Comprehensive mapping of neurotransmitter networks by MALDI-MS imaging

Nat Methods. 2019 Oct;16(10):1021-1028. doi: 10.1038/s41592-019-0551-3. Epub 2019 Sep 23.


We present a mass spectrometry imaging (MSI) approach for the comprehensive mapping of neurotransmitter networks in specific brain regions. Our fluoromethylpyridinium-based reactive matrices facilitate the covalent charge-tagging of molecules containing phenolic hydroxyl and/or primary or secondary amine groups, including dopaminergic and serotonergic neurotransmitters and their associated metabolites. These matrices improved the matrix-assisted laser desorption/ionization (MALDI)-MSI detection limit toward low-abundance neurotransmitters and facilitated the simultaneous imaging of neurotransmitters in fine structures of the brain at a lateral resolution of 10 µm. We demonstrate strategies for the identification of unknown molecular species using the innate chemoselectivity of the reactive matrices and the unique isotopic pattern of a brominated reactive matrix. We illustrate the capabilities of the developed method on Parkinsonian brain samples from human post-mortem tissue and animal models. The direct imaging of neurotransmitter systems provides a method for exploring how various neurological diseases affect specific brain regions through neurotransmitter modulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Disease Models, Animal
  • Humans
  • Limit of Detection
  • Neurotransmitter Agents / metabolism*
  • Parkinson Disease / metabolism
  • Primates
  • Rats
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*


  • Neurotransmitter Agents