Differential effectiveness of various prior-cuing treatments in the reactivation and maintenance of memory

In 3 experiments, changes were examined in the characteristics of newly acquired and reinstated memories over time in preweanling rats. Experiment 1 indicated that forgetting after conditioning was monotonic, with the upper limit of retention at approximately 120 min posttraining. In Experiment 2, Ss were exposed to various elements of the training episode before testing, after either a 3- or a 24-hr retention interval. The results indicated that the prior-cuing treatments were differentially effective and that the effectiveness of a reactivation treatment may change as a function of the retention interval. Experiment 3 indicated that Ss expressed a conditioned aversion at much longer intervals following reactivation treatments than after initial conditioning. Furthermore the susceptibility of the reinstated memory to forgetting was dependent on the prior-cuing treatment used. The results suggest a change in the memorial representation of the conditioning episode over time.     

Stimulus and procedural determinants of the forgetting of conditioned fear.

Two studies investigated factors believed to influence the retention of acquired fear in rats. The results show clearly that the lack of forgetting over 24-hr interval reported by previous investigators is due to a depression of performance on the immediate test (3-min retention interval) resulting from the procedure of not handling the rats during conditioning but then handling them on every trial during the retention test. In accord with the McAllister's interpretation of related results, the depression of performance after short retention intervals may be due to a lack of generalization from training to the testing situation. As the retention interval is lengthened, the amount of generalization increases and escape performance improves on a relative basis. The nature of the retention function may be severely distorted by selection of an inappropriate paradigm for its evaluation.     

Time-dependent changes in inaccessible memory

The present experiment examined whether forgetting of contextual attributes—the loss of discriminability of background stimulus features over time—also occurs when a memory remains inaccessible (amnestic) during the retention interval. To examine this issue, rats received an acute hypothermia treatment that caused reversible anterograde amnesia for a passive-avoidance task and were tested 1 or 7 days later in either the same or a different context. At the short retention interval, the subjects discriminated between the contexts, as evidenced by the finding that reversal of amnesia occurred only in the training context. However, at the 7-day interval, recovery of the avoidance response was induced in either context, reflecting the forgetting of differentiating characteristics. These findings indicate that inaccessible memory remains susceptible to processes of modification and distortion that typically influence intact memories.     

The temporal dynamics of retention of a context memory: something is missing

We use a variation of contextual fear conditioning, called the context pre-exposure facilitation effect (CPFE) to study the rat's memory for context. In this paradigm, the rat is pre-exposed to a conditioning context and later returned to that context, where it is immediately shocked. The memory context is revealed by the fact that pre-exposure to the conditioning context, but not to a different context, greatly enhances conditioned fear produced by immediate shock. We report that rat's retention of the context memory is a nonmonotonic U-shaped function of the interval separating pre-exposure and immediate shock. Retention performance decays rapidly so that within 2 min of pre-exposure there is no evidence that the rat was pre-exposed to the context. Within a few hours, however, a strong CPFE was observed that persisted for at least 28 d. Two hypotheses are discussed: (1) the descending arm of the U represents a retrieval failure, and (2) the U-shaped function represents two discontinuous memory processes initiated in parallel-short-term synaptic changes that are rapidly initiated, but also decay rapidly, and long-term synaptic processes that take time to generate but can endure for days.     

Time-dependent forgetting in visual short-term memory

ABSTRACT

Whether visual short-term memory can be lost over an unfilled delay, in line with time-dependent forgetting, is controversial and prior work has yielded mixed results. The present study explored time-dependent forgetting in visual short-term memory in relation to other factors. In three experiments, participants compared single target and probe objects over a 2 s or 10 s retention interval. The objects across trials were either similar or dissimilar (Experiment 1) and had to be remembered in the presence of an additional distractor (Experiment 2) or under conditions where the amount of time separating trials varied (Experiment 3). In all experiments, the retention interval manipulation made the biggest contribution to performance, with accuracy decreasing as the retention interval was lengthened from 2 s to 10 s. These results pose problems for interference and temporal distinctiveness models of memory but are compatible with temporal forgetting mechanisms such as decay.     

