Fast, Temperature-Sensitive and Clathrin-Independent Endocytosis at Central Synapses

Neuron. 2016 May 4;90(3):492-8. doi: 10.1016/j.neuron.2016.03.013. Epub 2016 Apr 14.

Abstract

The fusion of neurotransmitter-filled vesicles during synaptic transmission is balanced by endocytotic membrane retrieval. Despite extensive research, the speed and mechanisms of synaptic vesicle endocytosis have remained controversial. Here, we establish low-noise time-resolved membrane capacitance measurements that allow monitoring changes in surface membrane area elicited by single action potentials and stronger stimuli with high-temporal resolution at physiological temperature in individual bona-fide mature central synapses. We show that single action potentials trigger very rapid endocytosis, retrieving presynaptic membrane with a time constant of 470 ms. This fast endocytosis is independent of clathrin but mediated by dynamin and actin. In contrast, stronger stimuli evoke a slower mode of endocytosis that is clathrin, dynamin, and actin dependent. Furthermore, the speed of endocytosis is highly temperature dependent with a Q10 of ∼3.5. These results demonstrate that distinct molecular modes of endocytosis with markedly different kinetics operate at central synapses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Clathrin / metabolism*
  • Endocytosis / physiology*
  • Estriol / analogs & derivatives*
  • Estriol / physiology
  • Hippocampus / metabolism
  • Mice, Inbred C57BL
  • Rats
  • Synaptic Transmission / physiology
  • Temperature
  • Time Factors

Substances

  • Clathrin
  • estriol succinate
  • Estriol