Mass spectrometric imaging of the nervous system.

Mass spectrometric imaging (MSI) integrates multiple fields of analytical and biomedical research with the goal of generating chemical maps that present the identity and location of the elements, molecules, and molecular complexes that comprise biological structures. Rapid advances in the development of MSI, which include a broad range of sampling and mass spectrometry strategies, allow the increasingly information-rich creation of chemical images of structurally complex tissues, individual cells, and even single chromosomes. Here we describe a variety of MSI techniques available to investigate the nervous system, with particular focus on the capability of MSI to examine both normal and diseased brain function. An important investigative tool, MSI offers tremendous potential in fundamental studies of brain chemistry, localization of pharmaceutical compounds, and the discovery of biomarkers for different neuropathologies.

Phasic dopamine signaling during behavior, reward, and disease states.

The neurotransmitter dopamine is important in reward processing, however its precise modulatory role is still being investigated. Carbon-fiber microelectrodes can be used to monitor dopamine on a subsecond time scale in the striatum and nucleus accumbens of rats during behavior, and this approach is providing new insights into the mechanisms that control its extracellular concentration as well as the conditions under which it is released. Three main processes govern the amount of dopamine measured extrasynaptically: exocytotic release, neuronal uptake, and diffusion away from the release site. By monitoring local extracellular dopamine concentrations in the striatum following electrical stimulation of dopamine-containing neurons, release, uptake and diffusion can be individually examined and quantified. Dopaminergic neurons have been shown to fire in two firing modes, tonic and bursts at higher frequency. Electrical stimulation can be designed to mimic either mode to examine their effects on dopamine release. Burst firing causes a transient increase in extracellular dopamine while tonic firing causes a new steady-state level. In behaving primates, dopaminergic neurons display short-latency, phasic firing to primary reward and conditioned cues associated with reward. These bursts code differences between actual and predicted rewards. In rats, transient dopamine release in terminal regions that mimics that seen during burst firing has been demonstrated during reward-related cues. Taken together, these studies indicate that phasic dopamine release is a critical mediator of reward-related processes.