Context preexposure prevents forgetting of a contextual fear memory: implication for regional changes in brain activation patterns associated with recent and remote memory tests

Contextual fear conditioning was maintained over a 15-day retention interval suggesting no forgetting of the conditioning experience. However, a more subtle generalization test revealed that, as the retention interval increased, rats showed enhanced generalized fear to an altered context. Preexposure to the training context prior to conditioning, however, prevented this enhanced generalized fear from developing. These results support the hypothesis that the memory representation of the context degrades as the memory ages and is responsible for enhanced generalization. The implications of these results for systems consolidation versus forgetting interpretations of regional changes in neural activation patterns that occur as memories age are discussed.     

The effects of cholinergic drugs upon recognition memory in rats

This study measured the effects of the muscarinic blocker, scopolamine, upon object recognition. In order to test object recognition, rats were trained to choose between two distinctive goal boxes, one of which was familiar, and the other was novel. Selection of the unfamiliar goal box was always rewarded (nonmatching-to-sample), and new pairs of start/goal boxes were used on every trial.

In the first experiment it was found that injections of 0.05 mg/kg scopolamine hydrochloride and above produced significant impairments on this nonspatial test of working memory. A second experiment examined whether scopolamine caused a loss of retention by comparing the effects of the drug when the interval between stimulus presentation and choice test was increased from just over 0 sec to 60 sec. While the highest dose of scopolamine hydrobromide (0.06 mg/kg) was sufficient to produce a significant impairment on the longer retention interval, there was no evidence that this dose produced faster forgetting of the stimuli. This result suggests that the drug caused a general depression in performance, which may or may not reflect amnesic properties. In contrast, simultaneous tests with the anticholinesterase, physostigmine, indicated that increasing available acetyl choline might attenuate the effects of the retention intervals. A final series of control tests revealed that the rats relied on cues from a variety of sensory modalities in order to perform the nonmatching task.     

GABA(A) receptors determine the temporal dynamics of memory retention

Four experiments studied the role of GABA(A) receptors in the temporal dynamics of memory retention. Memory for an active avoidance response was a nonmonotonic function of the retention interval. When rats were tested shortly (2 min) or some time (24 h) after training, retention was excellent, but when they were tested at intermediate intervals (1-4 h), retention was poor. Activity at GABA(A) receptors was critical for impairing memory retention at the intermediate intervals because injection of the GABA(A) receptor partial inverse agonist FG7142 prior to test significantly improved performance. These retention enhancing effects of FG7142 were dose-dependent and not due to any nonspecific effects of FG7142 on activity. Our results suggest that the temporal dynamics of memory retention may be caused by variations in neurotransmission through the GABA(A) receptor in the post-training period.     

Short-term memory for temporal intervals: Contrasting explanations of the choose-short effect in pigeons

To better understand short-term memory for temporal intervals, we re-examined the choose-short effect. In Experiment 1, to contrast the predictions of two models of this effect, the subjective shortening and the coding models, pigeons were exposed to a delayed matching-to-sample task with three sample durations (2, 6 and 18 s) and retention intervals ranging from 0 to 20 s. Consistent with the coding model, the results suggested a sudden forgetting of memories for duration. In Experiment 2, to test the confusion hypothesis, the characteristics of the ITI and the retention interval differed. Contrary to the confusion hypothesis, a choose-short effect was obtained. In both experiments, a test with only two of the three comparison keys was performed. The results suggest three effects that may be controlling the birds’ responses: stimulus generalization when no retention interval is present; an increase in random responding at longer retention intervals; and, similarly, an increase in preference for the “short-sample” key at longer retention intervals.     

