Time Cells in the Retrosplenial Cortex

Abstract

The retrosplenial cortex (RSC) is a key component of the brain's memory systems, with anatomical connections to the hippocampus, anterior thalamus, and entorhinal cortex. This circuit has been implicated in episodic memory and many of these structures have been shown to encode temporal information, which is critical for episodic memory. For example, hippocampal time cells reliably fire during specific segments of time during a delay period. Although RSC lesions are known to disrupt temporal memory, time cells have not been observed there. In the present study, we examined the firing patterns of RSC neurons during the intertrial delay period of two behavioral tasks, a blocked alternation task and a cued T-maze task. For the blocked alternation task, rats were required to approach the east or west arm of a plus maze for reward during different blocks of trials. Because the reward locations were not cued, the rat had to remember the goal location for each trial. In the cued T-maze task, the reward location was explicitly cued with a light and the rats simply had to approach the light for reward, so there was no requirement to hold a memory during the intertrial delay. Time cells were prevalent in the blocked alternation task, and most time cells clearly differentiated the east and west trials. We also found that RSC neurons could exhibit off-response time fields, periods of reliably inhibited firing. Time cells were also observed in the cued T-maze, but they were less prevalent and they did not differentiate left and right trials as well as in the blocked alternation task, suggesting that RSC time cells are sensitive to the memory demands of the task. These results suggest that temporal coding is a prominent feature of RSC firing patterns, consistent with an RSC role in episodic memory.

Keywords: episodic memory; retrosplenial cortex; temporal coding; temporal context; time cells.

Figure 1.

Retrosplenial Time Cells in the blocked alternation task. Plot A shows examples of RSC time cells observed in the blocked alternation task. The firing rate heatmaps illustrate trial by trial firing, shown separately for the ‘Go East’ and ‘Go West’ conditions. The line plot shows the average firing rate across trials with the two vertical black lines indicating the boundaries of the time field. Because the delay duration was variable, average firing rate was calculated only for time periods containing at least two thirds of the trials. Neurons could have more than one time field (e.g. plot 8). Plots 9 and 10 illustrate example neurons with off-response time fields, in which firing was reliably suppressed during a well-defined part of the delay. Plot B & D illustrate the temporal firing of all the neurons with significant on-response (B) and off-response (D) time fields across the first 20 seconds of intertrial delay period. Each row illustrates the normalized firing rate of a single neuron, averaged across all trials, and sorted according to the time of maximum (B) or minimum (D) firing. Plot C shows two example neurons with time fields aligned to the end of the delay period. For each neuron, the start-aligned firing is plotted on the left and the same data re-aligned to the end of the delay is plotted on the right. The neuron in plot 1 had a time field aligned to the start of the delay on the east trials, along with a time field aligned to the end of the delay for both trial types. Plot E shows the percentage of time cells that showed differential firing for the on-response and off-response time cells. Plot F shows the percentage of time cells observed in putative pyramidal neurons and interneurons, with on- and off-responses shown in blue and yellow, respectively.

Figure 2.

Retrosplenial Time Cells in the cued T-maze task. Plot A illustrates example time cells observed in the cued T-maze task. Firing rate heatmaps are illustrated as in figure 1, with separate plots for right and left trials. Plot B illustrates the temporal firing of all the neurons with significant on-response time fields. Only two neurons were found to have off-response time fields in this task (not shown).

Figure 3.

Time cell characteristics differ across behavioral tasks. The percentage of neurons with significant time cells in each task are shown, with on- and off-response time cells shown in blue and yellow, respectively, and differential firing across the east/west or left/right conditions indicated by diagonal lines.

Figure 4.

Spatial firing in RSC time cells. Spatial firing patterns observed during the trials are shown for four example neurons with time fields during the intertrial delay period. Plot 1 is the same neuron illustrated in figure 1C, plot 1. Plot 4 is an example neuron from the cued T-maze task.