Temporal Frequency of Subthreshold Oscillations Scales with Entorhinal Grid Cell Field Spacing

Abstract

SummaryIntracellular recording shows how differences in single cell subthreshold oscillation frequency could directly underlie the differences in spacing of grid cell firing locations shown previously in awake, behaving animals.Grid cells in layer II of entorhinal cortex fire to spatial locations in a repeating hexagonal grid with smaller spacing between grid fields for neurons in more dorsal anatomical locations. Data from in vitro whole-cell patch recordings show a corresponding difference in frequency of subthreshold membrane potential oscillations in entorhinal neurons at different positions along the dorsal to ventral axis, supporting a model of physiological mechanism for grid cell responses.The entorhinal cortex plays an important role in encoding of spatial information (1-3) and episodic memory (4). Many layer II neurons of rat entorhinal cortex are "grid cells," firing when the rat is in an array of spatial locations forming a hexagonal grid within the environment (5-7). The spacing of firing fields in the grid varies with anatomical position of the cell along the dorsal to ventral axis of entorhinal cortex, as measured by distance from the postrhinal border (5). Neurons closer to the dorsal border of entorhinal cortex have shorter distances between firing fields. Computational models explicitly predict that differences in grid field spacing should correspond to differences in intrinsic frequencies of neurons along the dorsal to ventral axis (3,8). This could provide systematic variation in the gain of a movement-speed signal for path integration (2,3,9).Subthreshold membrane potential oscillations in entorhinal cortical stellate cells (10) arise from a single-cell mechanism involving voltage-sensitive currents (11-13) and could contribute to network dynamics (14). We recorded subthreshold oscillations from 57 stellate cells in layer II of medial entorhinal cortex (Fig. S1) in slices from different anatomical positions along the dorsal to ventral axis, using whole-cell patch clamp techniques (15). The position of individual horizontal slices was measured relative to the dorsal surface of the brain (Fig. 1A).Stellate cells in dorsal entorhinal cortex show higher temporal frequencies of subthreshold membrane potential oscillations compared to lower frequencies in cells from more ventral entorhinal slices (Fig. 1B). Dorsal cells (n = 30) are defined as cells recorded in slices taken between 3.8 mm (the border with postrhinal cortex (16)) and 4.9 mm from the dorsal surface of the brain. Ventral cells (n = 27) are defined as cells recorded in slices between 4.9 and 7.1 mm from the dorsal surface. Fig. 1B shows the group means of the frequency of subthreshold oscillations recorded from these populations. Because frequency of subthreshold oscillations can depend upon the mean membrane potential voltage, we performed this analysis separately for data gathered at different approximate holding membrane potentials of −50 mV and −45 mV. The mean frequency in dorsal cells was significantly higher than the mean frequ...

Towards a functional organization of the medial temporal lobe memory system: Role of the parahippocampal and medial entorhinal cortical areas

“…While it is not at all clear why the firing patterns of MEC neurons have a grid-like structure, one suggestion is that this pattern is a consequence of oscillatory interference in the theta rhythms in distinct MEC laminae, combined with spatial signals of head direction and velocity Giocomo et al, 2007; see also Burgess, 2008). Notably, the strict and consistent grid pattern may be limited to situations where animals continuously move through open fields and linear tracks, and that the multipeaked spatial firing pattern becomes more complex under circumstances where continuous movements are interrupted by turns and stops (Derdikman et al, 2006), which are prevalent characteristics of behavioral tasks where memory is involved (Lipton et al, 2007).…”

Grid cell mechanisms and function: Contributions of entorhinal persistent spiking and phase resetting

“…Previous modeling showed that membrane potential oscillations in entorhinal neurons might also contribute to grid cell firing Giocomo et al, 2007;Hasselmo et al, 2007;Giocomo and Hasselmo, 2008a). Entorhinal Layer II stellate cells show subthreshold membrane potential oscillations when depolarized near firing threshold (Alonso and Llinas, 1989;Alonso and Klink, 1993;Giocomo et al, 2007).…”

“…Entorhinal Layer II stellate cells show subthreshold membrane potential oscillations when depolarized near firing threshold (Alonso and Llinas, 1989;Alonso and Klink, 1993;Giocomo et al, 2007). These subthreshold oscillations can influence the timing of action potentials and network oscillations (Alonso and Garcia-Austt, 1987;Acker et al, 2003).…”

“…The frequency of membrane potential oscillations differs systematically along the dorsal to ventral axis of the medial entorhinal cortex Giocomo and Hasselmo, 2008a). Previous modeling showed how these differences in membrane potential oscillation frequency could underlie differences in grid cell spatial periodicity along the dorsal to ventral axis Giocomo et al, 2007;Hasselmo et al, 2007;Giocomo and Hasselmo, 2008a). The oscillations appear to be due to a hyperpolarization-activated cation current known as the h-current (Dickson et al, 2000) that differs in time constant along the dorsal to ventral axis (Giocomo and Hasselmo, 2008b).…”

The role of ongoing dendritic oscillations in single-neuron dynamics

“…Indeed, multiple intrinsic dendritic oscillators have been proposed to underlie the recently discovered intricate firing pattern of entorhinal grid cells [22,23,24]. Motivated by the likely existence of multiple dendritic oscillators in a single cell, we study the dynamics of such interacting oscillators and their impact on signal propagation in single neurons, using mathematical analysis corroborated by numerical simulations of biophysical models.…”