Stimulus generalization of conditioned taste aversion in rats

Relatively little information is available regarding the intradimensional stimulus generalization of conditioned taste aversion (CTA). Experiment 1 employed a between-groups generalization test to examine the extent to which conditioned flavor aversion to one sucrose solution generalized to other concentrations of sucrose in adult rats. Evidence of a gradient of aversion was obtained. Because generalization gradients in other tasks have been found to flatten over a retention interval, Experiment 2 investigated the effects of delayed testing (2, 7, or 21 days) upon the slope of the generalization gradient. The generalization gradient flattened at the intervals, suggesting that subjects forgot the specific attributes of the conditioning concentration and avoided generalized stimuli as if they were the original CS. Experiment 3 used a long delay between taste and toxicosis to degrade the associative contingency and found no evidence that the generalization gradients found in the first two experiments could be explained in terms of enhanced neophobia due to poisoning. These findings provide further evidence (cf. A. W. Logue, 1979, Psychological Bulletin, 86, 276-296; M. Domjan, 1980, in J. S. Rosenblatt, R. A. Hinde, C. Beer, & M. Busnel (Eds.), Advances in the study of behavior, Vol. 11, New York: Academic Press) that CTA shares a number of similarities with other learning processes. Further, they illustrate that stimulus forgetting can be detected in a paradigm considered relatively immune to retention loss.     

Ontogeny of early event memory: II. Encoding and retrieval by 2- and 3-month-olds

The ability of 2-month-old infants to discriminate changes in a 5-object crib mobile following a retention interval of 24 hr was assessed using the mobile conjugate reinforcement paradigm. Infants were trained in 3 daily 15-min sessions to produce mobile movement by footkicking. Twenty-four hr later, independent groups received generalization tests with mobiles containing 1–5 novel objects substituted into their original training mobile. A control group was tested with the original training mobile. These findings were compared with findings of 2 previous studies involving identical procedures with 3-month-olds, reanalyzed for measures of individual performance over successive test minutes. Although, in absolute terms, 2-month-olds had a flat generalization gradient relative to 3-month-olds, when each infant's kick rate during the generalization test was expressed relative to that infant's kick rate before, and at the end of, training, it was found that the generalization gradients of 2- and 3-month-olds were indistinguishable. The relative response measures indicated a surprising degree of specificity by both age groups: Test mobiles containing more than 1 novel object did not cue retrieval, but test mobiles containing no more than 1 new object yielded perfect retention and complete generalization. These data indicate that infants as young as 2 months are capable of encoding and maintaining a representation of the specific details of their training context for at least 24 hr and, after that delay, can perform fine discriminations based on the discrepancy between their test context and that representation.     

Age differences in retention of fixed-interval responding: memory or habitation effects?

Long-term retention of fixed-interval curvature as an index of recall memory which is relatively free of retrieval cues was examined in younger and older rats. Previous research on free-operant behavior in younger and older rats showing within-session decrements in behavior of older rats and within-session increments in younger rats suggested that the results of recall memory tests would depend upon the duration of the test session and the point within the session where data were collected. Consistent with such expectations, recall of fixed-interval curvature was poorer in older rats when data from late in the test session or data averaged over the entire 45-min session were used, but the opposite finding, numerically better retention in the older rats, occurred when data from the earliest part of the test session were used. The results suggest that age-related performance differences from which age-related memory differences are inferred may be confounded by other age-related effects upon performance which have nothing to do with memory.     

Impaired Visuospatial Short-Term Memory in Children with ADHD

Previous studies provide clear evidence that visuospatial memory performance in children with attention-deficit/hyperactivity disorder (ADHD) is significantly lower than in typically developing children. In the present study, we investigated a major cause of their low performance using a spatial span test. Possibly, inattention resulting from lack of motivation or interest causes their low performance so that they do not correctly encode targets to be remembered. On the other hand, a deficit in temporary maintenance per se may cause their low performance; that is, their inefficient use of rehearsal during a retention interval may lead to memory traces’ fast decay. Results in this study indicated that children with ADHD could sustain attention during the encoding phase. Furthermore, their performance at delayed recall was significantly lower than immediate recall, but delayed recall did not affect typically developing children's performance. These results provide evidence for the likelihood that a factor causing children with ADHD difficulty in temporarily maintaining visuospatial information is fast decay of memory traces as a result of inefficient use of rehearsal, not inattention in the encoding phase.     

