Project Details
Projekt
Alterations of synaptic and network functions in APP and APLP-deficient mice
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2010 to 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 138733498
We want to elucidate the role of APP (and its fragments) and APLP2 for physiological functions of the mouse hippocampus. Therefore, we will combine our complementary expertise to study genetically modified animals and cells, provided by U. Müller. We hypothesize that deficiency in APP or APLP causes changes in baseline synaptic properties, excitation-inhibition-balance, short- and long-term synaptic plasticity and, as a consequence, in different patterns of memory-related network activity. Cells from the lethal APP/APLP2- DKO double mutants will be analyzed in hippocampal cell cultures. The expected alterations of inhibitory and excitatory synaptic currents will serve as a baseline for further experiments on brain slices, using viable APPsα-KI/APLP2-KO mutant mice. Abnormalities in these mice will shed light on the (overlapping) function of APP and APLP2. A similar analysis will be done in conditional CamKlI-CreERT2 APPflox mice on an APLP2-KO background which lose APP in the forebrain in the presence of tamoxifen. Finally, triple-deficient ES cells (generated by U. Müller and B. DeStrooper) will be differentiated into neurons and will be studied after transplantation into organotypic hippocampal slice cultures. Together, our data shall reveal the functional importance of the APP/APLP protein family at the cellular and network level.
DFG Programme
Research Units