The Influence of Retention Interval on the US Preexposure Effect: Changes in Contextual Blocking over Time

A number of studies manipulating the length of the interval between conditioning and testing indicate spontaneous recovery from overshadowing, suggesting that certain instances of overshadowing represent a deficit in memory retrieval rather than a failure of animals to form an association between the overshadowed stimulus and the US. The present series of experiments examined the influence of lengthening the retention interval on blocking, another stimulus selection phenomenon that is typically interpreted as an acquisition deficit. The results indicated that when subjects were tested shortly (3 days) after training conditioning to a taste blocked subsequent conditioning to an odor conditioned in compound with that taste (Experiment 1), whereas prior conditioning to an odor did not block subsequent conditioning to a taste conditioned in compound with that odor (Experiment 2). This pattern of results was essentially unchanged when testing occurred at a longer (21-day) retention interval. However, there was evidence of a US preexposure effect in Experiment 2 when subjects in the US ONLY control condition were tested at the 3-day retention interval, but not when testing occurred 21 days after conditioning. Experiments 3 and 4 examined whether this loss of the US preexposure effect over time might actually represent a change in the degree of contextual blocking as the retention interval is lengthened. Exposure to the conditioning context either during the interval between Phase 1 and Phase 2 of conditioning (Experiment 3) or prior to Phase 1 of conditioning (Experiment 4) alleviated this US preexposure effect suggesting that the loss of the US preexposure effect as the retention interval is lengthened observed in Experiment 2 is due to changes in the degree of blocking by contextual stimuli over time. The results are discussed in terms of differential susceptibility of forgetting of two functional roles played by a contextual stimuli in the current situation-context as a CS and context as a retrieval cue for other CS-US associations.     

Increasing CREB in the auditory thalamus enhances memory and generalization of auditory conditioned fear

Although the lateral nucleus of the amygdala (LA) is essential for conditioned auditory fear memory, an emerging theme is that plasticity in multiple brain regions contributes to fear memory formation. The LA receives direct projections from the auditory thalamus, specifically the medial division of the medial geniculate nucleus (MGm) and adjacent posterior intralaminar nucleus (PIN). While traditionally viewed as a simple relay structure, mounting evidence implicates the thalamus in diverse cognitive processes. We investigated the role of plasticity in the MGm/PIN in auditory fear memory. First we found that auditory fear conditioning (but not control manipulations) increased the levels of activated CREB in both the MGm and PIN. Next, using viral vectors, we showed that exogenously increasing CREB in this region specifically enhanced formation of an auditory conditioned fear memory without affecting expression of an auditory fear memory, formation of a contextual fear memory, or basic auditory processing. Interestingly, mice with increased CREB levels in the MGm/PIN also showed broad auditory fear generalization (in contrast to control mice, they exhibited fear responses to tones of other frequencies). Together, these results implicate CREB-mediated plasticity in the MGm/PIN in both the formation and generalization of conditioned auditory fear memory. Not only do these findings refine our knowledge of the circuitry underlying fear memory but they also provide novel insights into the neural substrates that govern the degree to which acquired fear of a tone generalizes to other tones.     

Distributed learning enhances relational memory consolidation

It has long been known that distributed learning (DL) provides a mnemonic advantage over massed learning (ML). However, the underlying mechanisms that drive this robust mnemonic effect remain largely unknown. In two experiments, we show that DL across a 24 hr interval does not enhance immediate memory performance but instead slows the rate of forgetting relative to ML. Furthermore, we demonstrate that this savings in forgetting is specific to relational, but not item, memory. In the context of extant theories and knowledge of memory consolidation, these results suggest that an important mechanism underlying the mnemonic benefit of DL is enhanced memory consolidation. We speculate that synaptic strengthening mechanisms supporting long-term memory consolidation may be differentially mediated by the spacing of memory reactivation. These findings have broad implications for the scientific study of episodic memory consolidation and, more generally, for educational curriculum development and policy.     

Late expression of brain-derived neurotrophic factor in the amygdala is required for persistence of fear memory

In many instances, increase in neuronal activity can induce biphasic secretion of a modulator. The initial release of the modulator triggers the induction of synaptic plasticity, whereas the second-phase release reinforces the efficacy of synaptic transmission and growth of dendrites and axons. In this study, we showed that fear conditioning not only induced the first but also a second peak of brain-derived neurotrophic factor (BDNF) expression. Fluorescent immunohistostaining confirmed that BDNF expression increased at 1 and 12 h after conditioning and returned to baseline at 30 h after conditioning. Mature BDNF expression increased in a similar manner. TrkB-IgG or K252a infusion before training impaired fear memory on days 1 and 7 after training. In contrast, TrkB-IgG or K252a infusion 9 h after fear conditioning did not affect memory retention on day 1 after training but impaired fear memory on day 7 after training. Fear conditioning significantly enhanced Zif268 expression in the amygdala at 12 h after training; this enhanced expression was completely inhibited by TrkB-IgG infusion 9 h after training. The level of growth-associated protein 43 (GAP-43), a marker of newly formed synapses, in the amygdala increased 7 days after fear conditioning. Moreover, conditioned rats had higher AMPA/NMDA ratio than unpaired rats. These results suggest that consolidated memory could be continuously modulated by previous molecular changes produced during memory acquisition.     

