The standard reconsolidation protocol for auditory fear-conditioning does not account for fear to the test context.

Research on memory reconsolidation has relied heavily on the use of Pavlovian auditory cued-fear conditioning. Here, an auditory cue (CS) is paired with a footshock (US) and the CS is later able to evoke a freezing response when presented alone. Some treatments, when administered to conditioned subjects immediately following a CS-alone (memory reactivation) trial, can attenuate the freezing they display on subsequent CS-alone (test) trials, in the absence of the treatment. This reduction in conditioned freezing is usually taken as evidence that the treatment disrupts post-reactivation reconsolidation of the memory trace representing the pairing of CS and US. We suggest an alternative interpretation that may account, either in whole or in part, for the attenuated freezing. The standard reconsolidation protocol (SRP) for auditory fear-conditioning has a design feature that results in second-order conditioning of fear to the test context, as this context is paired with the fear-evoking CS on the reactivation trial. Since freezing during the CS on the test will reflect the compound influence of contextual-fear and cued-fear, a post-reactivation treatment might attenuate freezing on the test by disrupting consolidation of second-order contextual-fear conditioning, even if it has little or no effect on the stability of the original cued-fear memory. This experiment confirmed that rats tested according to the SRP, in which the reactivation and test trials occur in the same context, freeze more on the test trial than rats that receive the reactivation and test trials in different contexts. This confound could lead to false-positive evidence of disrupted reconsolidation if it is not avoided or minimized, which can be accomplished with a modified protocol.

A Go/No-go delayed nonmatching-to-sample procedure to measure object-recognition memory in rats.

The novel-object preference (NOP) test is widely used to assess object-recognition memory in rats. When interpreting behaviour on the test, a common assumption is that the magnitude of a rat's novel-object preference reflects the persistence or accuracy of its memory for the previously encountered object. However, some concerns have been raised regarding the latter interpretation, and hence, the internal validity of the NOP test as a gauge of object-recognition abilities. Given the concerns, we developed a new Go/No-go delayed nonmatching-to-sample (DNMS) procedure to measure object-recognition memory, which circumvents the interpretational problems associated with the NOP test. Rats were trained to displace an unfamiliar object (sample) from over a food well to obtain a food reward. Then on a choice phase, rats were presented with novel objects ("Go" trial) or copies of the sample object ("No-go" trial). On Go trials rats received a reward for displacing the novel object and on No-go trials no reward was provided for displacing the sample object. Rats required an average 54 sessions to reach a performance criterion of at least 80 % correct choices on five consecutive sessions (16 correct choices out of 20). Afterwards, rats were tested on the NOP test, and we found that scores on both tasks were not significantly correlated, indicating performance on the Go/No-go DNMS task did not predict novelty preference scores. The findings from this experiment reveal the benefits of an alternative approach to assess object-recognition memory in rats.

Effects of perirhinal cortex and hippocampal lesions on rats' performance on two object-recognition tasks.

The effects of hippocampal (HPC) damage on rats' novel object preference (NOP) performance have been rather consistent, in that HPC lesions do not disrupt novelty preferences on the test. Conversely, there have been inconsistent findings regarding the effects of perirhinal cortex (PRh) lesions on rats' novel-object preferences. Given the concerns that have been raised regarding the internal validity of the NOP test, viz. that the magnitude of the novel-object preference does not necessarily reflect the strength in memory for an object, it could explain the discrepant findings. The goal of the present experiment was to examine the effects of PRh and HPC lesions on rats' object-recognition memory using a new modified delayed nonmatching-to-sample (mDNMS) task, as it circumvents the interpretational problems associated with the NOP test. Rats received PRh, HPC, or Sham lesions and were trained on the mDNMS task using a short delay (∼30 s). Both PRh and HPC rats acquired the task at the same rate as Sham rats, and reached a similar level of accuracy, indicating intact object-recognition. Thereafter, rats were tested on the NOP test using a 180-s delay. Rats with HPC lesions exhibited significant novel-object preferences, however, both the PRh and Sham rats failed to show a novelty preference. The discrepancy in both the PRh and Sham rats' performance on the mDNMS task and NOP test raises concerns regarding the internal validity of the NOP test, in that the magnitude of a rat's novel-object preference does not accurately reflect the persistence or accuracy of a rat's memory for the sample object.

Assessing object-recognition memory in rats: Pitfalls of the existent tasks and the advantages of a new test.

