Behavioral unit recordings of rats exploring an open field have shown that medial entorhinal cortex (mEC) neurons have spatially specific firing fields that repeat at regular intervals. Called ‘grid cells’, the field size and spacing of firing activity changes along the dorsal-ventral axis of mEC. In vitro recordings of the same cell population has shown dorsal-ventral changes in the intrinsic properties of the cells; subthreshold oscillation frequency and the time constant of the hyperpolarization activated cation current I(h), which correlate with the dorsal-ventral change in grid cell firing activity. Recent research demonstrating that the subunit composition (HCN1, HCN2) can effect the temporal kinetics of I(h) provides a molecular target for investigating how single cell kinetics contribute to spatial memory. In vivo over-expression or knockdown used to modulate the ratio of subunits with faster (HCN1) or slower (HCN2) I(h) kinetics should result in a change in the spatial periodicity of grid cells in mEC. A higher proportion of subunits with fast kinetics should result in grid cells with smaller field size and spacing, while a higher proportion of subunits with slow kinetics should result in the opposite. Examination of the kinetics in HCN1 knockout mice will complement findings using viral technology. While research has shown a clear correlation between intrinsic cellular property changes and grid cell field size changes, no experimental evidence yet indicates a causal relationship between the two sets of data. Manipulation of the kinetics of I(h) will test the hypothesis that single cell kinetics contribute to spatial memory at the network level.
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