Validation of a rodent model of episodic memory

Abstract

Episodic memory consists of representations of specific episodes that happened in the past. Modeling episodic memory in animals requires careful examination of alternative explanations of performance. Putative evidence of episodic-like memory may be based on encoding failure or expectations derived from well-learned semantic rules. In Experiment 1, rats were tested in a radial maze with study and test phases separated by a retention interval. The replenishment of chocolate (at its study-phase location) depended on two factors: time of day (morning vs. afternoon) and the presence or absence of chocolate pellets at the start of the test phase. Because replenishment could not be decoded until the test phase, rats were required to encode the study episode. Success in this task rules out encoding failure. In Experiment 2, two identical mazes in different rooms were used. Chocolate replenishment was trained in one room, and then they were asked to report about a recent event in a different room, where they had no expectation that the memory assessment would occur. Rats successfully answered the unexpected question, ruling out use of expectations derived from well-learned semantic rules. Our behavioral methods for modeling episodic memory may have broad application for assessments of genetic, neuroanatomical, neurochemical, and neurophysiological bases of both episodic memory and memory disorders such as those that occur in Alzheimer's disease.

Fig. 1

Schematic representation of experimental design showing topographical views of the maze. The morning or afternoon was randomly selected for presentation of first helpings of food (encoding phase) and second helpings (memory-assessment phase). The figure shows an example of the accessible arms and flavors in encoding and the corresponding memory-assessment phases that would occur after a 2-min retention interval. The presence or absence of chocolate pellets in the central hub immediately prior to memory assessment was needed to decode the replenishment of chocolate at second helpings. In the replenishment conditions, chocolate replenished at the location that recently delivered chocolate, which was predicted by the presence or absence of food (e.g., presence of chocolate in the central hub immediately prior to second helpings memory assessment in the morning but absence of chocolate in the hub in the afternoon); these contingencies were reversed in the non-replenishment conditions. These conditions were counterbalanced across rats (not shown). For each rat, 1 session (i.e., first helpings, retrieval cue, and second helpings) was conducted per day. The same arms were used to illustrate morning and afternoon sessions in the figure to facilitate inspection of presence and absence of chow and chocolate, but these arms were randomly selected in each session for each rat

Fig. 2

Rats preferentially revisit the chocolate location when it is about to replenish. The probability of a revisit to the chocolate location in the first four choices of a test phase is shown for replenishment and non-replenishment conditions; replenishment and non-replenishment conditions were presented in random order. The presence or absence of food in the hub, immediately prior to memory assessment, served as a cue that could be used to predict the replenishment or non-replenishment of chocolate. Error bars represent 1 SEM. ***p < 0.001 difference between replenishment and non-replenishment conditions

Fig. 3

Rats preferentially revisit the chocolate location when it is about to replenish when the retention interval was approximately 1 h. The probability of a revisit to the chocolate location in the first four choices of a test phase is shown for first replenishment and first non-replenishment conditions. Each condition was tested once, in random order. Error bars represent 1 SEM. **p = 0.009 difference between replenishment and non-replenishment conditions

Fig. 4

a Rats preferentially revisit the chocolate location when it is about to replenish. These data come from the last ten sessions of mixed testing of replenishment and non-replenishment conditions in Maze 1 and are referred to as the mixed baseline. **p = 0.02 difference between replenishment and non-replenishment conditions. b In the chocolate probe, rats revisited the corresponding chocolate location in Maze 2 at a higher rate when chocolate was unexpectedly replenished compared with the non-replenishment mixed baseline in Maze 1 (labeled Replenish and Non-replenish) and designated baseline in Maze 2 (labeled Designated). The probability of revisiting corresponding chocolate location in Maze 2 is labeled Chocolate Probe. The mixed baseline is reproduced from a to facilitate comparison with the chocolate probe. ⁺⁺p = 0.005 difference between chocolate probe and non-replenishment mixed baseline; ^xxxp = 0.001 difference between chocolate probe and designated baseline. c In the sucrose probe, rats revisited the corresponding sucrose location in Maze 2 when sucrose was unexpectedly replenished compared with the non-replenishment mixed baseline in Maze 1 and designated baseline in Maze 2. ⁺p = 0.03 (one-tailed) difference between sucrose probe and non-replenishment mixed baseline; ^xxp = 0.01 difference between sucrose probe and designated baseline. a–c Error bars represent 1 SEM