Studies of object-recognition memory in lab rats began in the late 1980s, using variants of the trial-unique delayed nonmatching-to-sample (DNMS) task. By the end of the 20th century, most investigators who wanted to study object-recognition in rodents had abandoned the DNMS task in favor of the novel-object-preference (NOP) test, mainly because the latter test is relatively easy to employ, whereas conventional DNMS tasks are not. Some concerns have been raised, however, about the internal validity of the NOP test as a method of measuring object-recognition abilities. We describe two experiments using a new DNMS procedure which requires considerably less training than the DNMS tasks of the 1980s and 1990s, and which cannot be subject to the same criticisms that have been leveled at the NOP test. In Experiment 1, rats were trained on the new modified-DNMS (mDNMS) task using short delays. Rats successfully learned the nonmatching rule in fewer than 25 trials, and they made accurate choices with retention intervals of up to 10 min. Experiment 2 examined a different group of rats' performance on the mDNMS task following long retention intervals (72 h, 3 weeks, and ~45 weeks). Rats made accurate choices on all retention intervals, even the longest retention interval of ~45 weeks. Overall, the findings demonstrate some benefits of an alternative approach to assess object-recognition memory in rats.

Circadian time-place (or time-route) learning in rats with hippocampal lesions.

Circadian time-place learning (TPL) is the ability to remember both the place and biological time of day that a significant event occurred (e.g., food availability). This ability requires that a circadian clock provide phase information (a time tag) to cognitive systems involved in linking representations of an event with spatial reference memory. To date, it is unclear which neuronal substrates are critical in this process, but one candidate structure is the hippocampus (HPC). The HPC is essential for normal performance on tasks that require allocentric spatial memory and exhibits circadian rhythms of gene expression that are sensitive to meal timing. Using a novel TPL training procedure and enriched, multidimensional environment, we trained rats to locate a food reward that varied between two locations relative to time of day. After rats acquired the task, they received either HPC or SHAM lesions and were re-tested. Rats with HPC lesions were initially impaired on the task relative to SHAM rats, but re-attained high scores with continued testing. Probe tests revealed that the rats were not using an alternation strategy or relying on light-dark transitions to locate the food reward. We hypothesize that transient disruption and recovery reflect a switch from HPC-dependent allocentric navigation (learning places) to dorsal striatum-dependent egocentric spatial navigation (learning routes to a location). Whatever the navigation strategy, these results demonstrate that the HPC is not required for rats to find food in different locations using circadian phase as a discriminative cue.

Intra-perirhinal cortex administration of estradiol, but not an ERß agonist, modulates object-recognition memory in ovariectomized rats.

Intra-rhinal cortical infusion of 17-ß estradiol (E2, 244.8pg/µl) enhances performance on the Novel-Object Preference (NOP) test and impairs accuracy on the delayed nonmatching-to-sample (DNMS) task in the same set of ovariectomized rats (Gervais, Jacob, Brake, & Mumby, 2013). These results appear paradoxical, as normal performance on both tests require intact object-recognition memory (ORM) ability. While demonstrating a preference for the novel object requires recognizing the sample object, rodents can recognize the sample object and still fail to demonstrate a preference. Therefore, enhanced NOP test performance is consistent with both improved ORM and increased novel-object exploration independent of memory processes. There is some evidence suggesting that estrogen receptor (ER) ß agonists enhance NOP test performance (Jacome et al., 2010), but no study to date has examined the role of this receptor in DNMS task performance in rodents. The aim of the present study was to determine whether intra-PRh infusion of an ER ß agonist, diarylpropionitrile (DPN, 2µg/µl), has divergent effects on novel-object preference (i.e. novelty preference) and accuracy on the DNMS task. Ovariectomized (OVX) rats (n=7) received chronic low E2 (∼22pg/ml serum) replacement, then intra-PRh infusion of DPN (2µg/µl), E2 (244.8pg/µl), or vehicle before each mixed-delay session (0.5-5min) of the DNMS task. A different set of OVX rats (n=10) received the same infusions before each NOP test trial, and were tested either 4 or 72h later. Consistent with Gervais et al. (2013), intra-PRh E2 reduced accuracy on the DNMS task following a 5-min retention delay and enhanced novelty preference on both tests. Intra-PRh DPN was associated with accuracy that was similar to the vehicle-infusion condition, despite enhancing novelty preference on both tests. The accuracy results suggest that while intra-PRh E2 impairs ORM, ERß does not play a role. However, ERß in the PRh appears to be important for the expression of novelty preference, in a manner that is unaffected by retention delay. These findings suggest that the modulation of novelty preference by intra-PRh E2/ERß may be due to factors unrelated to ORM.