Effect of novel experiences on retention of inhibitory avoidance behavior in mice: the influence of previous exposure to the same or another experience

Mice were trained and tested in a step-through inhibitory avoidance task with a 24-h interval between training and testing. At one of several intervals prior to the test session (9 h, 6 h, 3 h, or 6 min), they were given one of the following novel experiences: 4 min in a small Plexiglas box containing an empty water bottle, or 4 min hanging from the wire mesh ceiling of a large Plexiglas box. When given 3 h or 6 min before testing, both novel experiences enhanced retention test performance. The effect was antagonized by naltrexone and mimicked by an administration of beta-endorphin 6 min prior to testing. Thus, the findings are consistent with previous evidence suggesting that the effects of novel experiences on retention test performance are due to an activation of the brain beta-endorphin system. When one of the novel experiences given 3 h or 6 min prior to testing was preceded by the same experience given 6 h earlier retention test performance was not enhanced. Thus, the enhancing effect is obtained only if the experience is novel. Further, an experience given prior to retention testing did not affect performance if either the same or a different experience was given 3 h earlier. This finding is consistent with previous evidence indicating that following a novel experience, the brain beta-endorphin remains unresponsive for several hours. These results provide additional evidence that novel experiences prior to retention testing affect retention performance and provide additional support for the view that the effect may involve the release of beta-endorphin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spared anterograde memory for shock-probe fear conditioning after inactivation of the amygdala

Previous studies have shown that amygdala lesions impair avoidance of an electrified probe. This finding has been interpreted as indicating that amygdala lesions reduce fear. It is unclear, however, whether amygdala-lesioned rats learn that the probe is associated with shock. If the lesions prevent the formation of this association, then pretraining reversible inactivation of the amygdala should impair both acquisition and retention performance. To test this hypothesis, the amygdala was inactivated (tetrodotoxin; TTX; 1 ng/side) before a shock-probe acquisition session, and retention was tested 4 d later. The data indicated that, compared with rats infused with vehicle, rats infused with TTX received more shocks during the acquisition session, but more importantly, were not impaired on the retention test. In Experiment 2, we assessed whether the spared memory on the retention test was caused by overtraining during acquisition. We used the same procedure as in Experiment 1, with the exception that the number of shocks the rats received during the acquisition session was limited to four. Again the data indicated that amygdala inactivation did not impair performance on the retention test. These results indicate that amygdala inactivation does not prevent the formation of an association between the shock and the probe and that shock-probe deficits during acquisition likely reflect the amygdala's involvement in other processes.     

Support for a theory of memory for event duration must distinguish between test-trial ambiguity and actual memory loss

Staddon and Higa's (1999) trace-strength theory of timing and memory for event duration can account for pigeons' bias to "choose short" when retention intervals are introduced and to "choose long" when, following training with a fixed retention interval, retention intervals are shortened. However, it does not account for the failure of pigeons to choose short when the intertrial interval is distinct from the retention interval. That finding suggests that stimulus generalization (or ambiguity) between the intertrial interval and the retention interval may result in an effect that has been attributed to memory loss. Such artifacts must be eliminated before a theory of memory for event duration can be adequately tested.     

Sequential variables and the Kamin effect

The results of two experiments demonstrated that retention deficits occurred in a within-subjects design only when the intermediate interval test was either the first or second test of the retention of prior aversive conditioning experience; when two relearning tests preceded a 1-hr test, no performance deficits were observed. It was suggested that internal cues may serve as memory attributes of avoidance behavior during early stages of avoidance learning, while other stimuli may facilitate the retrieval of the memory of prior avoidance training with repeated testing.     

Spatial memory in rats after 25 hours

We investigated the time course of spatial-memory decay in rats using an eight-arm radial maze. It is well established that performance remains high with retention intervals as long as 4 h, but declines to chance with a 24-h retention interval (Beatty, W. W., & Shavalia, D. A. (1980b). Spatial memory in rats: time course of working memory and effect of anesthetics. Behavioral & Neural Biology, 28, 454-462). It is possible that 24 h reflects a genuine retention limitation of rat spatial memory. Alternatively, it may be possible to identify factors that might support memory performance even after very long delays. The current experiment was conducted to test the above two hypotheses. We evaluated performance using two intertrial intervals (24 and 48 h) and two retention intervals (1 and 25 h). Increasing the intertrial interval produced an approximately constant increase in performance for both retention intervals. This improvement is consistent with a trial-spacing effect (i.e., the superiority of spaced over massed trials). Rat spatial memory apparently lasts at least 25 h.     

