Ensemble place codes in hippocampus: CA1, CA3, and dentate gyrus place cells have multiple place fields in large environments

Abstract

Previously we reported that the hippocampus place code must be an ensemble code because place cells in the CA1 region of hippocampus have multiple place fields in a more natural, larger-than-standard enclosure with stairs that permitted movements in 3-D. Here, we further investigated the nature of hippocampal place codes by characterizing the spatial firing properties of place cells in the CA1, CA3, and dentate gyrus (DG) hippocampal subdivisions as rats foraged in a standard 76-cm cylinder as well as a larger-than-standard box (1.8 m×1.4 m) that did not have stairs or any internal structure to permit movements in 3-D. The rats were trained to forage continuously for 1 hour using computer-controlled food delivery. We confirmed that most place cells have single place fields in the standard cylinder and that the positional firing pattern remapped between the cylinder and the large enclosure. Importantly, place cells in the CA1, CA3 and DG areas all characteristically had multiple place fields that were irregularly spaced, as we had reported previously for CA1. We conclude that multiple place fields are a fundamental characteristic of hippocampal place cells that simplifies to a single field in sufficiently small spaces. An ensemble place code is compatible with these observations, which contradict any dedicated coding scheme.

Figure 1. Spatial representation with dedicated place coding versus ensemble place coding.

Only ensemble place codes can accurately represent location if place cells have multiple firing fields, but both ensemble and dedicated place codes are accurate if place cells have single place fields. The schematics represent a moment when three place cells discharge. Artificial rasters depict discharge of three color-coded place cells and the moment (black rectangle) that position is being estimated. The place fields of the three cells are depicted along with the subject's current location (white X), the estimate of the location (black dot), and the error of the estimate (black line). A) Given a dedicated place code, averaging the independent location estimates from each cell (corresponding-colored non-transparent dots) provides an accurate estimate of the subject's location if each cell has only one place field (left), in contrast, the location estimate is typically inaccurate if the cells have multiple place fields (right). In this depiction, each independent location estimate is the centroid of the cell's place fields. B) Given an ensemble place code, the across-cell activity pattern represents location and such place codes can work equally well if the cells have single or multiple place fields . In the case that is depicted, all three cells tend to discharge together in just one region.

Figure 2. Computer-controlled foraging behavior.

A) Examples of a rat's path through the box during its first 3 exposures. This rat learned to forage throughout the box rapidly. By the third 60-min session the rat was foraging throughout the box. B) Spatial exploration throughout the box improved rapidly with the computer-controlled foraging we implemented (F_7,28 = 41.7, p = 10⁻¹³).

Figure 3. Examples of A) CA1, B) CA3, and C) DG spatial firing patterns in the cylinder and box.

A histological section illustrating the recording location as well as five simultaneously-recorded place cells is given for each example. The number below each firing rate map is the lowest rate in the red color category.

Figure 4. Comparison of CA1, CA3, and DG average place field properties in the cylinder and box.

Place field A) number; B) size; and C) spatial organization, D) proportion of active pixels.

Figure 5. Comparison of CA1, CA3, and DG spatial discharge quality in the cylinder and box.

Place field A) coherence; B) location-independent rate; C) information content; and D) rate change ratio (change in firing across environments).

Figure 6. An example of remapping in an ensemble of DG cells.

A) The standard and B) the altered visual environments. The blue-to-red color-coded firing rate maps are shown for a 9-cell ensemble of place cells that were recorded from the region of the dentate gyrus. The maps illustrate remapping between the two environments. The number below each map is the lowest rate in the red color category.