The effects of extrinsic stress on somatic markers and behavior are dependent on animal housing conditions.

Properties of the environment play an important role in animal wellbeing and may modulate the effects of external threats. Whereas stressors can affect emotion and impair cognition, environmental enrichment may prevent the occurrence of such negative sequelae. Animals exposed to semi-natural group-housing experience a complex environment; whereas environmental enrichment might protect against stressors, a socially-enriched environment(SEE) could entail aggressive inter-male encounters with additive stress effects. In the present study, we investigated the effects of exposure to external stressors, footshocks and forced swimming, on adrenal gland and body weights as well as on behavior in rats housed under SEE or standard, non-enriched environment (NEE), conditions. We found that SEEs reduced the anxiogenic effects of stress. Moreover, SEEs improved the performance in an operant task and prevented the increase in impulsive behavior produced by external stressors on NEE animals. Whereas these findings are indicative of stress-buffering effects of SEEs, adrenal gland weights were increased while total body weights were decreased in SEE rats, suggesting that SEEs may simultaneously exacerbate physiological measurements of stress. Finally, in the SEE, total aggressive behaviors and body wounds were paradoxically reduced in animals that received external stressors in comparison to non-stressed controls. The consequences of the external stressors applied here are not uniform, varying according to the housing condition and the outcome considered.

Attenuation of dendritic spine density in the perirhinal cortex following 17ß-Estradiol replacement in the rat.

Intraperirhinal cortex infusion of 17-ß estradiol (E2) impairs object-recognition memory. However, it is not currently known whether this hormone modulates synaptic plasticity in this structure. Most excitatory synapses in the central nervous system are located on dendritic spines, and elevated E2 levels influence the density of these spines in several brain areas. The goal of the present study was to determine whether differences in dendritic spine density in the perirhinal cortex are observed following high E2 replacement in ovariectomized rats. The density of total spines, and mushroom-shaped (i.e. mature) spines were compared between a high E2 replacement (10 µg/kg/day, s.c.) and a no replacement condition. The perirhinal cortex is subdivided into Broadmann's area 35 and 36 and so group comparisons were made within each sub-region separately. High E2 replacement resulted in lower density of mushroom-shaped spines in area 35 relative to no replacement. There was no effect of high E2 replacement on dendritic spine density in area 36. These findings are consistent with the idea that higher E2 levels reduce dendritic spine density in area 35, which may result from spine shrinkage, or reduced synapse formation. This study provides preliminary evidence for a mechanism through which E2 may impair object-recognition memory.

Oxytocin and object preferences in the male prairie vole.

The neuropeptide oxytocin has been previously associated with social attachment behaviors in various species. Studies in socially monogamous prairie voles (Microtus ochrogaster) and other species have implicated oxytocin in partner preferences and other social behaviors. In the present study male prairie voles were injected intraperitoneally with either oxytocin or the selective oxytocin antagonist, L-368,899, and were assessed for object preference (for small inanimate toys) 30-min after injection. Object preferences were assessed in animals tested alone or in the presence of their sibling cage mate. Saline-treated controls displayed preferences for the novel object, both when tested alone and in pairs, while oxytocin-treated voles did not demonstrate an object preference, regardless of whether tested alone or in pairs. Finally, oxytocin antagonist treated voles showed preference for the novel object, but only when tested in pairs. These data support a possible involvement of oxytocin and oxytocin receptors in object preference.

Retrograde and anterograde memory following selective damage to the dorsolateral entorhinal cortex.

Anatomical and electrophysiological evidence suggest the dorsolateral entorhinal cortex (DLEC) is involved in processing spatial information, but there is currently no consensus on whether its functions are necessary for normal spatial learning and memory. The present study examined the effects of excitotoxic lesions of the DLEC on retrograde and anterograde memory on two tests of allocentric spatial learning: a hidden fixed-platform watermaze task, and a novelty-preference-based dry-maze test. Deficits were observed on both tests when training occurred prior to but not following n-methyl d-aspartate (NMDA) lesions of DLEC, suggesting retrograde memory impairment in the absence of anterograde impairments for the same information. The retrograde memory impairments were temporally-graded; rats that received DLEC lesions 1-3 days following training displayed deficits, while those that received lesions 7-10 days following training performed like a control group that received sham surgery. The deficits were not attenuated by co-infusion of tetrodotoxin, suggesting they are not due to disruption of neural processing in structures efferent to the DLEC, such as the hippocampus. The present findings provide evidence that the DLEC is involved in the consolidation of allocentric spatial information.

