Multiplexing of temporal and spatial information in the lateral entorhinal cortex

Abstract

Episodic memory involves the processing of spatial and temporal aspects of personal experiences. The lateral entorhinal cortex (LEC) plays an essential role in subserving memory. However, the mechanisms by which LEC integrates spatial and temporal information remain elusive. Here, we recorded LEC neurons while male rats performed one-dimensional tasks. Many LEC cells displayed spatial firing fields and demonstrated selectivity for traveling directions. Furthermore, some LEC neurons changed the firing rates of their spatial rate maps during a session (rate remapping). Importantly, this temporal modulation was consistent across sessions, even when the spatial environment was altered. Notably, the strength of temporal modulation was greater in LEC compared to other brain regions, such as the medial entorhinal cortex, CA1, and CA3. Thus, we demonstrate spatial rate mapping in LEC neurons, which may serve as a coding mechanism for temporal context, and allow for flexible multiplexing of spatial and temporal information.

Fig. 1. Spatial firing of LEC neurons in one-dimensional apparatus.

a Schematics of the double rotation task. Three standard (STD) sessions were interleaved with two mismatch (MIS) sessions. In the MIS sessions, local cues on the track were rotated counterclockwise and the global cues along the curtain at the periphery of the room (the black outer ring) were rotated clockwise. The subjects foraged for food scattered at arbitrary locations on the track (~2 rewards/lap) while moving clockwise. b The circular track task. Two sessions recorded in the light condition were separated by a session in the dark. c Linear track. For both the circular track and linear track, the animals shuttled back and forth to retrieve food pellets in the food wells placed at the ends of the journeys. d Spatial firing patterns of three example LEC neurons in the double rotation task. For each cell, the spatial rate map of the session is shown at the top (the number on top indicates the spatial information score) and the lap-wise spatial rate map is shown at the bottom (the number on top shows the peak firing rate of the map). e The session-wise spatial rate maps and lap-wise spatial rate maps of two LEC cells in the circular track task. The rate maps of the two movement directions are separately shown for each cell. f Histograms of the distribution of spatial information scores for all LEC neurons in the three behavioral tasks. Source data are provided as a Source Data file.

Fig. 2. Directional preferences of LEC cells in 1-dimensional shuttling tasks.

a Left, four example LEC neurons showing directionally selective firing on the circular track. Shaded red and blue colors denote the mean ± SEM for counterclockwise and clockwise movement, respectively. The black line denotes the difference between the firing rates for the two directions. Colored lines and dotted lines are thresholds for detecting pointwise and family-wise significant regions, respectively. Bold color lines at the top denote regions of significant direction selectivity. Right, four neurons with direction selectivity in linear track paradigm. Same conventions as for the circular track (left). b Distribution of locations with peak direction selectivity index (see Methods) for each cell on the circular track. c Same as Fig. 3b for the linear track. d Four example LEC neurons with strong distance coding in the circular track task. All four cells fired comparably depending on the distance from the start of the journey. e Same as panel (d) for four cells in the linear track task. f Left: sorted spatial rate maps for the two directions in the circular track task. Right: population correlation matrix between the two directions. A high correlation in the main diagonal (bottom left to top right) indicates consistent firing at the same location for the two directions, whereas a strong signal in the minor diagonal (top left to bottom right) indicates consistent firing at the same journey distance from the track ends. g Left, the observed mean correlation of bins along the minor diagonal of the correlation matrix (i.e., from top left to lower right showing the correlation between the same distances from the start position in both directions) is shown as the red line and the null distribution is simulated with a permutation analysis. Right, the observed correlation difference (the red line) and the null distribution comparing the distance coding from the starting position (the first 4 bins) and the end position (the last 4 bins). h, i Same as panels (f) and (g) for the linear track task. Source data are provided as a Source Data file.

Fig. 3. Representation of temporal information about trial identity through rate remapping of spatial firing fields by LEC neurons.

a Three example cells. Each row shows the lap-wise spatial rate maps for an LEC neuron in three STD sessions in the double rotation task. Cell 1 decreases its firing over the laps of the session, whereas cells 2 and 3 increase their firing from near silence on lap 1 to robust firing at specific locations in later laps. b Same as panel (a) for three cells in the circular track task. Source data are provided as a Source Data file.

Fig. 4. The temporal signal carried by LEC is robust to spatial manipulations.

a Schematics for decomposition of the lap-wise spatial rate maps into spatial and temporal modulation fields. b The temporal modulation fields of six example cells across sessions in the double rotation task. Each cell shows similar temporal modulation in all sessions. c Same as panel (b) for six neurons in the circular track task. d The observed correlation (red line) and null distribution of correlations between the temporal modulation fields in two sessions in the double rotation task. Left: STD1 vs. STD2; right: STD1 vs. STD3. e Same as panel (d) for data in the circular track task. Left: Light 1 (STD1) vs. Light 2 (STD2) in direction 1; Light 1 (STD1) vs. Light 2 (STD2) in direction 2. f Same as panel (d) for correlations between temporal modulation fields in STD sessions and manipulated sessions in the double rotation task (left) and the circular track task (right). Source data are provided as a Source Data file.

Fig. 5. Spatial and temporal coding properties in the entorhinal-hippocampal regions.

a Sorted spatial modulation fields for LEC, MEC, CA3, and CA1. b Sorted temporal modulation fields for the four brain regions. c The distributions of spatial information scores across regions. Gray dots, data for each neuron; black dots, the median value. Two-sided Wilcoxon rank-sum test with Holm–Bonferroni correction, LEC vs. MEC: p < 10⁻³; LEC vs. CA1: p < 10⁻¹⁰; LEC vs. CA3: p < 10⁻¹⁰; MEC vs. CA1: p < 10⁻¹⁰; MEC vs. CA3: p < 10⁻¹⁰; CA1 vs. CA3: p < 10⁻¹⁰. d The distributions of temporal information scores across regions. LEC vs. MEC: p = 0.008; LEC vs. CA1: p = 0.015; LEC vs. CA3: p = 0.001; CA1 vs. CA3: p = 0.007. e The distributions of Pearson’s correlation coefficients between standard sessions across regions. Two-sided Wilcoxon rank-sum test with Holm–Bonferroni correction, LEC vs. MEC: p = 0.004; LEC vs. CA1: p = 0.0071; CA1 vs. CA3: p = 0.0037. ^*p < 0.05; ^**p < 0.01. Source data are provided as a Source Data file.