Secondary memory and very rapid forgetting

Studies of recall in the absence of expectancy (e.g., Muter, 1980) have suggested that forgetting from primary memory is much more rapid than previously assumed. Two experiments examined the role of secondary memory, as reflected by encoding strategies, in determining this rate of forgetting. Experiment 1 demonstrated that the type of encoding specified by orienting tasks can influence recall in a traditional Brown-Peterson task. Experiment 2 demonstrated a similar pattern of effects of orienting task in the Muter task when recall was not expected, despite much more rapid forgetting. The type of encoding engaged by the orienting tasks did not account for Muter's results. Expectancy and orienting task appear to have separable influences on resource allocation during encoding. The presence of secondary memory influences at even the shortest retention interval indicates that forgetting from primary memory may be even more rapid than has been proposed.     

Effects of Age on the Generalization and Incubation of Memory in the F344 Rat

Freezing (immobility) in the presence of aversive stimuli is a species-specific behavior that is used as an operational measure of fear. Conditioning of this response to discrete sensory stimuli and environmental context cues has been used as a tool to study the neuropsychology of memory dynamics and their development over the lifespan. Three age groups of F344 rats (3, 9, and 27 month) received tone–foot shock pairing (or tone only) in a distinctive chamber on two consecutive days. Separate subgroups of rats from each age group were then tested, at retention intervals of 1, 20, 40, or 60 days, for context-mediated fear in the environment in which they were trained, for generalization of the fear response to a novel chamber, and for fear of the tone. Beginning at day 20, the 27-month-old rats exhibited less freezing behavior than did younger rats when tested in the conditioning context. This age difference was a result of freezing behavior becoming progressively stronger with time in the two younger age groups, a phenomenon that has been referred to as memory incubation. Incubation of the contextual fear response was not detected in the old rats. In a novel context, all age groups exhibited significantly more freezing than did control animals. There was also pronounced incubation of this generalized freezing response, and the extent of incubation declined significantly with age. In the novel context, the freezing response to the tone was robust in all age groups and increased over time, in constant proportion to the degree of freezing elicited by the novel context itself, prior to tone onset. The fact that old animals are known to be relatively selectively impaired in forms of memory that depend on a functional hippocampus suggests a possible explanation for the reduced incubation effects seen in old rats; however, whether the increased expression of fear over time is mediated by a hippocampal-dependent memory consolidation process or whether it reflects a generalized increase in the gain of the circuitry mediating the fear response itself, remains to be determined.     

Differential roles of the basolateral amygdala and nucleus basalis magnocellularis during post-reactivation contextual fear conditioning reconsolidation in rats

The roles of the basolateral amygdala and nucleus basalis magnocellularis in fear conditioning reconsolidation were investigated by means of tetrodotoxin bilateral inactivation performed 96 h after conditioning, immediately after reactivation training. Footshocks of 1.2 mA intensity were employed to induce the generalization phenomenon. Basolateral amygdala inactivation disrupts the contextual fear response and its generalization but not acoustic CS trace retention, when measured 72 and 96 h after tetrodotoxin administration. Nucleus basalis magnocellularis functional inactivation does not affect memory post-reactivation phase of any of the three conditioned fear responses. The present findings show a differential role of the two structures in fear memory reconsolidation and can be a starting point for future investigation of the neural circuits subserving generalization.     

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.     

Rapid reacquisition of fear to a completely extinguished context is replaced by transient impairment with additional extinction training

A series of experiments studied reacquisition of fear reactions to a completely extinguished context. Reacquisition was rapid when reconditioning occurred as soon as the fear reactions were completely extinguished, showing that the original conditioning was intact. However, when reconditioning occurred after massive extinction training, fear reactions were depressed but then recovered across a long retention interval. This recovery was due to reconditioning and was similar to that produced by conditioning a massively preexposed context. These results show that massive extinction converts a potentially dangerous context into one that is merely familiar.     

