Multilevel analysis of memory formation in the entorhinal-hippocampal circuit

Neuronal networks within the medial temporal lobe are essential for fast encoding and storage of episodic memories in humans and other mammals. A key connection in this system is the perforant path (PP) which projects from the entorhinal cortex to the hip pocampus (including the dentate gyrus). Synapses formed by PP-fibers onto hippocampal CA1 pyramidal cells are particularly intriguing because they are able to control the firing pattern of the CA1 cells in spite of being located so distally on the dendrit es that existing knowledge cannot fully explain how they can elicit action potentials. The PP-fiber synapses onto dentate gyrus granule cells are equally intriguing both because they display prominent synaptic plasticity controlled by neurotrophic factors , and because they induce generation of new nerve cells (neurogenesis) even in the adult brain. Understanding synaptic function and plasticity in these synapses is essential for understanding memory formation and neurogenesis in the hippocampus. Our objec tive is to perform a comprehensive analysis of the functional properties of the entorhinal-hippocampal connection and its role in learning and memory. We will determine specific properties of this circuit and how its characteristics contribute to the form ation of new memories. In parallel, the project is expected to generate new knowledge about general mechanisms operating in the brain, with respect to synaptic function and plasticity, neurogenesis and repair, and information transfer between neuronal pop ulations during behavior. Our consortium is designed to combine the power of our two centres of excellence, EU and FUGE platforms, by bringing together expertise in stem cells, growth factors, construction of transgenic animals, in vivo and in vitro elect rophysiology, neuropharmacology, confocal imaging, quantitative immunocytochemical electron microscopy, fibre tracing, 3-D reconstruction, advanced databasing, computational neuroscience, and behavioral testing.