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

Biophysical properties underlying the representation of space in entorhinal cortex

Tildelt: kr 1,6 mill.

In 2004-2005, behavioral unit recordings of rats exploring large open fields demonstrated that medial entorhinal cortex (mEC) 'grid cells' fire in spatially specific locations which repeat at regular intervals and form a hexagonal shape of firing activity and potentially provide the basic building blocks of spatial representation. The field size and spacing of the grid cell firing field increases from small in dorsal portions of medial entorhinal cortex to large in ventral medial entorhinal cortex. The c hange in field size and spacing of the grids from small to large along the dorsal-ventral axis of mEC, allows these cells to dynamically represent the entire spatial environment. Single cell recordings of mEC neurons using whole-cell patch clamp techniq ues demonstrated that the intrinsic properties of these cells, dependent the hyperpolarization activated cation current I(h), also systematically change along the dorsal-ventral axis, and the changes in intrinsic properties correlate with the dorsal-ventr al change in grid cell field size and spacing. Recent research demonstrating that the subunit composition (HCN1, HCN2) can effect the kinetics of I(h) provides a molecular target for investigating how single cell kinetics contribute to spatial memory. Nov el techniques employed include virus-based in vivo over-expression or knockdown to modulate the ratio of subunits with faster (HCN1) or slower (HCN2) kinetics, which could result in a change in the spatial periodicity of grid cells in mEC. Due to the nove l aspect of the viral work, examination of the kinetics in HCN1 knockout mice will complement findings using viral technology. Using novel viral technology, manipulation of the kinetics of I(h) will test the hypothesis that single cell kinetics contribute to spatial memory at the network level, possibly providing one of the first sets of data showing how specific ion channel kinetics can affect the output at the network level.


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