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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Dual band-pass filtering of information within cortical pyramidal neurons

Tildelt: kr 10,0 mill.

Pyramidal neurons are the principal cells the main 'computational units' - of the cerebral cortex, but how they function remains enigmatic. The present proposal aims at elucidating novel functional principles within these cells that are likely to be impor tant at two different levels: at the fundamental 'single cell computation' level, common to cortical pyramidal cells; and at the network level, specifically in the entorhinal-hippocampal system for spatial navigation and memory, which is dominated by netw orks oscillations at theta frequency (4-8 Hz). This system has become a leading model for understanding the functional principles of the mammalian cerebral cortex, and provides some of the best examples of how gaps between different levels of analysis can be bridged. Recent evidence indicates that intrinsic electrical properties of single neurons within this system may have a strong impact on network function and animal behavior. The proposed project aims at contributing to this progress. Using dual patch clamp recordings from the dendrites and soma of the same cell, combined with dynamic clamp, advanced computational modeling, and viral vecors for gene manipulation, we will test how intrinsic resonance mechanisms filter information on its way from the de ndrites to the soma and vice versa, in a frequency-dependent, voltage-dependent, and direction-dependent manner. Since the project may provide significant basic insights into mecanisms of the cerebral cortex and memory systems, it may thus contribute to a basis for improved therapies of memory impairment and other brain disorders.

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FRIMEDBIO-Fri prosj.st. med.,helse,biol

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