Waitt Advanced Biophotonics Center
The human brain consists of sets of cells that form networks of dazzling complexity. Much research has focused on understanding the circuits formed by neurons, the electrically-excitable cells that process and transmit information. However, glial cells, the second major cell type in the brain, account for about ninety percent of human brain cells and more than fifty percent of the brain's volume. For a long time, these cells were believed to have a merely passive, supportive role. However, over the past few years, it has become clear that glial cells make crucial contributions to the formation, operation and adaptation of neural circuitry.
Work in my lab is centered on innovating light microscopic tools that enable the study of these electrically largely non-excitable cells and their interaction with other cells in the intact mammalian brain. We have created tools for cell-type-specific staining and genetic manipulation, for imaging cellular dynamics in awake behaving mammals and for automated analysis of large-scale imaging data. This allows us to directly address longstanding questions regarding glial function in the intact healthy and diseased brain. Resolving these fundamental questions has broad implications for our view of glial cells, the way information is processed in the brain, the interpretation of functional brain imaging signals and the treatment of neurodegenerative brain disease.
"My lab studies an enigmatic set of cells called glia, which are involved in many nervous system injuries and diseases. Most treatment efforts have focused on neurons, but determining how glial cells function normally and become dysfunctional in disease is critical for development of new and improved treatments for such disorders."
The human brain consists of an incredibly diverse set of cells, and each cell type fulfills highly specialized functions in cellular networks of dazzling complexity. While much research has focused on understanding the circuits formed by neurons, glial cells account for up to 90 percent of cells in the human brain and around half of its volume. These cells were long believed to play a merely passive, supportive role. However, over the past few years it has become clear that glia make crucial contributions to the formation, operation and adaptation of the nervous system. Additionally, glial cells are involved in many injuries and diseases, including cancer, Alexander's disease and amyotrophic lateral sclerosis.
Work in Nimmerjahn's laboratory centers on developing microscopic tools that enable the study of glial cells and their interaction with other cells in the normal and diseased brain. He and his team have developed tools for staining and genetically manipulating specific cell types, imaging cellular dynamics in the brain and automating analysis of largescale imaging data. Using these tools, they showed, for example, that "resting" microglia— the resident immune cells within our brain—have highly mobile branches that provide extensive and continuous surveillance of intercellular spaces, and that upon local disruption of the blood-brain barrier, microglia rapidly shield the site of injury and clear cellular debris. Using custom miniature fluorescence microscopes, Nimmerjahn's team provided the first optical measurement of neuronal and glial activity during behavior. This allowed them to reveal unknown forms of neuronal and astroglial excitation and to determine how these dynamic patterns are altered by behavior and anesthesia.
Nimmerjahn's laboratory currently focuses on the development of new, integrated tools for study of glia–neuron and glia–vascular interactions in superficial and deep regions of the healthy and diseased brain. This work promises to yield better understanding of glial cells' role in information processing, regulation of vascular dynamics, and brain disorders that either result from, or are exacerbated by, defective or disordered glial function, such as migraine, stroke or cancer.
From left to right: Yusuf Tufail, Pavel Shekhtmeyster, Christopher Aprea, Axel Nimmerjahn, Charles Clark, Da Meng
Knowland, D., Arac, A., Sekiguchi, K.J., Hsu, M., Lutz, S.E., Perrino, J., Steinberg, G.K., Barres, B.A., Nimmerjahn, A.*, and Agalliu, D.* (2014). Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier breakdown in stroke. Neuron, in press. *Authors contributed equally [Link to article]
Ghosh, K.K., Burns, L.D., Cocker, E.D., Nimmerjahn, A., Ziv, Y., Gamal, A.E., and Schnitzer, M.J. (2011). Miniaturized integration of a fluorescence microscope. Nature Methods 8, 871-878.
Nimmerjahn, A., Mukamel, E.A., and Schnitzer, M.J. (2009). Motor behavior activates Bergmann glial networks. Neuron 62, 400-412.
Mukamel, E.A., Nimmerjahn, A., and Schnitzer, M.J. (2009). Automated analysis of cellular signals from large-scale calcium-imaging data. Neuron 63, 747-760.
Flusberg, B.A.*, Nimmerjahn, A.*, Cocker, E.D.*, Mukamel, E.A., Barretto, R.P.J., Ko, T.H., Burns, L.D., Jung, J.C., and Schnitzer, M.J. (2008). High-speed, miniaturized fluorescence microscopy in freely moving mice. Nature Methods 5, 935-938. *Authors contributed equally
Nimmerjahn, A., Kirchhoff, F., and Helmchen, F. (2005). Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314-1318.
Nimmerjahn, A., Kirchhoff, F., Kerr, J.N.D., and Helmchen, F. (2004). Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo. Nature Methods 1, 31-37.
Dittgen, T., Nimmerjahn, A., Komai, S., Licznerski, P., Waters, J., Margrie, T.W., Helmchen, F., Denk, W., Brecht, M., and Osten, P. (2004). Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo. Proc. Natl. Acad. Sci. USA 101, 18206-18211.
For a complete listing of publications on PubMed, click here>>
Salk News Releases
Scientists identify new cause of brain bleeding immediately after stroke
April 17, 2014
Innovative research earns Salk scientist EUREKA award
October 11, 2013
A rare feat: Two scientists at Salk score NIH New Innovator awards
September 13, 2012
Salk scientist earns competitive grant from Whitehall Foundation
September 21, 2011
Salk scientist named Rita Allen Scholar
June 22, 2011
Salk Institute celebrates Grand Opening of the Waitt Advanced Biophotonics Center
February 9, 2011
Awards and Honors
- National Institutes of Health (NIH) Exceptional Unconventional Research Enabling Knowledge Acceleration (EUREKA) Award, 2013-2017
- National Institutes of Health (NIH) Director's New Innovator Award, 2012-2017
- Whitehall Foundation Award, 2011-2014
- Rita Allen Scholar Award, 2011-2016
- Human Frontiers Science Program (HFSP) Postdoctoral Fellowship, 2006-2009
- Feodor Lynen Research Fellowship of the Alexander von Humboldt Foundation, 2006
- Otto-Hahn-Medal and -Award of the Max Planck Society, 2006
- Du Bois-Reymond Award of the German Physiologic Society, 2006
- Böhringer Ingelheim Fonds (B.I.F.) Predoctoral Fellowship, 2002-2005