The hippocampus and disambiguation of overlapping sequences

Abstract

Recent models of hippocampal function emphasize its potential role in disambiguating sequences of events that compose distinct episodic memories. In this study, rats were trained to distinguish two overlapping sequences of odor choices. The capacity to disambiguate the sequences was measured by the critical odor choice after the overlapping elements of the sequences. When the sequences were presented in rapid alternation, damage to the hippocampus, produced either by infusions of the neurotoxin ibotenic acid or by radiofrequency current, produced a severe deficit, although animals with radiofrequency lesions relearned the task. When the sequences were presented spaced apart and in random order, animals with radiofrequency hippocampal lesions could perform the task. However, they failed when a memory delay was imposed before the critical choice. These findings support the hypothesis that the hippocampus is involved in representing sequences of nonspatial events, particularly when interference between the sequences is high or when animals must remember across a substantial delay preceding items in a current sequence.

Fig. 1.

The odor sequence task. a, The two odor sequences are indicated by letters. In performing each sequence, the rat selected between vertically aligned odors in each sequence; in both sequences, X was to be selected overW, and Y over Z.b, Illustration of an example trial on sequence 1. The location where the odors are presented is randomly determined. On the first four pairs (P1–P4) and pair 6 (P6), the animal was required to lift the perforated lid and dig from the cup containing the reward; the lid of the alternative choices was “locked.” On pair 5 (P5), no lids are used, and the first choice is scored. +, Reinforced odor.

Fig. 2.

Reconstructions of the smallest and largest hippocampal lesions. Coronal sections are adapted from Swanson (1992).Light gray refers to the largest volume of hippocampus damaged; dark gray indicates smallest lesion.

Fig. 3.

Performance (mean ± SE) of control rats and rats with ibotenic acid (IBO) hippocampal lesions on pair 5 (P5) and pair 6 (P6) tests. *p < 0.025.

Fig. 4.

Performance (mean ± SE) on pair 5 judgements by control rats and rats with ibotenic acid (IBO) hippocampal lesions on the first and second five-session blocks of postoperative sessions. *p < 0.025.

Fig. 5.

Performance (mean ± SE) of control rats and rats with radiofrequency (RF) hippocampal lesions on preoperative and postoperative pair 5 testing. The postoperative performance is divided into two blocks of five sessions. *p < 0.025.

Fig. 6.

Performance (mean ± SE) of control rats and rats with ibotenic acid (IBO) or radiofrequency (RF) hippocampal lesions on postoperative pair 5 choices. Data are shown in two blocks of five sessions. The normalized scores were obtained by subtracting the preoperative performance level from the performance on each postoperative block. Note that a negative score indicates a decrease in performance from the preoperative level. *p < 0.025.

Fig. 7.

Performance (mean ± SE) of control rats and rats with radiofrequency hippocampal lesions on preoperative and postoperative pair 5 choices in the random-presentation version of the sequence disambiguation task. Scores are shown for the final stage of preoperative training and in postoperative testing with minimal and 30 min delay before presentation of pair 5. *p < 0.025.