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Biophysical properties of entorhinal cortex neurons and their relationship to the representation of space

Lisa M Giocomo

Center for Memory and Brain, Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory, Norway


Grid cells in medial entorhinal cortex (MEC) fire in spatially specific locations in a repeating hexagonal grid, with smaller spacing between grid fields for neurons in more dorsal anatomical locations and larger spacing between grid fields for neurons in more ventral anatomical locations (Hafting et al., 2005; Sargolini et al., 2006). Single cell recordings using whole-cell patch clamp techniques demonstrate a correlation between intrinsic properties dependent on the hyperpolarization-activated cation current (Ih) and the topographical organization of grid cell field spacing along the dorsal-ventral axis of MEC (Giocomo et al., 2007; Giocomo & Hasselmo, 2008a, 2008b). Changes in these intrinsic properties correlate within a single cell and suggest intrinsic mechanisms for grid cell formation.  In slice recordings, knockout of the HCN1 subunit which contributes to generating Ih reduces the dorsal-ventral gradients in intrinsic properties (Giocomo & Hasselmo, 2009). To test the role of Ih and intrinsic properties in determining the properties of the grid cell field spacing topography along the dorsal-ventral axis in vivo, we recorded grid cells along the dorsal-ventral axis of layer II/III MEC in forebrain restricted HCN1 knockout mice and matched wild type littermates. We found a significant increase in grid cell field spacing in HCN1 knockout mice, suggesting the amplitude or kinetics of Ih play a significant role in setting the spacing of grid cell periodicity.

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F. Sargolini et al., Science 312, 758 (2006)

L. M. Giocomo et al., Science 315, 1713 (2007)

L. M. Giocomo & M. E. Hasselmo, J Neurosci 28, 3141 (2008a)

L. M. Giocomo & M. E. Hasselmo, Hippocampus 18, 1186 (2008b)

L. M. Giocomo & M. E. Hasselmo, J Neurosci 29, 7625 (2009)