PROJECT B6
Functional plasticity of glutamate receptor channels on hippocampal mossy fiber terminals
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.
