Several recent studies have begun to explore the neurobiological basis of serial learning and memory in rats.  They suggest how serial learning processes might be integrated into more general neurobiologically based models of learning and memory.  In one study, Olton, Shapiro, and Hulse (1984) tested rats' sequential memory.  Four quantities of food 14, 7, 1, and 0 pellets of food were placed in the goal boxes at the ends of the four arms of a plus maze.  Rats were allowed to choose freely among the arms and over a period of days learned to choose the large quantities of food first and the smallest quantities of food last.  Thus rats had encoded a stimulus alphabet of four elements and had also learned an orderly response to the four elements as they were distributed in four spatial locations represented by the four goal boxes of the plus maze.  Once rats had learned this task, they were given lesions of the fimbria‑fornix (FFx), the major extrinsic pathway of the hippocampus.  Subsequent testing showed that the rats could remember to search out the quantities in the order in which they had previously learned them.  In other words, rats would go first to 14, then to 7, then to 1, then to the arm containing 0 pellets of food.  However, if before given a free choice in the maze the rats were required to sample one or more of the quantities out of order in a forced choice procedure, they subsequently failed to remember having sampled the quantities when they were tested in the free choice test.  For example, if a rat were allowed to retrieve the 1‑pellet quantity before being given the free choice test, when the rat was allowed to make a free choice among the arms, the rat went first to 14, then to 7, then to 1 just as if it had never sampled the 1‑pellet quantity in the preexposure.  These kinds of mistakes indicated that rats had no memory for previously sampling food quantities from the maze before the free choice.  However, subsequent tests showed that rats could remember elements sampled in preexposure as long as the quantities were received in the order in which they had originally learned them.  For example, if a rat was first preexposed to the arms containing 14 and 7 pellets of food, when given a free choice, the rat would not run down the arms previously containing 14 and 7, but would go immediately to 1 and then 0.  Thus FFx‑lesioned rats could remember elements presented in order, but could not remember elements presented out of the order originally learned.  These results are consistent with Olton et al.’s (1984) interpretation  that the impairment produced by FFx lesions was an impairment of working memory, but not reference memory.  They are also consistent with Eichenbaum et al.’s (1992) idea that hippocampus mediates representational flexibility, the ability to use declarative memories flexibly in new configurations, situations, or tasks.  This idea predicts that FFx-lesioned rats should be inflexible in their use of sequential information learned before surgery, and therefore they should be impaired in their ability to respond to probe situations where patterns differed from the training pattern.  Yet another interpretation of Olton et al.’s (1984) results is consistent with the view that hippocampus mediates item associative processes in SPL, but not rule-induction and memory for pattern structure (Fountain, Schenk, & Annau, 1985).  According to this latter RL view, FFx lesions spare information about pattern structure that mediates responding according to the rule learned in training prior to surgery.

A second experiment shows that hippocampal lesions produce results predicted by the RL view of serial-pattern learning if one views rule-induction as a process potentially dissociable from item association formation.  Fountain, Schenk, and Annau (1985) trained rats with long monotonic and nonmonotonic patterns created from quantities of brain‑stimulation reward.  The monotonic pattern was 18‑10‑6‑3‑1‑0 and the nonmonotonic pattern was 18‑1‑3‑6‑10‑0.  Prior to training, one group of rats was exposed to trimethyltin (TMT), a neurotoxic organometal which produces damage in the limbic system, primarily in the hippocampus.  TMT‑exposed rats learned the formally simple monotonic 18‑10‑6‑3‑1‑0 pattern as fast as control rats, but learned the nonmonotonic 18‑1‑3‑6‑10‑0 pattern slower than controls. 

According to Olton et al.(1984), hippocampal damage should have impaired working memory, but for both groups of rats reference memory should have been intact.  However, the results indicate differential impairment for two different kinds of patterns despite the fact that reference memory should have been intact and available for learning both kinds of patterns.  Similarly, according to Eichenbaum et al. (1992), flexible declarative memory should have been impaired, but inflexible nondeclarative memory should have been spared.  This view suggests that since learning for both groups involved learning to respond to a consistent repeating pattern, learning for both should have been spared following TMT damage to the hippocampus.  The results fit best with the notion that rule-induction processes were spared following TMT damage, whereas item associative processes were impaired by TMT damage.  These, along with other data, suggested that item association formation is a hippocampal-dependent process, whereas rule induction is not.  A dissociation of this sort may be difficult to model with SPAM, though Metcalfe (1993)  has succeeded in simulating characteristics of Korsakoff's amnesia using a closely related model, CHARM.

