Single Cell Neurometabolomics

Metabolomics, the characterization of metabolites and their changes within biological systems, has seen great technological and methodological progress over the past decade. Most metabolomic experiments involve the characterization of the small-molecule content of fluids or tissue homogenates. While these microliter and larger volume metabolomic measurements can characterize hundreds to thousands of compounds, the coverage of molecular content decreases as sample sizes are reduced to the nanoliter and even to the picoliter volume range. Recent progress has enabled the ability to characterize the major molecules found within specific individual cells. Especially within the brain, a myriad of cell types are colocalized, and oftentimes only a subset of these cells undergo changes in both healthy and pathological states. Here we highlight recent progress in mass spectrometry-based approaches used for single cell metabolomics, emphasizing their application to neuroscience research. Single cell studies can be directed to measuring differences between members of populations of similar cells (e.g., oligodendrocytes), as well as characterizing differences between cell types (e.g., neurons and astrocytes), and are especially useful for measuring changes occurring during different behavior states, exposure to diets and drugs, neuronal activity, and disease. When combined with other omics approaches such as transcriptomics, and with morphological and physiological measurements, single cell metabolomics aids fundamental neurochemical studies, has great potential in pharmaceutical development, and should improve the diagnosis and treatment of brain diseases.