Axel Nimmerjahn

Research
Publications

Research

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 up to 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.

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Huang, Y., Happonen, K.E., Burrola, P.G., O'Connor, C., Hah, N., Huang, L., Nimmerjahn, A., Lemke, G. Microglia use TAM receptors to detect and engulf amyloid β plaques. (2021) Nature Immunology. DOI: 10.1038/s41590-021-00913-5
Ceto, S., Sekiguchi, K.J., Takashima, Y., Nimmerjahn, A., Tuszynski, M.H. Neural Stem Cell Grafts Form Extensive Synaptic Networks that Integrate with Host Circuits after Spinal Cord Injury. (2020) Cell Stem Cell. DOI: 10.1016/j.stem.2020.07.007
Nimmerjahn, A. Monitoring neuronal health. (2020) Science. 367(6477):510-511. DOI: 10.1126/science.aba4472
Patriarchi, T., Cho, J.R., Merten, K., Marley, A., Broussard, G.J., Liang, R., Williams, J., Nimmerjahn, A., von Zastrow, M., Gradinaru, V., Tian, L. Imaging neuromodulators with high spatiotemporal resolution using genetically encoded indicators. (2019) Nature Protocols. 14(12):3471–3505. DOI: 10.1038/s41596-019-0239-2
Nelson, N.A., Wang, X., Cook, D., Carey, E.M., Nimmerjahn, A. Imaging spinal cord activity in behaving animals. (2019) Experimental Neurology. 230:112974. DOI: 10.1016/j.expneurol.2019.112974
Patriarchi, T., Cho, J.R., Merten, K., Howe, M.W., Marley, A., Xiong, W.H., Folk, R.W., Broussard, G.J., Liang, R., Jang, M.J., Zhong, H., Dombeck, D., von Zastrow, M., Nimmerjahn, A., Gradinaru, V., Williams, J.T., Tian, L. Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. (2018) Science. DOI: 10.1126/science.aat4422
Tufail, Y., Cook, D., Fourgeaud, L., Powers, C.J., Merten, K., Clark, C.L., Hoffman, E., Ngo, A., Sekiguchi, K.J., O'Shea, C.C., Lemke, G., Nimmerjahn, A. Phosphatidylserine Exposure Controls Viral Innate Immune Responses by Microglia. (2017) Neuron. 93(3):574-586.e8. DOI: 10.1016/j.neuron.2016.12.021
Sekiguchi, K.J., Shekhtmeyster, P., Merten, K., Arena, A., Cook, D., Hoffman, E., Ngo, A., Nimmerjahn, A. Imaging large-scale cellular activity in spinal cord of freely behaving mice. (2016) Nature Communications. 7:11450. DOI: 10.1038/ncomms11450
Fourgeaud, L., Través, P.G., Tufail, Y., Leal-Bailey, H., Lew, E.D., Burrola, P.G., Callaway, P., Zagórska, A., Rothlin, C.V., Nimmerjahn, A., Lemke, G. TAM receptors regulate multiple features of microglial physiology. (2016) Nature. 532(7598):240-244. DOI: 10.1038/nature17630
Nimmerjahn, A., Bergles, D.E. Large-scale recording of astrocyte activity. (2015) Current Opinion in Neurobiology. 32:95-106. DOI: 10.1016/j.conb.2015.01.015
Knowland, D., Arac, A., Sekiguchi, K.J., Hsu, M., Lutz, S.E., Perrino, J., Steinberg, G.K., Barres, B.A., Nimmerjahn, A., Agalliu, D. Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier breakdown in stroke. (2014) Neuron. 82(3):603-17. DOI: 10.1016/j.neuron.2014.03.003
Devor, A., Bandettini, P.A., Boas, D.A., Bower, J.M., Buxton, R.B., Cohen, L.B., Dale, A.M., Einevoll, G.T., Fox, P.T., Franceschini, M.A., Friston, K.J., Fujimoto, J.G., Geyer, M.A., Greenberg, J.H., Halgren, E., Hämäläinen, M.S., Helmchen, F., Hyman, B.T., Jasanoff, A., Jernigan, T.L., Judd, L.L., Kim, S.G., Kleinfeld, D., Kopell, N.J., Kutas, M., Kwong, K.K., Larkum, M.E., Lo, E.H., Magistretti, P.J., Mandeville, J.B., Masliah, E., Mitra, P.P., Mobley, W.C., Moskowitz, M.A., Nimmerjahn, A., Reynolds, J.H., Rosen, B.R., Salzberg, B.M., Schaffer, C.B., Silva, G.A., So, P.T., Spitzer, N.C., Tootell, R.B., Van Essen, D.C., Vanduffel, W., Vinogradov, S.A., Wald, L.L., Wang, L.V., Weber, B., Yodh, A.G. The challenge of connecting the dots in the B.R.A.I.N. (2013) Neuron. 80(2):270-4. DOI: 10.1016/j.neuron.2013.09.008