In a third series of experiments (Fountain & Rowan, 2000), we sought additional evidence for this distinction between item associative and rule induction processes.  In the first study of the series, rats were trained on two patterns, one which was structurally “perfect” and a second virtually identical to the first, but containing a single element that violated the otherwise simple structure.  The Perfect (P) and Violation (V) patterns were:

P Pattern:  123 234 345 456 567 678 781 812

V Pattern:  123 234 345 456 567 678 781 818

As before, the digits indicate the reinforced lever for successive trials.  The last “8” item of the V pattern (underlined) was the violation element.  Rats from one group for each pattern condition were injected with MK-801 daily before training.  MK-801 is a systemically administered NMDA receptor antagonist that blocks neuronal plasticity, known as  long-term potentiation,

in the hippocampus.  It is thought that MK-801 should impair any hippocampal-dependent learning.  As shown in Figure 7, MK-801 had little effect on learning to respond to rule-based items within chunks.  However, it did impair responding at points where rules were violated, namely, on the first trial of each new chunk and, most dramatically, for the violation element.  Although rats showed no signs of learning to respond to the violation element, throughout the experiment they produced rule-based errors on the violation trial by responding “2” instead of “8” at the end of the sequence (Fountain & Rowan, 2000).  The results are strong evidence that hippocampal damage impaired learning the item associations necessary to track violations of pattern structure while sparing the rule induction processes necessary to induce pattern structure and extrapolate the sequence on the violation trial.

In a later study in the same series (Fountain & Rowan, 2000), we examined the role of hippocampus when new serial pattern information is added to old.  Rats were first trained to a high criterion on a pattern consisting of the first 7 chunks of the P pattern above: 123 234 345 456 567 678 781.  After rats learned the pattern, they were transferred to one of two new patterns that contained all elements of the first pattern and an additional chunk of three additional elements.  The three added elements were either structurally consistent with the first pattern (viz., 812), making it structurally “perfect” (P), or they contained a violation (V) of the pattern structure learned in training (viz., 818).  On the day of transfer, half the rats were injected with MK-801 to determine the effects of hippocampal dysfunction on the rats’ ability to integrate structurally consistent or inconsistent new information with an already learned pattern.

As shown in Figure 8, when a structurally consistent chunk was added in the P transfer, the effects of MK-801 were very similar to the effects of the drug on acquisition (Fountain & Rowan, 2000).  That is, the drug produced a selective decrease in the animals' accuracy on the first elements of each chunk of the original pattern, but produced virtually no change in accuracy on the remaining two elements of the 3-element chunks.  The most interesting result occurred when a structurally inconsistent chunk was added in the V transfer.  As shown in Figure 8, although saline controls showed difficulty in learning the new chunk, there was little effect on the rest of the pattern.    However, MK-801 dramatically disrupted performance for elements both in the new chunk to be learned and throughout the rest of the pattern (Fountain & Rowan, 2000).  When this effect is compared to the effects of MK-801 in the P transfer, the effect can only be accounted for by the addition of the terminal violation element.  One interpretation of these results is that adding new information to a pattern representation is possible under MK-801, but only if the information is consistent with pattern structure that has already been encoded.  In fact, this initial evidence indicates that for rats with hippocampal impairment, new information that is structurally inconsistent can disrupt previously well-learned response patterns.  This suggests that, in intact animals, nonhippocampal systems mediate rule induction whereas hippocampus may play a role in the successful integration of new rule-inconsistent SPL information with already   encoded   information  about  pattern  structure.     These  ideas  are reminiscent of the distinction between flexible and inflexible memory processes proposed by Eichenbaum et al.(1992), but our MK-801 results suggest that what constitutes “representational flexibility” is far from resolved.  Under MK-801, rats were able to add a rule-consistent chunk to their already learned pattern with relatively little difficulty, but not a rule-inconsistent chunk.

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