Post-training reversible inactivation of hippocampus reveals interference between memory systems

A post-training reversible lesion technique was used to examine the effects of neural inactivation of the dorsal hippocampus on place and response learning. Male Long-Evans rats trained in one of two versions of a water plus-maze task received post-training intra-hippocampal infusions of the local anesthetic drug bupivacaine (0.75% solution, 0.5 microl), or saline. Post-training intra-hippocampal infusions of bupivacaine attenuated acquisition of the place task and enhanced acquisition of the response task. Delayed (2-h) post-training infusions of bupivacaine did not affect retention in either task. The findings demonstrate (1) enhanced learning after reversible hippocampal lesions that is independent of treatment influences on non-mnemonic factors, and (2) inactivation of the dorsal hippocampus during the post-training memory consolidation period is sufficient to enhance response learning.     

The molecular cascades of long-term potentiation underlie memory consolidation of one-trial avoidance in the CA1 region of the dorsal hippocampus, but not in the basolateral amygdala or the neocortex

Data accumulated through the past 15 years showed that memory consolidation of one-trial avoidance learning relies on a sequence of molecular events in the CA1 region of the hippocampus that is practically identical to that of long-term potentiation (LTP) in that area. Recent findings have indeed described CA1 LTP concomitant to the consolidation of this and other tasks. However, abundant evidence suggests that, in addition, other molecular events, involving some of the same steps but with different timing and in different sequence in the basolateral amygdala, entorhinal, parietal and cingulate cortex are as important as those of the hippocampus for memory consolidation. Here we review the hippocampal mechanisms involved and the possible interconnections between all these processes. Overall, the findings indicate that memory consolidation of even a task as deceivingly simple as one-trial avoidance relies on hippocampal LTP but also requires the concomitant participation of other brain systems and molecular events. Further, they point to the mechanisms that account for the enhanced consolidation usually seen for emotionladen memories.     

Hippocampus and remote spatial memory in rats

Damage to the hippocampus typically produces temporally graded retrograde amnesia, whereby memories acquired recently are impaired more than memories acquired remotely. This phenomenon has been demonstrated repeatedly in a variety of species and tasks. It has also figured prominently in theoretical treatments of memory and hippocampal function. Yet temporally graded retrograde amnesia has not been demonstrated following hippocampal damage in spatial tasks like the water maze. We have assessed recent and remote spatial memory following hippocampal lesions in three different tests of spatial memory: (1) the standard water maze; (2) the Oasis maze, a dry-land version of the water maze; and (3) the annular water maze, where training and testing occur within a circular corridor. Training protocols were developed for each task such that retention of spatial memory could be expressed after very long retention intervals. In addition, retention in each task was assessed with single probe trials so that the assessment of remote memory did not depend on the ability to relearn across multiple trials. The findings were consistent across the three tasks. In the standard water maze (Experiment 1), spatial memory was impaired after training-surgery intervals of 1 day, 8 weeks, or 14 weeks. Similarly, in the Oasis maze (Experiment 2), spatial memory was impaired after training-surgery intervals of 1 day and 9 weeks. Finally, in the annular water maze (Experiment 3), spatial memory was impaired after training-surgery intervals of 9 weeks and 14 weeks. Dorsal hippocampal lesions impaired performance to the same extent as complete lesions. The impairment in remote spatial memory could reflect disruption of previously acquired spatial information. Alternatively, it is possible that in these tasks hippocampal lesions might produce an impairment in performance that prevents the expression of an otherwise intact spatial memory.     

Inhibitory avoidance learning alters the amygdala calcium/calmodulin-dependent protein kinase II activity in rats

This study investigated the role of amygdala CaM-kinase II (calcium/calmodulin-dependent protein kinase II) in affective learning and memory. In Experiment I, two groups of rats were trained on a one-trial step through inhibitory avoidance learning task. The experimental group received a high intensity foot shock contingent upon the stepping-through behavior, whereas the control group received a series of non-contingent low intensity foot shock during training. The experimental rats showed significantly higher retention scores than the control rats. Correspondingly, rats in the experimental group showed significantly higher Ca²⁺-independent activity of CaM-kinase II than the controls. Intra-amygdala injection of a specific CaM-kinase II inhibitor, KN-62, before the training trial disrupted affective learning. In comparison with the vehicle-injected controls, pretraining injection of KN-62 impaired the acquisition of affective specific learning. These results, taken together, indicated that the activation of amygdala CaM-kinase II in the amygdala is associated with the affective learning behavior, and may be one of the neural mechanisms underlying formation of affective memory.     

