Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling

Catherine R. Wasser, Mert Ertunc, Xinran Liu, Ege T. Kavalali

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Cholesterol is a prominent component of nerve terminals. To examine cholesterol's role in central neurotransmission, we treated hippocampal cultures with methyl-β-cyclodextrin, which reversibly binds cholesterol, or mevastatin, an inhibitor of cholesterol biosynthesis, to deplete cholesterol. We also used hippocampal cultures from Niemann-Pick type C1-deficient mice defective in intracellular cholesterol trafficking. These conditions revealed an augmentation in spontaneous neurotransmission detected electrically and an increase in spontaneous vesicle endocytosis judged by horseradish peroxidase uptake after cholesterol depletion by methyl-β-cyclodextrin. In contrast, responses evoked by action potentials and hypertonicity were severely impaired after the same treatments. The increase in spontaneous vesicle recycling and the decrease in evoked neurotransmission were reversible upon cholesterol addition. Cholesterol removal did not impact on the low level of evoked neurotransmission seen in the absence of synaptic vesicle SNARE protein synaptobrevin-2 whereas the increase in spontaneous fusion remained. These results suggest that synaptic cholesterol balances evoked and spontaneous neurotransmission by hindering spontaneous synaptic vesicle turnover and sustaining evoked exo-endocytosis.

Original languageEnglish (US)
Pages (from-to)413-429
Number of pages17
JournalJournal of Physiology
Volume579
Issue number2
DOIs
StatePublished - Mar 1 2007

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Synaptic Vesicles
Cholesterol
Synaptic Transmission
Cyclodextrins
Endocytosis
Vesicle-Associated Membrane Protein 2
Anticholesteremic Agents
SNARE Proteins
Recycling
Horseradish Peroxidase
Evoked Potentials
Action Potentials

ASJC Scopus subject areas

  • Physiology

Cite this

Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling. / Wasser, Catherine R.; Ertunc, Mert; Liu, Xinran; Kavalali, Ege T.

In: Journal of Physiology, Vol. 579, No. 2, 01.03.2007, p. 413-429.

Research output: Contribution to journalArticle

Wasser, Catherine R. ; Ertunc, Mert ; Liu, Xinran ; Kavalali, Ege T. / Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling. In: Journal of Physiology. 2007 ; Vol. 579, No. 2. pp. 413-429.
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