In the postgenomic era, one expects the suite of chemical players in a brain region to be known and their functions uncovered. However, many cell-to-cell signaling molecules remain poorly characterized and for those that are known, their localization and dynamics are oftentimes unknown. A suite of bioanalytical / bioengineering approaches are described that allow the investigation of individual neurons and small brain regions; these approaches include capillary scale separations coupled to mass spectrometry and direct mass spectrometric-based profiling and imaging.
Several applications of single cell microanalysis are highlighted: investigating novel indolamine neurochemistry, determining the role of d-aspartate in the brain, and characterizing the peptides in single cells. Specifically, new serotonin-related compounds and literally hundreds of new neuropeptides have been characterized in well-defined neuronal networks, and in several cases, the functional roles of these molecules described. Imaging mass spectrometry and dynamic sampling of the extracellular environment are used for elucidating novel cell to cell signaling molecules in a range of neuronal model systems.
Current technology efforts involve extending the depth of metabolome coverage and adapting these analytical approaches to higher throughput single cell assays. Our overarching goal is to uncover the complex chemical mosaic of the brain and pinpoint key cellular players in physiological and pathological processes. Several additional examples of neuropeptide and neuromodulator discovery are described across a range of metazoan life.