Key physiological parameters dictate triggering of activity-dependent bulk endocytosis in hippocampal synapses

Eva M Wenzel, Andrew Morton, Katrin Ebert, Oliver Welzel, Johannes Kornhuber, Michael A Cousin, Teja W Groemer

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

To maintain neurotransmission in central neurons, several mechanisms are employed to retrieve synaptically exocytosed membrane. The two major modes of synaptic vesicle (SV) retrieval are clathrin-mediated endocytosis and activity-dependent bulk endocytosis (ADBE). ADBE is the dominant SV retrieval mode during intense stimulation, however the precise physiological conditions that trigger this mode are not resolved. To determine these parameters we manipulated rat hippocampal neurons using a wide spectrum of stimuli by varying both the pattern and duration of stimulation. Using live-cell fluorescence imaging and electron microscopy approaches, we established that stimulation frequency, rather than the stimulation load, was critical in the triggering of ADBE. Thus two hundred action potentials, when delivered at high frequency, were sufficient to induce near maximal bulk formation. Furthermore we observed a strong correlation between SV pool size and ability to perform ADBE. We also identified that inhibitory nerve terminals were more likely to utilize ADBE and had a larger SV recycling pool. Thus ADBE in hippocampal synaptic terminals is tightly coupled to stimulation frequency and is more likely to occur in terminals with large SV pools. These results implicate ADBE as a key modulator of both hippocampal neurotransmission and plasticity.
Original languageEnglish
Pages (from-to)e38188
JournalPLoS ONE
Volume7
Issue number6
DOIs
Publication statusPublished - 2012

Keywords

  • Action Potentials
  • Animals
  • Electric Stimulation
  • Endocytosis
  • Endosomes
  • Hippocampus
  • Presynaptic Terminals
  • Rats
  • Rats, Wistar
  • Reproducibility of Results
  • Synapses

Fingerprint

Dive into the research topics of 'Key physiological parameters dictate triggering of activity-dependent bulk endocytosis in hippocampal synapses'. Together they form a unique fingerprint.

Cite this