Lesions of the stria terminalis attenuate the enhancing effect of post-training epinephrine on retention of an inhibitory avoidance response

This study investigated the effect of the stria terminalis (ST) lesions on the retention facilitation produced by post-training epinephrine. Rats with sham or bilateral ST lesions were trained on a one-trial step-through inhibitory avoidance task and, immediately after training, received saline or one of 3 doses (0.01, 0.1 or 1.0 mg/kg, s.c.) of epinephrine. In the rats with sham ST lesions, all 3 doses of epinephrine significantly enhanced retention performance. Lesions of the ST did not affect retention significantly. However, the lesions attenuated the facilitating effect of epinephrine on retention. These findings suggest that the integrity of the ST, which connects the amygdala and other brain structures, is essential for the effect of epinephrine on memory processes. The possible involvement of the brain structures processing visceral information in the memory modulatory effect of epinephrine is discussed.     

Involvement of a basolateral amygdala complex-nucleus accumbens pathway in glucocorticoid-induced modulation of memory consolidation

Systemic or intracerebral administration of glucocorticoids modulates memory consolidation in several tasks. Previously, we have shown that these memory-modulatory effects depend on an intact basolateral complex of the amygdala (BLC) and efferents from the BLC that run through the stria terminalis. It is currently unknown, however, what BLC efferent structures mediate these effects. The present experiments were designed to determine whether the nucleus accumbens (NA), which receives BLC efferents through the stria terminalis and is involved in several BLC-dependent behaviours, is involved in glucocorticoid-induced modulation of memory consolidation. In experiment 1, rats with bilateral sham or N-methyl-D-aspartate (NMDA)-induced lesions of the NA were trained on a one-trial, footshock-motivated inhibitory avoidance task, and given immediate post-training injections of either the synthetic glucocorticoid dexamethasone (0.3 or 1.0 mg/kg, s.c.) or vehicle. Testing 48 h later revealed that dexamethasone significantly enhanced retention in sham-lesioned rats but that the enhancing effect was blocked in NA-lesioned rats. An asymmetrical, or crossed-lesion design was employed in experiment 2. Rats with a unilateral NMDA-induced lesion of the BLC and a unilateral lesion of either the ipsilateral or contralateral NA were trained as in experiment 1. Testing 48 h later revealed that dexamethasone enhanced retention in ipsilaterally lesioned rats, but that this effect was blocked in contralaterally lesioned rats. These findings indicate that an intact BLC-NA pathway is critical for the enhancing effects of glucocorticoids on memory consolidation, and are consistent with the view that the BLC regulates memory consolidation in other brain regions.     

Intact Behavioral Expression of Contextual Fear,Context Discrimination,and Object Discrimination Memories Acquired in the Absence of the Hippocampus

We test the hypothesis that the stability and precision of context and visual discrimination memories depend on interactions between the hippocampus (HPC) and other memory storage networks. In four experiments we tested the properties of memories acquired in the absence of the HPC. Long–Evans male rats were exclusively used in all experiments. Experiment 1 evaluated acquisition and retention of context fear memories in rats with prior partial or complete HPC damage. Confirming an earlier report (Zelikowsky et al., 2012) a very small but statistically reliable slowing in a single session of context fear conditioning was found after HPC damage. In contrast, retention of context fear memory was normal after HPC damage up to 30 d after learning. In experiment 2, we found that discrimination between a context paired with foot shocks and a different context never paired with foot shock was retained normally for 15 d. In experiment 3, we replicated the finding of intact context discrimination for at least 15 d in rats who display a significant impairment in acquisition of place learning in the Morris water task (MWT). In final experiment using an appetitive object discrimination task, we showed normal retention of the discrimination for at least 30 d after training in rats with complete HPC damage. These finding score against the idea that non HPC memory storage requires a period of interaction with HPC to establish a stable, precise memory.SIGNIFICANCE STATEMENT Contrary to expectations from systems memory consolidation, we find that in the absence of a functional hippocampus (HPC) context and visual memories are formed rapidly and exhibit normal persistence and precision. The findings suggest that the HPC is not obligatory for these features of long-term memories.     

