Developmental mechanisms for suppressing the effects of delayed release at the endbulb of Held

J Neurosci. 2010 Aug 25;30(34):11466-75. doi: 10.1523/JNEUROSCI.2300-10.2010.


Delayed release of neurotransmitter, also called asynchronous release, is commonly observed at synapses, yet its influence on transmission of spike information is unknown. We examined this issue at endbulb of Held synapses, which are formed by auditory nerve fibers onto bushy cells in the cochlear nucleus. Endbulbs from CBA/CaJ mice aged P6-P49 showed prominent delayed release when driven at physiologically relevant rates. In bushy cells from mice before the onset of hearing (P6-P12), spikes were driven by delayed release up to 100 ms after presynaptic activity. However, no such spikes were observed in bushy cells from mice after the onset of hearing (>P14). Dynamic-clamp experiments indicated that delayed release can drive spikes in older bushy cells provided synchronous release is absent, suggesting that activity normally suppresses these spikes. Application of apamin or alpha-dendrotoxin revealed late spikes in older bushy cells, suggesting that postsynaptic activation of K(V)1.x and SK channels during spiking suppresses the subsequent effects of delayed release. The developmental upregulation of these potassium channels would be highly adaptive for temporally precise auditory processing. Furthermore, delayed release appeared to influence synchronous neurotransmitter release. Enhancement of delayed release using strontium was correlated with lower firing probability in current clamp and smaller synchronous EPSCs in voltage clamp. EGTA-AM had the opposite effects. These effects were consistent with delayed and synchronous release competing for a single vesicle pool. Thus delayed release apparently has negative presynaptic and postsynaptic consequences at the endbulb, which are partly mitigated by postsynaptic potassium channel expression.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Animals, Newborn
  • Cochlear Nucleus / growth & development*
  • Cochlear Nucleus / metabolism*
  • Excitatory Postsynaptic Potentials / physiology
  • Mice
  • Mice, Inbred CBA
  • Neurotransmitter Agents / metabolism
  • Reaction Time / physiology
  • Synapses / metabolism*
  • Synapses / physiology
  • Time Factors


  • Neurotransmitter Agents