Visual long-term memory for spatial frequency?

It has been suggested that a visual long-term memory based on a sensory representation of the stimulus accounts for discrimination performance when the reference and the test stimuli are separated in time. Decision processes involved in setting response criteria, however, may also contribute to discrimination performance. In the present study, it is shown that under proper control, spatial frequency discrimination thresholds from a group of observers, each performing on a single trial, are significantly higher for a 2-h than for a 5-sec retention interval, whereas thresholds from individual observers performing in repeated trials with a 2-h retention interval are considerably lower. The results suggest that discrimination performance may depend on the retention of task-relevant information, such as a response criterion, rather than on visual memory of the stimulus. It is concluded that it is risky to postulate ahigh-fidelity long-term visual memory for spatial frequency on the basis of psychophysical group discrimination thresholds.     

Acquisition and retention of a letter-detection skill

In two experiments, we examined the acquisition and retention of a letter-detection skill with a consistent-mapping procedure. In Experiment 1, subjects were trained from 0 to 4 sessions at detecting the letter H in displays containing random letters, and retesting occurred after a 1-month delay. Performance improved and in some cases became more automatic, and the performance level was maintained over the retention interval. When tested with a prose passage, the high error rate on the word THE was eliminated after training and after the retention interval, regardless of the amount of training. In Experiment 2, two subjects were given 12 sessions of training followed by a retention test 6 months later. For 1 subject there was also a retention test 15 months after acquisition. Performance improved dramatically with training, and substantial but not complete automaticity was achieved. Performance on the retention tests was close to the final acquisition level. The surprising lack of forgetting in this study was contrasted with the substantial forgetting typically found in studies of verbal learning.     

Time-dependent effects of post-trial amphetamine treatment in rats: evidence for enhanced storage of representational memory

Two studies were conducted to test the ability of post-trial amphetamine treatment to improve later recall in a nonaversively motivated task. These studies utilized 8- and 12-arm radial mazes, respectively, with an 11-h retention interval imposed after the rat traversed half the arms of the maze (termed, the to-be-remembered-event, or TBRE). In Experiment 1, the rats were injected with amphetamine (0, .25, and .50 mg/kg) immediately after the TBRE. Because the drug treatment improved retention, a time dependency study was conducted in which the drug (0 and .33 mg/kg) was administered 0, 3, and 6 h after the TBRE. The finding that amphetamine injection at 0, but not 3, h post-trial improved later recall indicates that the benefit derived from the former treatment is not due to proactive influences at the time of the retention test. Drug treatment 6 h post-trial produced a borderline improvement of recall; possible mechanisms are discussed. Two conclusions can be drawn from these results: (1) amphetamine administration can improve recall under conditions in which this effect cannot be attributed to alterations in information processing during either the learning or the retention sessions, indicating that the drug modulates memory storage processes; and (2) amphetamine treatment can improve working memory, thus excluding an alternative interpretation for the previous reports of impaired short-term memory in animals, all of which entailed assessments of working memory. The possibility remains, however, that the impairment seen in these tasks reflects the requirement for erasure of information from previous trials within each daily session, rather than the duration of the retention interval.     

Exposure to a retrieval cue in rats induces changes in regional brain glucose metabolism in the amygdala and other related brain structures

