Theta guided sequences in the medial entorhinal cortex

Abstract

Grid cells in the medial entorhinal cortex (mEC) fire at the vertices of a hexagonal grid that tiles the entire space an animal explores. This pattern serves as an allocentric coordinate system for animals to integrate their movement and determine their current location even in the absence of external cues. The stability and precision of this pattern is remarkable given many experimentally measured variables in the mEC - inputs to stellate cells and variability of local field potential oscillations - vary noisily as the animal navigates its environment. How can a stable spatial representation be built upon such shaky ground? We discover that the answer lies in the interplay between theta oscillations and the intrinsic time scales of the system, namely, the conductances expressed in stellate cells. To illustrate the mechanism we simulate a network of physiologically detailed conductance based model stellate cells coupled via inhibitory interneurons. Competitive interactions between stellate cells cause different groups of neurons to fire at different times. The identity of neurons that form transiently synchronous groups is determined by the topology of inhibition and the history of activation of stellate cells. We show that these spatiotemporal sequences can be easily perturbed by noise to the network. Theta oscillations are required to ensure that the same sequence is stimulated every time the animal traverses a particular trajectory. The reliability of these temporal sequences, in turn, translates into the stability of the grid cell’s spatially periodic receptive field. Theta oscillations are themselves fickle, in that, the phase of theta is not pinned to the location of the animal as the spiking activity of grid cells are. Further, changes in movement velocity affect the frequency of theta oscillations. We show that these perturbations to theta do not affect the stability of grid fields. Our simulations concur with experimental data demonstrating that when theta oscillations are selectively and reversibly removed by excising input from the medial septum, grid fields dissipate leaving spatially non-specific and temporally imprecise patterns of activity. Our model shows that the formation of spatially periodic receptive fields is an emergent property of the coupling between theta oscillations and the intrinsic rich temporal repertoire of the mEC network.