Final Report Summary - ENTORHINAL CIRCUITS (Spatial representation in the entorhinal neural circuit)
The research conducted during this Fellowship concentrated specifically on the representation of space by individual medial entorhinal cortex (MEC) neurons called 'grid cells' (Fyhn et al., Science, 2004). As an animal explores an environment, grid cells fire in spatially specific locations which repeat at regular intervals and form a gird-like pattern of firing activity tiling the entire environment. Despite constant changes in the animal's speed and direction, the grid cell firing pattern retains rigidly periodic firing fields, suggesting that the grid representation is generated from within the entorhinal circuit. Thus, grid cells provided an ideal model for investigation into cellular and molecular mechanisms contributing to the output of cortical circuits.
In all environments, the spatial scale of the grid cells is organized topographically along the dorsal-ventral axis of the MEC (Hafting et al., Science, 2005). Grid scale is characterized by the size of the individual firing fields as well as the distance, or spacing, between the grid vertices. Both grid-field size and grid spacing increase progressively from dorsal to ventral MEC. Recordings using whole-cell patch clamp techniques of single MEC cells 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-ventral change in grid cell field size and spacing (Giocomo et al., Science, 2007). During my Marie Curie Fellowship, I continued my previous work on the topographical organization in cellular properties and their relationship to the network level phenomena of grid cells. I first conducted in vitro whole cell patch clamp recordings demonstrating that the gradients in multiple single cell properties are dependent on or modulated by the presence of a subunit which conducts Ih (HCN1) (Giocomo and Hasselmo, Journal of Neuroscience, 2009). Next, my colleagues and I discovered that the knockout of HCN1 in vivo results in a significant increase in the distance between the firing nodes of grid cells, indicating that HCN1 contributes to the scale of spatial representation in the entorhinal circuit (Giocomo et al., submitted). The increase in grid spacing with a loss of HCN1 additionally raise the possibility that, during self-motion-based navigation, Ih contributes to the gain of the transformation from movement signals to spatial firing fields. The role of HCN1 in the representation of space discovered during this project offers unique insights into some of the fundamental principles of neuronal assembly and microcircuit operation in the mammalian cortex.
In all environments, the spatial scale of the grid cells is organized topographically along the dorsal-ventral axis of the MEC (Hafting et al., Science, 2005). Grid scale is characterized by the size of the individual firing fields as well as the distance, or spacing, between the grid vertices. Both grid-field size and grid spacing increase progressively from dorsal to ventral MEC. Recordings using whole-cell patch clamp techniques of single MEC cells 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-ventral change in grid cell field size and spacing (Giocomo et al., Science, 2007). During my Marie Curie Fellowship, I continued my previous work on the topographical organization in cellular properties and their relationship to the network level phenomena of grid cells. I first conducted in vitro whole cell patch clamp recordings demonstrating that the gradients in multiple single cell properties are dependent on or modulated by the presence of a subunit which conducts Ih (HCN1) (Giocomo and Hasselmo, Journal of Neuroscience, 2009). Next, my colleagues and I discovered that the knockout of HCN1 in vivo results in a significant increase in the distance between the firing nodes of grid cells, indicating that HCN1 contributes to the scale of spatial representation in the entorhinal circuit (Giocomo et al., submitted). The increase in grid spacing with a loss of HCN1 additionally raise the possibility that, during self-motion-based navigation, Ih contributes to the gain of the transformation from movement signals to spatial firing fields. The role of HCN1 in the representation of space discovered during this project offers unique insights into some of the fundamental principles of neuronal assembly and microcircuit operation in the mammalian cortex.