Molecular composition of the human primary visual cortex profiled by multimodal mass spectrometry imaging

Abstract

The primary visual cortex (area V1) is an extensively studied part of the cerebral cortex with well-characterized connectivity, cellular and molecular architecture and functions (for recent reviews see Amunts and Zilles, Neuron 88:1086–1107, 2015; Casagrande and Xu, Parallel visual pathways: a comparative perspective. The visual neurosciences, MIT Press, Cambridge, pp 494–506, 2004). In humans, V1 is defined by heavily myelinated fibers arriving from the radiatio optica that form the Gennari stripe in cortical layer IV, which is further subdivided into laminae IVa, IVb, IVcα and IVcβ. Due to this unique laminar pattern, V1 represents an excellent region to test whether multimodal mass spectrometric imaging could reveal novel biomolecular markers for a functionally relevant parcellation of the human cerebral cortex. Here we analyzed histological sections of three post-mortem brains with matrix-assisted laser desorption/ionization mass spectrometry imaging and laser ablation inductively coupled plasma mass spectrometry imaging to investigate the distribution of lipids, proteins and metals in human V1. We identified 71 peptides of 13 different proteins by in situ tandem mass spectrometry, of which 5 proteins show a differential laminar distribution pattern revealing the border between V1 and V2. High-accuracy mass measurements identified 123 lipid species, including glycerolipids, glycerophospholipids and sphingolipids, of which at least 20 showed differential distribution within V1 and V2. Specific lipids labeled not only myelinated layer IVb, but also IVa and especially IVc in a layer-specific manner, but also and clearly separated V1 from V2. Elemental imaging further showed a specific accumulation of copper in layer IV. In conclusion, multimodal mass spectrometry imaging identified novel biomolecular and elemental markers with specific laminar and inter-areal differences. We conclude that mass spectrometry imaging provides a promising new approach toward multimodal, molecule-based cortical parcellation.Electronic supplementary materialThe online version of this article (10.1007/s00429-018-1660-y) contains supplementary material, which is available to authorized users.

Regions and Connections: Complementary Approaches to Characterize Brain Organization and Function

“…Dating back to the work of Brodmann (1909), many have mapped discrete regions of the brain and assigned them specific functions (Broca 1861; Scoville and Milner 1957). More recent results support the idea that the brain can be divided into regions based on structural or functional features (a map often referred to as a “parcellation”; e.g., Amunts and Zilles 2015; Bludau and others 2014; Cohen and others 2008; Glasser and others 2016; González de San Román and others 2018; Lorenz and others 2017; Shen and others 2013). Parcellations defined by connectivity patterns generally conform to task-activation maps and other neurobiological boundaries (Gordon and others 2016; Wig and others 2014), further evidence of regional homogeneity—and convergence—of structure and function.…”

Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology

“…These methods include proton induced X-ray emission (PIXE, Stüber et al. (2014) ) and lipid mass spectrometry ( González de San Román et al., 2018 ), which could provide quantification of myelin for each imaging pixel, for example by estimating myelin concentration from sulfur and phosphorus ( Stüber et al., 2014 ). With the exception of one study ( Stüber et al., 2014 ), these methods have not been used in the validation papers we reviewed, but may be used in future studies to provide complementary information to traditional histological techniques.…”

“…Myelin is a highly complex substrate, with the dry mass consisting of about 70% lipids and 30% proteins ( Gopalakrishnan, Awasthi, Belkaid, Jr, Liazoghli, Colman, Dhaunchak, 2013 , O’Brien, Sampson, 1965 ). Its composition can vary between tissue types ( González de San Román et al., 2018 ), species ( Gopalakrishnan et al., 2013 ) and in pathologies ( Wheeler et al., 2008 ), and therefore different visualization strategies may be useful for different scenarios.…”

Advances in High‐resolution Maldi Mass Spectrometry for Neurobiology

“…The MSI data is then able to guide the laser microdissection for microproteomics of extracts, resulting in comprehensive characterization of cancerous tissue (Dewez et al, 2019). Histology and MSI were also combined to profile peptides and lipids in the human primary visual cortex and visualize differential localization of the biomolecules within the visual cortexes (Gonzalez de San Roman et al, 2018). To further improve histology-guided MSI, a new tool has recently been developed to use histology from adjacent tissues to focus analysis on specific areas of interest, instead of relying on analysis of large areas of tissue (Heijs et al, 2015a).…”

“…While the presence of protein isoforms can greatly complicate MS spectra, the use of FTMS enables the ability to accurately identify these modified proteins as potential biomarkers. The analysis of these proteins was correlated with other biomolecules through a multimodal MSI approach involving laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI), a hard ionization technique (Gonzalez de San Roman et al, 2018). LA-ICP-MSI and MALDI-MSI was used to identify and elucidate the distributions of 13 proteins, 71 peptides, and 123 lipid species in human brain primary visual cortex tissue (Gonzalez de San Roman et al, 2018).…”