Encoding, consolidation, and retrieval of contextual memory: differential involvement of dorsal CA3 and CA1 hippocampal subregions

Studies on human and animals shed light on the unique hippocampus contributions to relational memory. However, the particular role of each hippocampal subregion in memory processing is still not clear. Hippocampal computational models and theories have emphasized a unique function in memory for each hippocampal subregion, with the CA3 area acting as an autoassociative memory network and the CA1 area as a critical output structure. In order to understand the respective roles of the CA3- and CA1-hippocampal areas in the formation of contextual memory, we studied the effects of the reversible inactivation by lidocaine of the CA3 or CA1 areas of the dorsal hippocampus on acquisition, consolidation, and retrieval of a contextual fear conditioning. Whereas infusions of lidocaine never impaired elementary tone conditioning, their effects on contextual conditioning provided interesting clues about the role of these two hippocampal regions. They demonstrated first that the CA3 area is necessary for the rapid elaboration of a unified representation of the context. Secondly, they suggested that the CA1 area is rather involved in the consolidation process of contextual memory. Third, they showed that CA1 or CA3 inactivation during retention test has no effect on contextual fear retrieval when a recognition memory procedure is used. In conclusion, our findings point as evidence that CA1 and CA3 subregions of the dorsal hippocampus play important and different roles in the acquisition and consolidation of contextual fear memory, whereas they are not required for context recognition.     

d-Cycloserine: effects on long-term retention of a conditioned response and on memory for contextual attributes.

d-Cycloserine (DCS), a partial agonist of the glycine recognition site of the N-methyl d-aspartate receptor, has beneficial effects on learning and memory. In order to investigate its potential to influence learning and memory of both the response and the stimulus attributes of training, male Sprague-Dawley albino rats were trained in a one-trial inhibitory avoidance task following an acute intraperitoneal injection of DCS (3 mg/kg) or an equal volume of saline. In order to measure memory for stimulus attributes, testing involved a context shift paradigm, in which subjects are tested in either the environment of training or a different one. Good memory for the contextual attributes of training is indicated by poor performance in the alternate context. Retention was assessed either 1, 7, or 14 days after training. At 1 day, Saline subjects were affected by a change in context, while DCS subjects were not. In subjects tested 1 week following training, Saline subjects were no longer affected by a change in context, in that they performed the avoidance response in both contexts. This indicates the forgetting of stimulus attributes in Saline subjects. DCS subjects did show the context shift effect at 1 week, indicating the retention of stimulus attributes. Finally, Saline subjects demonstrated the context shift rebound at 14 days, while DCS subjects performed equivalently in both contexts. Taken together, these data suggest that DCS may enhance retention of fear and slow the forgetting of stimulus attributes.     

Analysis of treatments to alleviate forgetting in rats

Two experiments with rats investigated the effectiveness of prior-cuing treatments for alleviating forgetting of aversive conditioning. The aim was to see which retrieval cues would be most effective within different contexts. Experiment 1 examined the contexts of classical fear conditioning and instrumental avoidance training. The results indicated that the response components were sufficient to reinstate avoidance training, whereas the unconditioned stimulus (US) was most effective for classical fear conditioning. In Experiment 1, the reinforcer per se was ineffective in reinstating instrumental avoidance training. Experiment 2 manipulated the training context and found that the US could be made an effective prior-cuing treatment for instrumental training if classical conditioning components were more prevalent during training. These results are interpreted to mean that a "critical context" must be reinstated by the cuing treatment if this treatment is to promote retrieval of the memory.     

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.     

Effects on memory of early testing and accuracy assessment for central and contextual content

ABSTRACT

Memory for an event is influenced by many factors including retention interval, frequency of assessment, and type of information assessed concerning the event. We examined the usefulness of observer memory for contextual information in assessing accuracy of memory for central information. Participants viewed a video of a purse being stolen and were asked questions concerning the perpetrator and surrounding context of the event, including where and when the event occurred and who else was present. Participants tested immediately after seeing the video exhibited better memory than those tested for the first time 48 hours after the event. Additionally, testing immediately after viewing the video reduced forgetting over the 48-hour delay (i.e. early testing attenuated subsequent forgetting). Moreover, memory for the context of the event correlated positively with memory of the central information (i.e. perpetrator), and memory concerning other people at the event tended to have the highest correlation with perpetrator memory.