Centrally-administered oxytocin promotes preference for familiar objects at a short delay in ovariectomized female rats.

Oxytocin has been previously associated with social attachment behaviors in various species, however, most studies focused on partner preference in the socially-monogamous prairie vole. In these, oxytocin treatment was shown to promote partner preference, such that females receiving either central or pulsatile peripheral administration would spend more time with a familiar male. This behavioral outcome was blocked by oxytocin receptor antagonist treatment. The aim of the current study was to further explore the preference-inducing properties of oxytocin by examining its effects on object preference on ovariectomized female rats. In other words, we assessed whether these effects would apply to objects and if they would be persistent across species. Eight rats were infused with oxytocin into the left ventricle and object preference was assessed at two delays: 30min and 4h. At the 30min delay, oxytocin-treated animals showed preference for the familiar object, whereas saline-treated controls exhibited preference for the novel object. At the 4h delay, both groups showed novel-object preference. Our findings show that oxytocin modulates object preference in the female rat at a shorter delay, similar to the findings from partner-preference studies in the prairie vole, suggesting that the mechanisms driving object preference might be in part similar to those responsible for partner preference.

Modulatory effect of 17-ß estradiol on performance of ovariectomized rats on the Shock-Probe test.

17-ß estradiol (E2) has been shown to modulate fear conditioning by influencing freezing behavior following re-exposure to either the conditioning context or a cue associated with shock. Fear-related behaviors other than freezing may be influenced differently by E2 replacement. Accordingly, the present study examined whether E2 modulates fear conditioning using the Shock-Probe test, which allows for the observation of multiple fear responses. Ovariectomized (OVX) rats were divided into three groups: no E2 replacement (Shock-Oil; 0.1ml/kg sesame oil), high E2 replacement (Shock-E2; 3 daily doses of 10µg/kg, s.c.), and a no shock, no E2 replacement (Naïve-oil) group. During the acquisition phase, the two shock groups (Shock-Oil and Shock-E2) demonstrated comparable fear expression on all measures. During the retention tests, rats without E2 replacement demonstrated intact contextual-fear conditioning but impaired cued-fear conditioning, while rats with E2 replacement demonstrated the opposite pattern. In the context paired with shock, the Shock-Oil group spent more time burying the probe than both the Naïve-oil group and Shock-E2 group. The Shock-E2 group avoided the probe area relative to the other two groups when tested in the context unpaired with shock. The present findings demonstrate the importance of using multiple behaviors to measure fear conditioning and suggest that high E2 replacement impairs contextual and facilitates cued fear conditioning.

Systemic and intra-rhinal-cortical 17-ß estradiol administration modulate object-recognition memory in ovariectomized female rats.

Previous studies using the novel-object-preference (NOP) test suggest that estrogen (E) replacement in ovariectomized rodents can lead to enhanced novelty preference. The present study aimed to determine: 1) whether the effect of E on NOP performance is the result of enhanced preference for novelty, per se, or facilitated object-recognition memory, and 2) whether E affects NOP performance through actions it has within the perirhinal cortex/entorhinal cortex region (PRh/EC). Ovariectomized rats received either systemic chronic low 17-ß estradiol (E2; ~20 pg/ml serum) replacement alone or in combination with systemic acute high administration of estradiol benzoate (EB; 10 µg), or in combination with intracranial infusions of E2 (244.8 pg/µl) or vehicle into the PRh/EC. For one of the intracranial experiments, E2 was infused either immediately before, immediately after, or 2 h following the familiarization (i.e., learning) phase of the NOP test. In light of recent evidence that raises questions about the internal validity of the NOP test as a method of indexing object-recognition memory, we also tested rats on a delayed nonmatch-to-sample (DNMS) task of object recognition following systemic and intra-PRh/EC infusions of E2. Both systemic acute and intra-PRh/EC infusions of E enhanced novelty preference, but only when administered either before or immediately following familiarization. In contrast, high E (both systemic acute and intra-PRh/EC) impaired performance on the DNMS task. The findings suggest that while E2 in the PRh/EC can enhance novelty preference, this effect is probably not due to an improvement in object-recognition abilities.

