Our aim is to investigate the function of the living brain using multiphoton microscopy in combination with other techniques. We visualize the structure and function of nervous tissue under physiological and pathophysiological conditions with the ultimate goal of studying human disease models. We investigate neural cells on the dissociated cell level (e.g., primary neuronal culture), the tissue explant level (e.g. acute brain slices), and at the true in-vivo level (e.g. imaging through cranial windows in living rodents).

Multiphoton fluorescence microscopy and second-harmonic-microscopy may provide the most advanced available imaging techniques for investigating cellular processes in turbid tissues with minimal perturbation of the delicate machinery of the cell.

One major focus is the use of intrinsic signals (e.g. the electron donor NADH) as metabolic and disease indicators. Obvious advantages are that native, unstained tissue can be investigated "as is" and that the signal originates directly from the intracellular molecule of interest. Challenges we are working on are imaging these relatively weak intrinsic signals deep in scattering brain tissue and considering their complex interactions with the intracellular environment.

Reference: Kasischke, K. A., H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel and W. W. Webb, "Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis," Science 305(5680), 99-103, 2004 [Follow-up Letter: Kasischke, K. A. and W. W. Webb, “Producing Neuronal Energy - Response,” Science 306(5695), 410-411, 2004]

The links below introduce various aspects of our research.

Fundamental Aspects                                             Biological Applications

NADH - an intrinsically fluorescent molecule that provides a measure of cellular metabolic states

Functional Imaging: Visualizing energy metabolism in the CNS with microscopic resolution

We would also like to acknowledge our collaborators:

Bradley T. Hyman, M.D., Ph.D., Dept. of Neurology, Massachusetts General Hospital, Boston, MA

Abraham Brown Ph.D., Dept. of Biochemistry,Weill Medical College of Cornell University, White Plains, NY

Additionally, we recommend that you look at the Alzheimer Research Forum website for up-to-the-minute news on Alzheimer's Disease research.