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

Area of Science:

• Neuroscience
• Biochemistry
• Analytical Chemistry

Background:

• The primary visual cortex (V1) is well-characterized but its molecular architecture remains incompletely understood.
• V1's unique laminar structure, including the Gennari stripe, makes it ideal for molecular mapping.
• Novel methods are needed to identify molecular markers for functional cortical parcellation.

Purpose of the Study:

• To investigate the distribution of lipids, proteins, and metals in human V1 using multimodal mass spectrometry imaging.
• To identify novel biomolecular and elemental markers for laminar and inter-areal differences within the visual cortex.
• To assess the potential of mass spectrometry imaging for molecule-based cortical parcellation.

Main Methods:

• Histological sections from three post-mortem human brains were analyzed.
• Matrix-assisted laser desorption/ionization mass spectrometry imaging and laser ablation inductively coupled plasma mass spectrometry imaging were employed.
• In situ tandem mass spectrometry and high-accuracy mass measurements were used for peptide and lipid identification.

Main Results:

• 71 peptides from 13 proteins were identified, with 5 showing differential laminar distribution, demarcating V1/V2 borders.
• 123 lipid species were identified, with over 20 exhibiting differential distribution, including specific lipids labeling distinct layers (IVa, IVb, IVc).
• Elemental imaging revealed specific copper accumulation in layer IV, and lipids clearly separated V1 from V2.

Conclusions:

• Multimodal mass spectrometry imaging successfully identified novel biomolecular and elemental markers in human V1.
• These markers exhibit specific laminar and inter-areal distribution patterns.
• Mass spectrometry imaging presents a promising new avenue for molecule-based, multimodal cortical parcellation.