Secondary Ion Mass Spectrometry Imaging Reveals Changes in the Lipid Structure of the Plasma Membranes of Hippocampal Neurons following Drugs Affecting Neuronal Activity

ACS Chem Neurosci. 2021 May 5;12(9):1542-1551. doi: 10.1021/acschemneuro.1c00031. Epub 2021 Apr 26.


The cellular functions of lipids in the neuronal plasma membranes have been increasingly acknowledged, particularly their association to neuronal processes and synaptic plasticity. However, the knowledge of their regulatory mechanisms in neuronal cells remains sparse. To address this, we investigated the lipid organization of the plasma membranes of hippocampal neurons in relation to neuronal activity using secondary ion mass spectrometry imaging. The neurons were treated with drugs, particularly tetrodotoxin (TTX) and bicuculline (BIC), to induce chronic activation and silencing. Distinct lipid organization was found in the plasma membrane of the cell body and the neurites. Moreover, significant alterations of the levels of the membrane lipids, especially ceramides, phosphatidylserines, phosphatidic acids, and triacylglycerols, were observed under the TTX and BIC treatments. We suggest that many types of membrane lipids are affected by, and may be involved in, the regulation of neuronal function.

Keywords: ToF-SIMS; lipids; mass spectrometry imaging; membranes; neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane
  • Hippocampus
  • Neurons
  • Pharmaceutical Preparations*
  • Spectrometry, Mass, Secondary Ion*


  • Pharmaceutical Preparations