Pre-test exposure to training-related cues is known to improve subsequent retention performance. To identify brain regions engaged in processes promoted by retrieval cues, a brain imaging approach using the [6-14C]glucose autoradiographic technique was used. Sprague-Dawley rats trained in a brightness discrimination avoidance task were submitted to different cueing conditions after a 1- or a 21-day training-to-test interval (TTI). Animals were either non-cued, cued with a box, or cued with a box and the light that served as a discriminative stimulus. Effects of the different cueing conditions on retention performance or on metabolic activity in 58 different brain regions were investigated. Rats cued with the light exhibited a subsequent improvement of their retention performance relative to controls, when tested at the 1- but not 21-days TTI, confirming our previous results. At the 1-day retention interval, a comparison between rats cued with the box and rats cued with the box and the light showed that the light cue significantly increased glucose uptake in a neuronal network composed of the lateral, basal, and central nuclei of the amygdala, the anterior and suprachiasmatic hypothalamic nuclei, the nucleus accumbens, the medial septum, and the insular cortex. In contrast, at the 21-day retention interval, both groups demonstrated similar cerebral metabolic activity. The present results indicate that exposure to a light cue increased metabolic activity in the previously mentioned brain structures only when the light acted as an effective retrieval cue, suggesting an involvement of this network in the processes triggered by a retrieval cue. Arguments are provided supporting the notion that the amygdala may play a key role in these processes. Whether the amygdala is a part of a neural network involved in retrieval processes or in neuromodulating systems that favour the efficacy of retrieval processes is also discussed.     

Acquisition and retention of active avoidance behavior in previsual rats

The ability of previsual rats to acquire and retain an active avoidance response at intervals ranging from 0 min to 48 hr was examined in five experiments. Experiments 1 and 2 demonstrated that improvement in avoidance responding over trials was a training effect. Experiments 3 and 4 demonstrated that there was no evidence of retention of the avoidance response over retention intervals ranging from 15 min to 48 hr. Testing at intervals of 0-30 min in Experiment 5 indicated that 10-day-old rats could retain the response over intervals ranging from 0-15 min, but not over a 30-min interval. However, even at the very short intervals (5-15 min), there was evidence of a retention deficit. In general, the results suggest that previsual rats have sufficient memory capabilities to acquire an active avoidance response and to retain it over a 15-min interval. However, without intervention, e.g., reactivation, a retention deficit appears almost immediately, and retention loss seems complete within 30 min. This procedure and phenomenon may prove useful in allowing an immediate assessment of variables believed to alleviate retention loss and in eliminating the influence of many extraneous variables that could alter the retention performance of developing animals.     

The effects of pretraining and reminder treatments on retrograde amnesia in rats: comparison of lesions to the fornix or perirhinal and entorhinal cortices

The present experiment examined the effects of pretraining and reminder treatments on the retention of a nonrelational odor-guided digging task following lesions to the hippocampal formation (i.e., fornix) or parahippocampal region (i.e., perirhinal and entorhinal cortices). The results showed that fornix-lesioned rats and control rats had good retention of the task and did not differ from each other; however, perirhinal- and entorhinal-lesioned rats were severely impaired and differed from fornix and control rats. The present experiment found no attenuation of amnesia following pretraining, which may be due to the lesion technique employed and the size of the resulting lesions. However, the experiment found a significant difference in performance following a reminder treatment, even in the severely impaired perirhinal- and entorhinal-lesioned group.     

Retention interval and intertrial interval in a serial learning or delayed discrimination task

In each of four experiments, rats were provided with the same three-event decreasing series (18-1-0) of 0.045-g food pellets in a runway. Tracking, running fast to 18 pellets and running slow to 1 and 0 pellets, was investigated as a function of the temporal interval elapsing between the events of the series (the retention interval), shifts in retention interval, and number of trials each day (or the intertrial interval), a trial being defined as presentation of each of the three events of the series. Neither retention interval, which varied from 15 s to 30 min in various investigations, nor shifts in retention interval affected tracking when only one trial was given each day. But when more than one daily trial was given, tracking was acquired more slowly and was disrupted by a shift in retention interval from 15 s to 5 min. Tracking was also disrupted by a shift from one to two trials each day. These results indicate that when given one 18-1-0 trial each day, the rat partitions events on a first-event/subsequent-event basis; that little forgetting occurs even at long retention intervals; that somewhat different memories signal events when one or more than one 18-1-0 trial occurs each day; and that retention interval deficits can arise owing to the same or similar memories' signaling different events. The results described limit the generality of three hypotheses suggested in two recent investigations: that as retention interval increases, rats find it increasingly difficult to remember and utilize serial position cues; that tracking in serial tasks is not influenced by number of trials each day; and that there are specific stimuli associated with each retention interval which, when changed, necessarily disrupt performance.