Enhanced adolescent learning and hippocampal axonal projections following preadolescent spatial exposure to a water or dry maze.

The present work sought to determine whether preadolescent exposure to a different task in the same spatial environment would lead to enhancement of water-maze performance and changes in hippocampal connectivity. Separate groups of preadolescent (p16-p26) Long Evans rats (LER) were exposed to the same room and arena using either a water-maze (WM) or a dry-maze (DM), while a third group received no exposure to the spatial cues (NT) but were handled. Three weeks later, rats were tested on the WM or DM task in the same room where preadolescent exposure took place. This set up conditions where the DM/WM and WM/DM groups were exposed to the same spatial cues during the preadolescent and adolescent (p40-p44) phases but performed different tests allowing for the dissociation of spatial cue exposure and task familiarity on adolescent performance. When animals experienced similar preadolescent and adolescent conditions (WM/WM or DM/DM), there was improved performance over animals with no preadolescent spatial exposure (NT/WM or NT/DM). In group DM/WM, there was enhanced adolescent performance compared to group NT/WM. In contrast, group WM/DM did not show enhanced adolescent performance. Compared to groups with no preadolescent spatial exposure, groups with both preadolescent and adolescent spatial exposure showed elevated synaptophysin staining in the hippocampal CA3 region indicating an expanded axonal projection in this region. These data suggest the possibility that exposure to spatial cues during the preadolescent period, independent from task-specific requirements, contributes to enhanced adolescent spatial performance on the WM. This appears to be linked with the reorganization of axonal inputs to the CA3 region.

Prolonged inactivation of the hippocampus reveals temporally graded retrograde amnesia for unreinforced spatial learning in rats.

We investigated whether systems consolidation of spatial memory could be detected in a non-navigational, spatial-learning test that takes advantage of rats' natural propensity to preferentially investigate an object that was displaced relative to spatial cues more than an object that remained stationary. Previous studies using navigational spatial-learning tests have generally failed to reveal temporally-graded retrograde amnesia, possibly because the hippocampus needs to be intact for the retrieval and/or processing of navigational information during the test. In the present study, the hippocampus of rats was kept inactivated, at two sites along its septo-temporal axis (dorsal and intermediate), for four consecutive days, beginning either 3h or 5 days after familiarization to two identical objects in an open field. Rats that had their hippocampus inactivated beginning 5 days but not 3h after familiarization showed evidence that they remembered the previous location of the displaced object. The results suggest that systems consolidation of spatial memories can be detected using a non-navigational test of spatial memory.

Object familiarization and novel-object preference in rats.

We investigated whether object familiarization was related to novel-object preference in the novel-object preference (NOP) test in rats. In Experiment 1, we found that no significant correlation existed between the time spent investigating 2 identical copies of a sample object and the degree of preference for a novel object. In Experiment 2, rats investigated 2 identical sample objects for a total of 5, 30, 60, 90 or 120s. Investigatory preference for the novel object was compared to chance expectancy as well as between the groups. Only the 90-s group and the 120-s group displayed above-chance investigatory preference for the novel object, but novel-object preference for these 2 groups did not differ from each other, suggesting that a minimal amount of sample object investigation is necessary for rats to develop a novel-object preference, beyond which no increase in novel-object preference was found. In Experiments 3 and 4, normal rats and rats with hippocampal lesions were given repeated test trials, with the same sample object presented with a different novel object, at 24-h and (Experiment 3) and 35-s intervals (Experiment 4). In both experiments, novel-object preference did not increase in magnitude with repeated sample object exposures, suggesting that increased familiarity with the sample object does not result in increased novel-object preference. Rats with lesions of the dorsal hippocampus showed an unreliable investigatory preference for the novel object. These results are discussed in terms of the potential limitations of the NOP test as a tool for the assessment of object-recognition memory in rats.

Incidental (unreinforced) and reinforced spatial learning in rats with ventral and dorsal lesions of the hippocampus.