Lidocaine reversible inactivation of the median raphe nucleus has no effect on reference memory but enhances working memory versions of the Morris water maze task

Numerous studies in the past have dealt with the role of serotonergic system lesions in tasks aimed at measurement of cognitive behavior, but the literature concerning the role of serotonin in cognition remains controversial. Rats with electrolytic lesions of the median raphe nucleus (MRN) were found to display a profound impairment in both the acquisition and retention of spatial memory task. In this study, the lidocaine inactivation was employed to evaluate the involvement of the rat's median raphe nucleus in reference and working memory versions of the Morris water maze (MWM) task. Lidocaine (0.5 microl, 2%) was injected through a single cannula aimed at the MRN; control groups were treated in the same way with a 0.5 microl injection of saline. In Experiment 1, rats were trained in a reference memory version of the MWM with two blocks of four trials per day for three consecutive days, with intra-cerebral injection made 5 min before training. No significant difference was found. In Experiment 2, intra-cerebral injection was applied immediately after two blocks of four trials, and in Experiment 3, the drug was injected 5 min before retention test in rats that had received eight trials per day on three consecutive days. Again, no significant difference between control and treatment groups was found. These results indicate that MRN has no role in acquisition, consolidation and retrieval of spatial reference memory. In subsequent experiments, rats were trained in a working memory version of the MWM task to find a new target position in trial 1, and retrieval was tested 75 min later. MRN inactivation 5 min before (Experiment 4) and immediately after the acquisition trial (Experiment 5) enhanced spatial working memory. It is concluded that normal activity of the MRN has no role in formation and retrieval of reference memory, but it has an inhibitory role in working memory. Our results are confirmed with other studies suggesting that the serotonergic system has a different role in long-term and short-term memory. Interaction with other neurotransmitter systems like acetylcholine may be involved in this case.     

Post-training amygdaloid lesions impair retention of an inhibitory avoidance response

The study examined the effect of pre- and post-training bilateral amygdaloid lesions on retention of a one-trial inhibitory avoidance response. Groups of rats, including unimplanted controls and implanted controls, were trained and tested for retention at 4, 7 or 12 days following training. The lesions were made at one of several intervals before or after training: 2 days before, immediately after, or 2, 5 or 10 days after. At all retention intervals the retention of implanted controls was poorer than that of unimplanted controls and, in comparison with both control groups, the retention of animals lesioned before training was impaired. Retention was also impaired by the post-training lesions. The degree of impairment varied with the interval between the training and the lesion: lesions made within 2 days following training impaired retention, while lesions made 10 days following training had no impairing effect. These findings suggest that posttraining lesions of the amygdala affect retention by impairing time-dependent processes involved in memory storage. With a sufficiently long training-lesion interval (10 days) an intact amygdala is not essential for retention.     

Lesions of the stria terminalis attenuate the amnestic effect of amygdaloid stimulation on avoidance responses

The present study investigated the involvement of two amygdala pathways, the stria terminalis (ST) and the ventral amygdalofugal pathway (VAF), in the effect of post-training electrical stimulation of the amygdala on retention. Rats with implanted amygdaloid electrodes and ST lesions, VAF transections or sham pathway operations, were trained on an inhibitory avoidance task and an active avoidance task. Electrical stimulation of the amygdala was given immediately after training and retention was tested 24 h later. In rats with sham ST lesions, post-training amygdaloid stimulation impaired retention in both tasks. Lesions of the ST did not significantly affect retention in the unstimulated rats. However, the ST lesions attenuated the amnestic effect of amygdaloid stimulation. In rats with sham VAF transections, stimulation of the amygdala impaired retention in the inhibitory avoidance task but enhanced retention in the active avoidance task. Transecting the VAF impaired retention performance of the unstimulated rats in the inhibitory avoidance task. However, the VAF transections did not alter the effect of amygdaloid stimulation: in both tasks, the retention performance of stimulated rats with VAF transections did not differ from that of stimulated rats with sham transections. These findings suggest that the ST may be involved in mediating the influences of the stimulated amygdala in modulating memory storage processing in the brain.     

