Fig 2: Quantitative phase image of a live hippocampal neuron. Color bar indicates phase in radians (Popescu)

Brain and neural imaging has long been a core strength at the University of Illinois - for example, Paul Lauterbur won the Nobel Prize in Medicine or Physiology in 2003 for his development of functional magnetic resonance imaging (fMRI).  Liang, Hwu, Kamalabadi, and PI Jones employ novel data acquisition and image reconstruction algorithms in fMRI for more precise functional mapping of the brain.  One recent breakthrough, the first known “real-time fMRI” technique, exploits massive parallelization of the reconstruction algorithm and uses a parallel processor system. The event-related optical signal (EROS), a non-invasive optical measurement of neuronal activity with both sub-cm spatial and sub-msec temporal resolution, was pioneered at the U of I by Gratton and Fabiani.  With Clayton, EROS is being applied in the best animal model for learned vocal communication, the songbird. Popescu with Gillette recently applied a novel optical imaging technique, quantitative phase imaging (QPI) to quantify sub-nanometer motions associated with neuronal electric activity (Fig 2).  As large numbers of neurons can be followed simultaneously, QPI can potentially replace electrophysiology and voltage-sensitive dye imaging.  The prior imaging approaches are non-invasive but are limited in the number of distinct chemical species that can be characterized. The brain uses hundreds!  Thus, in addition, several chemically information-rich mass spectrometric imaging approaches are being developed that are well suited to examining ex vivo brain slices and cultured neuronal networks (see the next thrust).  Sweedler, Kelleher, and colleagues have been developing approaches for following cell-cell signaling with spatial and chemical information (Fig 3); when combined with peptidomic technologies for characterizing novel neuropeptides, unmatched information on the functional interactions between brain regions becomes available.  These approaches are being used with Gillette, Robinson, and Clayton to elucidate novel aspects of circadian biology, learning and the neural control of social behaviors.  A short outline of the research activities and associated faculty in this area is listed below:

Future Directions of This Thrust

Fig 3: Using mass spectrometry, unknown neuropeptides can be characterized along a single neuronal process (Sweedler) A major goal involves integration of the imaging modalities already under development with each other to provide tools that provide spatial, temporal, chemical and activity-related information from the brain.  Rather than list the individual projects, whether real-time functional brain imaging, imaging of neuronal activity, optical imaging, or chemical imaging, a key goal of the IGERT is to integrate these disparate approaches in the context of graduate education.  This is especially important from a training perspective, as these approaches have been developed under different research rubrics, from engineering, biophysics, chemistry and neuroscience, and the individuals do not always communicate across disciplinary jargons or interact as needed.  Our goal is to merge studies of physiology, metabolism (through fMRI), cell-cell signaling (through imaging mass spectrometry) with electrical activity to provide unmatched information and an exciting glimpse into the activity of neuronal circuits in well-defined models.  These efforts will be integrated with studies to understand how the brain changes during learning, and even under the influence of acute drug exposure (through our National Institutes on Drug Abuse’s Neuroproteomics Center on Cell-Cell Signaling,  A goal is to use the range of neuroscience models (such as the song bird, sea slug and rat) with the strengths of this imaging thrust to understand common aspects that occur during learning and the changes that occur during social behaviors.