We investigated whether the ventral and dorsal hippocampus were differentially involved in incidental spatial learning. Rats with ventral and dorsal hippocampal lesions were tested on an unreinforced test of spatial memory that takes advantage of their natural propensity to explore novelty. Rats were presented with two copies of an identical object in a large circular open field arena. Subsequently, the rats were placed back into the open field with one of the objects displaced to an adjacent quadrant of the arena. Sham-operated rats and rats with ventral hippocampal lesions spent more time in the quadrant that contained the displaced object than in the quadrant that contained the non-displaced object, and more time investigating the displaced object than the non-displaced object. Rats with dorsal hippocampal lesions were impaired on both measures. Both sham and ventral hippocampal lesioned rats subsequently learned to retrieve a food pellet in the ends of each arm of a radial maze. Rats with lesions to the dorsal hippocampus showed no significant improvement in the number of errors made across training sessions and made significantly more errors, overall, than rats with ventral hippocampal or sham lesions. The findings suggest that an intact dorsal but not ventral hippocampus is necessary for spatial learning in rats.

Patterns of retrograde amnesia for recent and remote incidental spatial learning in rats.

A non-navigational test of incidental spatial learning was used to determine whether hippocampal damage causes temporally-graded retrograde amnesia (TGRA) for allocentric-spatial information. Rats were exposed to two identical objects in a circular open field for 7 min on seven consecutive days. In the 1-3 days after the last day of familiarization, rats received neurotoxic lesions of the hippocampal formation (HPC) or sham lesions. Another two groups received the same lesions 3 weeks after familiarization. The rats were then placed back in the open field with one object displaced, and the time spent in each of the quadrants as well as time spent exploring the objects was recorded. Rats that received HPC lesions 3 weeks but not 1-3 days after familiarization showed evidence of preserved remote spatial memory; however, their remote memory was expressed through different behavior than control rats. Rats with HPC lesions spent more time with the displaced object than with the object that remained in the same place, whereas control rats spent more time in the quadrant where the displaced object used to be. These results suggest that remote spatial memories may be preserved with a sufficiently long familiarization-to-surgery interval before HPC lesions, but that the nature of these memories may differ in quantity and/or quality from those of intact rats.

A limited role for the hippocampus in the modulation of novel-object preference by contextual cues.

Recent evidence suggests that rats require an intact hippocampus in order to recognize familiar objects when they encounter them again in a different context. The two experiments reported here further examined how changes in context affect rats' performance on the novel-object preference (NOP) test of object-recognition memory, and how those effects interact with the effects of HPC damage. Rats with HPC lesions and control rats received NOP testing in either the same context in which they had previously encountered sample objects, or in a different but equally familiar context. In Experiment 1, the two contexts had very few overlapping cues within or outside the apparatus; thus, the differences between them were global. Consistent with previous results, control rats showed a novel-object preference in both the unchanged and (globally) changed contexts, whereas rats with HPC lesions displayed a preference only in the unchanged context. In Experiment 2, the context shift included only local features proximal to the test objects. The main results were the reverse of Experiment 1--rats with HPC lesions displayed a novel-object preference in both the unchanged and (locally) changed contexts, whereas control rats displayed a preference only in the unchanged context. The findings are consistent with the view that HPC damage does not cause a general inability to recognize objects, nor an inability to encode or store a representation of the context in which the objects are encountered. They suggest instead that HPC damage impairs the ability to remember specific locations of familiar objects within a particular context.

Perirhinal cortex damage and anterograde object-recognition in rats after long retention intervals.

Damage to the perirhinal cortex (PRh) in rats impairs anterograde object-recognition memory after retention intervals of up to several hours, but there is little direct evidence to link PRh function to object-recognition abilities after substantially longer intervals that span several days or weeks. We assessed the effects of PRh lesions on anterograde object recognition using a novel-object preference test, with retention intervals lasting 24 h and 3 weeks. The rats received multiple exposures to the sample object during the learning phase--5 min per day on 5 consecutive days. Control rats displayed a significant novel-object preference after both retention intervals, indicating recognition of the sample object, whereas the rats with PRh lesions displayed a significant preference after the 24-h interval, but not after the 3-week interval. When the learning phase of the trial was shortened to a single 5-min session, the PRh group was impaired in the 24-h condition. The findings indicate that the disruptive effects of PRh damage on anterograde object recognition persist over very long postlearning intervals. The results indicate further that object recognition impairments following PRh damage are not ubiquitous, and that learning conditions play a significant role in determining the subsequent recognition performance in rats with PRh damage.