PROJECT B6

Functional plasticity of glutamate receptor channels on hippocampal mossy fiber terminals

Project Description
Principal Investigator(s)
Publications


Mossy fiber boutons (MFBs) of hippocampal granule cells (GCs) in the dentate gyrus (DG) are uniquely plastic and play a key role in creating and retrieving memories. MFB plasticity is controlled by presynaptic ionotropic glutamate receptors of the kainate subtype (GluKs). GluKs are autoreceptors for presynaptically released glutamate and may enhance or suppress release in a context-dependent manner. We focus on GluKs, active zones (AZs) and MFB plasticity. AZs couple presynaptic calcium inflow and vesicle fusion. Changes in size, molecular composition, number and function of AZs may contribute to MFB plasticity. However, the connection of AZ-plasticity and GluKs is not well understood.

We aim to: A) Obtain functional (electrophysiological) and optical receptor counts (with GluK-antibodies and dSTORM-imaging) for molecularly defined homo- and heteromeric GluKs in outside-out patches from transiently transfected HEK293-cells. B) Map presynaptic GluKs in MFBs relative to the core AZ components Bassoon and Rab3-interacting molecule 1/2α (RIM1/2α) using cryo-sections from adult mouse brains, antibodies and dSTORM-imaging. C) Record from GCs and MFBs in acute hippocampal slices using patch-clamp recordings to correlate synaptic function and dSTORM-protein maps. Thus we hope to elucidate nanoscopic protein dynamics at the level of individual AZs, the role of GluKs and the impact of both on MFB plasticity and memory.

Prof. Dr. Heckmann, Manfred

heckmann@uni-wuerzburg.de

Manfred Heckmann will coordinate and supervise the project together with other members of the team.


Prof. Dr. Sirén, Anna-Leena

siren.a@nch.uni-wuerzburg.de

Anna-Leena Sirén will coordinate and supervise the project together with other members of the team.


Title Year Authors Journal Links
Synaptic Vesicle Proteins and Active Zone Plasticity 2016 Kittel, R. J. and Heckmann, M. Front Synaptic Neurosci More
Human autoantibodies to amphiphysin induce defective presynaptic vesicle dynamics and composition 2016 Werner, C., Pauli, M., Doose, S., Weishaupt, A., Haselmann, H., Grunewald, B., Sauer, M., Heckmann, M., Toyka, K. V., Asan, E., Sommer, C., and Geis, C. Brain More
Nanodomain coupling at an excitatory cortical synapse 2013 Schmidt, H., Brachtendorf, S., Arendt, O., Hallermann, S., Ishiyama, S., Bornschein, G., Gall, D., Schiffmann, S.N., Heckmann, M., Eilers, J. Curr Biol More
Essential role for Stat5 in the neurotrophic but not in the neuroprotective effect of erythropoietin 2008 Byts, N., Samoylenko, A., Faßhauer, T., Ivanisevic, M., Hennighausen, L., Ehrenreich, H., Sirén, A.-L. Cell Death and Differ More
Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle release 2006 Kittel RJ, Wichmann C, Rasse TM, Fouquet W, Schmidt M, Schmid A, Wagh DA, Pawlu C, Kellner RR, Willig KI, Hell SW, Buchner E, Heckmann M, Sigrist SJ. Science More
A hematopoietic growth factor, thrombopoietin, has a pro-apoptotic role in the brain 2005 Ehrenreich, H., Hasselblatt, M., Knerlich, F., von Ahsen, N., Jacob, S., Sperling, S., Woldt, H., Vehmeyer, K., Nave, K.-A., Sirén, A.-L. Proc Natl Acad Sci USA More
Erythropoietin: A candidate compound for neuroprotection in schizophrenia 2004 Ehrenreich, H., Degner, D., Meller, J., Brines, M., Béhé, M., Hasselblatt, M., Woldt, H., Falkai, M., Knerlich, F., Jacob, S., von Ahsen, N., Maier, W., Brück, W., Rüther, E., Cerami, A., Becker, W., Sirén, A.-L. Mol Psychiat More
A large pool of releasable vesicles in a cortical glutamatergic synapse 2003 Hallermann, S., Pawlu, C., Jonas, P., Heckmann, M. Proc Natl Acad Sci USA More
Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress 2001 Sirén, A.-L., Fratelli, M., Brines, M., Goemans, C., Casagrande, S., Lewczuk, P., Keenan, S., Gleiter, C., Pasquali, C., Capobianco, A., Mennini, T., Heumann, R., Cerami, A., Ehrenreich, H., Ghezzi, P. Proc Natl Acad Sci USA More
Erythropoietin and erythropoietin receptor expression in human ischemic/hypoxic brain 2001 Sirén, A.-L., Knerlich, F., Poser, W., Gleiter, C.H., Brück, W., Ehrenreich, H. Acta Neuropathol More
Kinetics of homomeric GluR6 glutamate receptor channels 1996 Heckmann, M., Bufler, J., Franke, C., Dudel, J. Biophys J More