Nimmerjahn, A. Two-photon imaging of microglia in the mouse cortex in vivo. (2012) Cold Spring Harbor Protocols. 2012(5). DOI: 10.1101/pdb.prot069294
Nimmerjahn, A. Optical window preparation for two-photon imaging of microglia in mice. (2012) Cold Spring Harbor Protocols. 2012(5). DOI: 10.1101/pdb.prot069286
Nimmerjahn, A. Surgical implantation of a head plate in mice in preparation for in vivo two-photon imaging of microglia. (2012) Cold Spring Harbor Protocols. 2012(5). DOI: 10.1101/pdb.prot069278
Nimmerjahn, A., Helmchen, F. In vivo labeling of cortical astrocytes with sulforhodamine 101 (SR101). (2012) Cold Spring Harbor Protocols. 2012(3):326-34. DOI: 10.1101/pdb.prot068155
Kerr, J.N., Nimmerjahn, A. Functional imaging in freely moving animals. (2012) Current Opinion in Neurobiology. 22(1):45-53. DOI: 10.1016/j.conb.2011.12.002
Tremblay, M., Stevens, B., Sierra, A., Wake, H., Bessis, A., Nimmerjahn, A. The role of microglia in the healthy brain. (2011) Journal of Neuroscience. 31(45):16064-9. DOI: 10.1523/JNEUROSCI.4158-11.2011
Ghosh, K.K., Burns, L.D., Cocker, E.D., Nimmerjahn, A., Ziv, Y., Gamal, A.E., Schnitzer, M.J. Miniaturized integration of a fluorescence microscope. (2011) Nature Methods. 8(10):871-8. DOI: 10.1038/nmeth.1694
Mukamel, E.A., Nimmerjahn, A., Schnitzer, M.J. Automated analysis of cellular signals from large-scale calcium imaging data. (2009) Neuron. 63(6):747-60. DOI: 10.1016/j.neuron.2009.08.009
Nimmerjahn, A., Mukamel, E.A., Schnitzer, M.J. Motor behavior activates Bergmann glial networks. (2009) Neuron. 62(3):400-12. DOI: 10.1016/j.neuron.2009.03.019
Nimmerjahn, A. Astrocytes going live: advances and challenges. (2009) Journal of Physiology. 587(Pt 8):1639-47. DOI: 10.1113/jphysiol.2008.167171
Flusberg, B.A., Nimmerjahn, A., Cocker, E.D., Mukamel, E.A., Barretto, R.P., Ko, T.H., Burns, L.D., Jung, J.C., Schnitzer, M.J. High-speed, miniaturized fluorescence microscopy in freely moving mice. (2008) Nature Methods. 5(11):935-8. DOI: 10.1038/nmeth.1256
Sullivan, M.R., Nimmerjahn, A., Sarkisov, D.V., Helmchen, F., Wang, S.S. In vivo calcium imaging of circuit activity in cerebellar cortex. (2005) Journal of Neurophysiology. 94(2):1636-44. DOI: 10.1152/jn.01013.2004
Nimmerjahn, A., Kirchhoff, F., Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. (2005) Science. 308(5726):1314-8. DOI: 10.1126/science.1110647
Dittgen, T., Nimmerjahn, A., Komai, S., Licznerski, P., Waters, J., Margrie, T.W., Helmchen, F., Denk, W., Brecht, M., Osten, P. Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo. (2004) Proceedings of the National Academy of Sciences of the United States of America. 101(52):18206-11. DOI: 10.1073/pnas.0407976101
Göbel, W., Kerr, J.N., Nimmerjahn, A., Helmchen, F. Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective. (2004) Opt Lett. 29(21):2521-3.
Nimmerjahn, A., Kirchhoff, F., Kerr, J.N., Helmchen, F. Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo. (2004) Nature Methods. 1(1):31-7. DOI: 10.1038/nmeth706
Göbel, W., Nimmerjahn, A., Helmchen, F. Distortion-free delivery of nanojoule femtosecond pulses from a Ti:sapphire laser through a hollow-core photonic crystal fiber. (2004) Optics Letters. 29(11):1285-7.
Kim, J., Dittgen, T., Nimmerjahn, A., Waters, J., Pawlak, V., Helmchen, F., Schlesinger, S., Seeburg, P.H., Osten, P. Sindbis vector SINrep(nsP2S726): a tool for rapid heterologous expression with attenuated cytotoxicity in neurons. (2004) Journal of Neuroscience Methods. 133(1-2):81-90.