Place cell activation predicts subsequent memory

Abstract

A major quandary in memory research is how hippocampal place cells, widely recognized as elements of a spatial map, contribute to episodic memory, our capacity to remember unique experiences that depends on hippocampal function. Here we recorded from hippocampal neurons as rats performed a T-maze alternation task in which they were required to remember a preceding experience over a delay in order to make a subsequent spatial choice. As it has been reported previously in other variations of this task, we observed differential firing that predicted correct subsequent choices, even as the animal traversed identical locations prior to the choice. Here we also observed that most place cells also fired differently on correct as compared to error trials. Among these cells, a large majority fired strongly before the delay or during the retrieval phase but were less active or failed to activate when the animal subsequently made an error. These findings join the place cell phenomenon with episodic memory performance dependent on the hippocampus, revealing that memory accuracy can be predicted by the activation of single place cells in the hippocampus.

Keywords: Hippocampus; Place cells; Subsequent memory effect.

Figure 1

The delayed spatial alternation task. Blue: path on left to right (LR) trials; Red: path on right to left (RL) trials.

Figure 2. Spatial distributions of firing rates comparing the pattern of firing on correct trials versus errors in the delayed alternation task

A–F. Cells that fired differentially as rats traversed different parts of a return arm. A–B. Detailed descriptions are provided in the text. For other cells, correct vs. error: C. F_(1,125) = 6.15, p = 0.014; D. F_(1,189) = 6.425, p = 0.01; E. F_(1,71) = 14.31, p = 0.0003). F. This cell fired strongly only on errors and hardly on correct trials (F_(1,179) = 8.21, p = .004). G–L. Cells that fired differentially as rats traversed different parts of the maze stem. G–H. Detailed descriptions are provided in the text. I–L. Cells that fired as rats traversed different parts of the stem. I. This cell fired robustly on both LR and RL correct trials and hardly fired on errors (correct vs. error X segment: LR F_(1,359) = 18.38, p < 0.0001; RL F_(1,99) = 4.44, p = 0.00009) J. This cell fired strongly on LR but not RL correct trials and hardly fired on errors (LR correct vs. error X segment: F_(1,79) = 6.323, p = .000003; RL correct vs. error X segment: F_(1,39) = 2.8008, p = 0.026). K. This cell fired strongly as the rat approached the end of the stem on LR and RL correct trials and hardly fired on errors (LR correct vs. errors X segment: F_(9,179) = 2.469, p = 0.011; RL correct vs. errors X segment: F_(9,119) = 3.09, p = 0.00256). L. This cell had a higher firing rate when traversing the stem on LR than RL trials during correct trials, and the reverse pattern on errors (correct trials LR vs. RL X segment: F_(9,119) = 2.197, p = 0.02; LR correct vs. error: F_(1,79) = 16.62, p = 0.0001; RL correct vs. error X segment: F_(1,39) = 4.622, p = 0.002). M–R. Cells that fired differentially as rats traversed different parts of a goal arm. M–N. Detailed descriptions are provided in the text. O–P. Cells that fired similarly on correct and error trials as rats traversed the goal arm (correct vs. error: O. F_(1,99) = 0.06, p = 0.79; P. F_(1,89) = 0.06, p = 0.79). Q. A cell that fired strongly on correct trials but not errors (correct vs. errors: F_(1,59) = 5.53, p = 0.022). R. This cell had a unique firing pattern on errors and hardly fired on correct trials (correct vs. error: F_(1,59) = 7.43, p = 0.008).

Figure 3

The firing patterns of hippocampal place cells distinguish correct vs. error trials. A. Median log-likelihood ratios (upper and lower 95% CI) for place fields in different maze arms measuring strength of discrimination for correct trials versus errors. Average mean (B) and average peak (C) firing rates (± 1 S.E.) for place fields in different maze arms on correct versus error trials.

Figure 4. Examples of firing patterns observed on continuous alternation and delayed alternation (correct trials only)

A–F. Cells that fired differentially as rats traversed different parts of a return arms. A. A cell that fired as the rats was in the midst of the right return arm in the continuous task but not the delay task (F_(1,269) = 16.82, p < 0.0001) B. A cell that fired as the rats was in the midst of the right return arm in the delay task but not the continuous task (F_(1,251) = 60.33, p < 0.0001) C. A cell that fired strongly as the rats reached the end of the left return arm in the delay task and less so in the continuous task (F_(1,233) = 14.65, p < 0.0001) D. A cell that fired strongly as the rats reached the end of the left return arm in the delay task and not in the continuous task (F_(1,305) = 322.77, p < 0.0001; E. A cell that fires strongly when the rat is in the midst of the left return arm in the delay but not the continuous task (continuous vs. delay: F_(1,215) = 77.28, p < 0.0001). F. Stronger firing at the end of the right return arm in the delay task but not in the continuous task (continuous vs. delay: F_(1,251) = 42.95, p < 0.0001). G–L. Cells that fired as rats traversed different parts of the stem. G. This cell had a higher firing rate when traversing the stem on LR trials in the continuous task, but the difference between continuous and delay tasks was not reliable (F_(1,279) = 2.3, p = 0.13). H. This cell fired robustly in the continuous task on LR trials and less so on RL trials, and fired much less in the delay task (continuous vs. delay: F_(1,779) =57.33, p < 0.0001; LR vs. RL: F_(1,779) = 8.64, p = 0.003). I. This cell fired strongly on both LR and RL trials in the continuous task but did not fire in the delay task (continuous vs. delay: F_(1,599) = 75.3, p < 0.0001). J. In the continuous task, this cell fired more strongly on RL than LR trials and fired less in the delay task (continuous vs. delay: F_(1,1139) = 14.91, p < 0.0001; LR vs. RL X continuous vs. delay: F_(2,1139) = 3.3, p = 0.04). K. A cell that fires more strongly when the rat traverses the stem on RL than LR trials in the continuous task (LR vs. RL: F_(1,279) = 10.39, p = .001), and does not fire in the stem during the delay task (continuous vs. delay F_(1,559) = 19.35, p < 0.0001). Note also a place field of the same cell that fires on the left goal arm similarly on the continuous and delay tasks. L. A cell that fires as the rat traverses the stem in the delay task, more so during RL than LR trials (LR vs. RL: F_(1,259) = 10.252, p = .001), and does not fire in the continuous task (continuous vs. delay: F_(1,519) = 5.06, p = 0.03). M–R. Cells that fired as rats traversed different parts of the goal arms. M–O. Cells that fired differentially in the continuous and delay tasks (M. continuous vs. delay X segment F_(9,129) = 3.38, p = 0.01; N. continuous vs. delay: F_(1,149) = 9.15, p = 0.003;. O. continuous vs. delay: F_(1,149) = 12.65, p < 0.0001). P–R. Cells that fired similarly in the two tasks (P. continuous vs. delay: F_(1,159) = 1.51, p = 0.22; Q. continuous vs. delay: F_(1,129) = 1.0, p = 0.32; R. continuous vs. delay F_1,139 = 0.98, p = 0.32).