Repeating spatial activations in human entorhinal cortex

Abstract

The ability to remember and navigate spatial environments is critical for everyday life. A primary mechanism by which the brain represents space is through hippocampal place cells, which indicate when an animal is at a particular location. An important issue is understanding how the hippocampal place-cell network represents specific properties of the environment, such as signifying that a particular position is near a doorway or that another position is near the end of a corridor. The entorhinal cortex (EC), as the main input to the hippocampus, may play a key role in coding these properties because it contains neurons that activate at multiple related positions per environment. We examined the diversity of spatial coding across the human medial temporal lobe by recording neuronal activity during virtual navigation of an environment containing four similar paths. Neurosurgical patients performed this task as we recorded from implanted microelectrodes, allowing us to compare the human neuronal representation of space with that of animals. EC neurons activated in a repeating manner across the environment, with individual cells spiking at the same relative location across multiple paths. This finding indicates that EC cells represent non-specific information about location relative to an environment's geometry, unlike hippocampal place cells, which activate at particular random locations. Given that spatial navigation is considered to be a model of how the brain supports non-spatial episodic memory, these findings suggest that EC neuronal activity is used by the hippocampus to represent the properties of different memory episodes.

Figure 1. Behavioral task and performance

(A) An overhead schematic of the layout of the virtual environment. Red squares represent locations of the destination stores and white square are non-store buildings. Gray shading indicates regions of the environment where the patient could travel. (B) Subject average task performance as a function of delivery trial number. Performance is measured as the excess number of sectors traveled when searching for a destination store, compared to an ideal path. Error bars are 95% confidence intervals. See also Figure S1.

Figure 2. Path equivalent cell firing rate maps

Top Row: Activity of a cell in patient 2’s entorhinal cortex. (A) Two dimensional firing rate map for epochs of clockwise (left) and counterclockwise (right) movement. (B) Linearized firing rate maps (smoothed with a 12-pt window) for epochs of clockwise (left) and counterclockwise (right) movement. Sides with regions of significantly elevated firing are shown in color, and sides without significant activations are in grayscale. (C) Firing rate as a function of distance from the beginning of the side, plotted separately for each side of the environment and for clockwise (bottom) and counterclockwise (top) directions. Middle Row: Activity of a cell in patient 2’s entorhinal cortex. Bottom Row: Activity of a cell in patient 5’s cingulate cortex. See also Figure S2.

Figure 3. Examples of path equivalent cells

(A) A cell from patient 1’s cingulate cortex during clockwise movement. (B) A cell from patient 2’s entorhinal cortex during counterclockwise movement. (C) A cell from patient 2s entorhinal cortex during clockwise movement. (D) A cell from patient 5’s entorhinal cortex during clockwise movement. (E) A cell from patient 10’s parahippocampal gyrus during clockwise movement. (F) A cell from patient 12’s entorhinal cortex during counterclockwise movement. (G) A cell from patient 13’s hippocampus during clockwise movement. (H) A cell from patient 13’s hippocampus during counterclockwise movement. See figure S3 for additional examples.

Figure 4. Population measurements

(A) Regional distribution of path-equivalent cells, which are location-responsive cells that have correlated responses across multiple corridors in the environment. EC: entorhinal cortex; H: hippocampus; PHG: parahippocampal gyrus; A: amygdala; CC: cingulate cortex; Cx: frontal/lateral-temporal cortex. (B) The percent of corridor pairs with place fields at the same relative locations. This measure is computed by identifying each cell with place fields on at least two corridors and measuring, across all pairs of corridors, how often place fields occur at the same relative location. ** denotes p<.0001, * denotes p<.05. See also Figure S4 and Table S1.