The Chromatography Forum

of Delaware Valley

Central to advancing neuroscience is characterizing and monitoring the chemical composition of the brain extracellular space. Neurotransmitters, neuromodulators, and other metabolites within this microenvironment reflect several physiological functions occurring simultaneously on different spatiotemporal scales. Elucidating the role that these metabolites play in normal and diseased brains can improve our understanding of neurological disorders, thereby providing potential new drug targets and therapies. This seminar will demonstrate how analytical advances in liquid chromatography-tandem mass spectrometry and untargeted chemometrics can enable a deeper annotation of the living brain metabolome. Using in vivo microdialysis sampling, we can routinely monitor hundreds of compounds present in the brain metabolome. These compounds not only represent a wide range of chemical functionalities but also exhibit diverse biological functions. Leveraging this sampling framework, we define baseline and cocaine-induced differences in neurochemistry between two behavioral phenotypes in a rodent model of addiction. These differences were found to be associated with several metabolic pathways such as stress, neuroinflammation, energy usage, and neurotransmission. Ultimately, these findings broaden our understanding of addiction’s impact on the brain and serve as the basis for ongoing efforts to better characterize neurochemical adaptations.