High probability neurotransmitter release sites represent an energy efficient design

Research output: Contribution to journalArticle


  • Lu Zhongmin
  • Amit K. Chouhan
  • Adam J Rossano
  • You Zhou
  • Jolanta A. Borycz
  • Zhiyaun Lu
  • Ian A. Meinertzhagen
  • Gregory T. Macleod

Colleges, School and Institutes

External organisations

  • Department of Biological Sciences; Florida Atlantic University; Davie; Florida; USA
  • Univ St Andrews
  • Department of Health Sciences Research, Mayo Clinic
  • University of Texas Health Science Center, San Antonio, TX, USA.
  • Department of Psychology and Neuroscience, Dalhousie University, Halifax, Nova Scotia


At most synapses, the probability of neurotransmitter release from an active zone (PAZ) is low, a design thought to confer many advantages. Yet, high PAZ can also be found at synapses. Speculating that high PAZ confers high energy efficiency, we examined energy efficiency at terminals of two Drosophila motor neurons (MNs) synapsing on the same muscle fiber, but with contrasting average PAZ. Through electrophysiological and ultrastructural measurements we calculated average PAZ for MNSNb/d-Is and MN6-Ib terminals (0.33±0.10 and 0.11±0.02 respectively). Using a miles-per-gallon analogy, we calculated efficiency as the number of glutamate molecules released for each ATP molecule that powers the release and recycling of glutamate and the removal of calcium (Ca2+) and sodium (Na+). Ca2+ and Na+ entry were calculated by microfluorimetry and morphological measurements respectively. Terminals with the highest PAZ release more glutamate but admit less Ca2+ and Na+, supporting the hypothesis that high PAZ confers greater energy efficiency than low PAZ (0.13±0.02 and 0.06±0.01 respectively). In an analytical treatment of parameters that influence efficiency we found that efficiency could be optimized in either terminal by increasing PAZ. Terminals with highest PAZ operate closest to this optimum but are less active and less able to sustain high release rates. Adopting an evolutionary biological perspective, we interpret the persistence of low PAZ release sites at more active terminals to be the result of selection pressures for sustainable neurotransmitter release dominating selection pressures for high energy efficiency.


Original languageEnglish
Pages (from-to)2562-2571
Number of pages10
JournalCurrent Biology
Issue number19
Early online date1 Sep 2016
Publication statusPublished - 10 Oct 2016

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