Leaky synapses: Regulation of spontaneous neurotransmission in central synapses

C. R. Wasser, E. T. Kavalali

Research output: Contribution to journalReview article

38 Scopus citations

Abstract

The mechanisms underlying spontaneous neurotransmitter release are not well understood. Under physiological as well as pathophysiological circumstances, spontaneous fusion events can set the concentration of ambient levels of neurotransmitter within the synaptic cleft and in the extracellular milieu. In the brain, unregulated release of excitatory neurotransmitters, exacerbated during pathological conditions such as stroke, can lead to neuronal damage and death. In addition, recent findings suggest that under physiological circumstances spontaneous release events can trigger postsynaptic signaling events independent of evoked neurotransmitter release. Therefore, elucidation of mechanisms underlying spontaneous neurotransmission may help us better understand the functional significance of this form of release and provide tools for its selective manipulation. For instance, our recent investigations indicate that the level of cholesterol in the synapse plays a critical role in limiting spontaneous synaptic vesicle fusion. Therefore, alterations in synaptic cholesterol metabolism can be a critical determinant of glutamatergic neurotransmission at rest. This article aims to provide a closer look into our current understanding of the mechanisms underlying spontaneous neurotransmission and the signaling triggered by these unitary release events.

Original languageEnglish (US)
Pages (from-to)177-188
Number of pages12
JournalNeuroscience
Volume158
Issue number1
DOIs
StatePublished - Jan 12 2009

Keywords

  • SNARE
  • cholesterol
  • miniature synaptic transmission
  • spontaneous neurotransmission
  • synaptic vesicle recycling
  • synaptotagmin

ASJC Scopus subject areas

  • Neuroscience(all)

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