz trains increased more than twofold when release probability was reduced with Cd2+ or baclofen. This effect was not exhibited by a transmitter depletion model of presynaptic depression, which predicts that EPSC amplitudes reach a common steady-state amplitude during high-frequency trains, despite alterations of initial release probability. However, an additional source of postsynaptic depression was sufficient to explain our findings. Aniracetam, a modulator of AMPA receptors that reduces desensitization, decreased the amount of synaptic depression during trains, indicating that desensitization occurred during trains of stimuli. However, this effect of aniracetam was absent when release probability was lowered with baclofen or Cd2+. No effect of aniracetam on the NMDA component of the EPSC was seen, confirming a postsynaptic site of action of aniracetam. When desensitization was reduced with aniracetam, steady-state EPSC amplitudes during trains were found to converge over a wide range of release probabilities, as predicted by the depletion model. Additional evidence of AMPA receptor desensitization was provided by direct measurement of quantal amplitudes immediately after stimulus trains. Thus, presynaptic modulation by GABAB receptors regulates the extent of AMPA receptor desensitization and controls synaptic strength, thereby modulating the flow of information at an auditory synapse.

Original languageEnglish (US)
Pages (from-to)1857-1867
Number of pages11
JournalJournal of Neuroscience
Volume21
Issue number6
DOIs
StatePublished - Mar 15 2001

Keywords

  • AMPA receptors
  • Auditory
  • Cochlear nuc1eus
  • Desensitization
  • End-bulb synapse
  • GABA receptors
  • Short-term depression

ASJC Scopus subject areas

  • Neuroscience(all)

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