Distinct roles for dorsal CA3 and CA1 in memory for sequential nonspatial events

Abstract

Previous studies have suggested that dorsal hippocampal areas CA3 and CA1 are both involved in representing sequences of events that compose unique episodes. However, it is uncertain whether the contribution of CA3 is restricted to spatial information, and it is unclear whether CA1 encodes order per se or contributes by an active maintenance of memories of sequential events. Here, we developed a new behavioral task that examines memory for the order of sequential nonspatial events presented as trial-unique odor pairings. When the interval between odors within a studied pair was brief (3 sec), bilateral dorsal CA3 lesions severely disrupted memory for their order, whereas dorsal CA1 lesions did not affect performance. However, when the inter-item interval was extended to 10 sec, CA1 lesions, as well as CA3 lesions, severely disrupted performance. These findings suggest that the role of CA3 in sequence memory is not limited to spatial information, but rather appears to be a fundamental property of CA3 function. In contrast, CA1 becomes involved when memories for events must be held or sequenced over long intervals. Thus, CA3 and CA1 are both involved in memory for sequential nonspatial events that compose unique experiences, and these areas play different roles that are distinguished by the duration of time that must be bridged between key events.

Figure 1.

Test of memory for the order of stimuli in trial-unique odor pairs. At study, animals were presented with 10 odor-paired associates and odors in a pair were presented one at a time. At test, animals were presented with the same 10 odor pairs and were required to distinguish pairs where the odors within a pair were presented in the same order as during study (“old”) from pairs where the odors were presented in the reverse order (“new”). Old and new order test pairs were presented in a pseudorandom order. The first odor in each test pair acted as a cue to the ordering of the odors within a test pair; the animal was required to place its nose over the cup, but no digging response was required or rewarded. When the second cup was presented, the animal could dig to retrieve a reward if the order was new. If the order was old, the animal was required to approach an empty cup in the back of the home cage to obtain reward.

Figure 2.

Reconstruction of lesions to dorsal hippocampal subregions CA3 (top) and CA1 (bottom) at −2.80, −3.80, and −4.30 mm posterior to bregma. Black, smallest lesion; light gray, average lesion across animals; solid line, largest lesion.

Figure 3.

Photomicrographs of coronal sections stained with cresyl violet at approximately −3.48 mm posterior to bregma: (A) sham-operated control; (B) CA3 lesion; (C) CA1 lesion.

Figure 4.

Memory performance in controls and rats with dorsal CA1 or CA3 lesions. (A) Percent correct (± SEM) for each group in sessions prior to surgery. (B) Postoperative performance when the interval between presented odors in a pair was 3 sec at study. Controls and rats with CA1 lesions continued to perform well, whereas rats with CA3 lesions were severely impaired. (C) Performance when the inter-item interval was extended to 10 sec at study. Controls continued to perform well, but rats with CA1 lesions, as well as rats with CA3 lesions, were severely impaired.