High-Probability Neurotransmitter Release Sites Represent an Energy-Efficient Design.
Nerve terminals contain multiple sites specialized for the release of neurotransmitters. Release usually occurs with low probability, a design thought to confer many advantages. High-probability release sites are not uncommon, but their advantages are not well understood. Here, we test the hypothesis that high-probability release sites represent an energy-efficient design. We examined release site probabilities and energy efficiency at the terminals of two glutamatergic motor neurons synapsing on the same muscle fiber in Drosophila larvae. Through electrophysiological and ultrastructural measurements, we calculated release site probabilities to differ considerably between terminals (0.33 versus 0.11). We estimated the energy required to release and recycle glutamate from the same measurements. The energy required to remove calcium and sodium ions subsequent to nerve excitation was estimated through microfluorimetric and morphological measurements. We calculated energy efficiency as the number of glutamate molecules released per ATP molecule hydrolyzed, and high-probability release site terminals were found to be more efficient (0.13 versus 0.06). Our analytical model indicates that energy efficiency is optimal (∼0.15) at high release site probabilities (∼0.76). As limitations in energy supply constrain neural function, high-probability release sites might ameliorate such constraints by demanding less energy. Energy efficiency can be viewed as one aspect of nerve terminal function, in balance with others, because high-efficiency terminals depress significantly during episodic bursts of activity.
Integrative Biology and Neuroscience Graduate Program, Department of Biological Sciences and Wilkes Honors College, Florida Atlantic University, Jupiter, FL 33458, USA.
Zhongmin
Z
Lu
School of Psychology and Neuroscience, University of St Andrews, St Andrews KY16 9AJ, Scotland, UK.
Amit K
AK
Chouhan
Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Jolanta A
JA
Borycz
Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Zhiyuan
Z
Lu
Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Adam J
AJ
Rossano
Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Keith L
KL
Brain
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
You
Y
Zhou
Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Ian A
IA
Meinertzhagen
Department of Biological Sciences and Wilkes Honors College, Florida Atlantic University, Jupiter, FL 33458, USA. Electronic address: macleodg@fau.edu.
Gregory T
GT
Macleod
D000818:Animals; D004331:Drosophila melanogaster / Q000254:growth & development / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D007814:Larva / Q000254:growth & development / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D009435:Synaptic Transmission
D018698:Glutamic Acid
active zones; energy efficiency; evolutionary biology; neurotransmitter release; presynaptic; probability