Exploring Brain Chemistry In Vivo Using LC-MS

Monitoring the chemical changes that occur in the extracellular space of the brain has generated important insights into brain function. Microdialysis sampled coupled to analytical methods is unique among methods available for studying brain chemistry in vivo because of its utility for providing multiplexed measurements. By analyzed fractions by both targeted and untargeted metabolomics style analysis, we have been able to achieve deep dives into brain chemistry. With untargeted methods, we have identified over 600 compounds in the brain extracellular space and demonstrated that about 70% of those can be monitored in routine experiments. These tools allow identification of a "chemical state" of the brain under different conditions. Using this method, we have identified chemical differences in behavioral phenotypes i.e., the brain chemistry that underlies behavioral differences. Further, we have examined how the brain metabolome changes with respect to exposure to cocaine. This talk will discuss the approaches used to achieve identification and monitoring based on LC-MS, database matching, and chemical derivatization. Further, we will highlight how the method has been used to find pathways altered by behavior and exposure to addictive substances.