Dissociated theta phase synchronization in amygdalo- hippocampal circuits during various stages of fear memory

The amygdala and the hippocampus are critically involved in the formation and retention of fear memories. However, their precise contribution to, and their interplay during, fear memory formation are not fully understood. In the present study we investigated network activities in the amygdalo-hippocampal system of freely behaving mice at different stages of fear memory consolidation and retention. Our data show enhanced theta phase synchronization in this pathway during the retrieval of fear memory at long-term (24 h post-training), but not short-term (2 min, 30 min and 2 h post-training) stages, following both contextual and auditory cued conditioning. However, retrieval of remotely conditioned fear (30 days post-training) failed to induce an increase in synchronization despite there still being memory retention. Thus, our data indicate that the amygdalo-hippocampal interaction reflects a dynamic interaction of ensemble activities related to various stages of fear memory consolidation and/or retention, and support the notion that recent and remote memories are organized through different network principles.     

The effects of NMDA-induced retrohippocampal lesions on performance of four spatial memory tasks known to be sensitive to hippocampal damage in the rat

Four separate cohorts of rats were employed to examine the effects of cytotoxic retrohippocampal lesions in four spatial memory tasks which are known to be sensitive to direct hippocampal damage and/or fornix-fimbria lesions in the rat. Selective retrohippocampal lesions were made by means of multiple intracerebral infusions of NMDA centred on the entorhinal cortex bilaterally. Cell damage typically extended from the lateral entorhinal area to the distal ventral subiculum. Experiment 1 demonstrated that retrohippocampal lesions spared the acquisition of a reference memory task in the Morris water maze, in which the animals learned to escape from the water by swimming to a submerged platform in a fixed location. In the subsequent transfer test, when the escape platform was removed, rats with retrohippocampal lesions tended to spend less time searching in the appropriate quadrant compared to controls. Experiment 2 demonstrated that the lesions also spared the acquisition of a working memory version of the water maze task in which the location of the escape platform was varied between days. In experiment 3, both reference and working memory were assessed using an eight-arm radial maze in which the same four arms were constantly baited between trials. In the initial acquisition, reference memory but not working memory was affected by the lesions. During subsequent reversal learning in which previously baited arms were now no longer baited and vice versa, lesioned animals made significantly more reference memory errors as well as working memory errors. In experiment 4, spatial working memory was assessed in a delayed matching-to-position task conducted in a two-lever operant chamber. There was no evidence for any impairment in rats with retrohippocampal lesions in this task. The present study demonstrated that unlike direct hippocampal damage, retrohippocampal cell loss did not lead to a general impairment in spatial learning, implying that the integrity of the retrohippocampus and/or its interconnection with the hippocampal formation is not critical for normal hippocampal-dependent spatial learning and memory. This outcome is surprising for a number of current hippocampal theories, and suggests that other cortical as well as subcortical inputs to the hippocampus might be of more importance, and further raises the question regarding the functional significance of the retrohippocampal region. Introduction     

Retrograde amnesia and selective damage to the hippocampal formation: memory for places and object discriminations

Using a within-subjects design, rats were trained on two place-memory problems and five object-discrimination problems at different intervals prior to receiving either ibotenate lesions of the hippocampal formation or sham surgery. Places # 1 and 2 were fixed-platform water-maze tasks that were run in different rooms and they were learned during the 14th and 2nd week before surgery, respectively. Object-discrimination problems # 1-5 were learned during the 13th, 10th, 7th, 4th, and 1st week before surgery, respectively. Rats with hippocampal lesions displayed impaired retention of both Place problems with no evidence of a temporal gradient to the impairment. In contrast to their retrograde place-memory deficits, the hippocampal rats displayed normal retention of the five object-discriminations that were learned before surgery. Hippocampal lesions had similar consequences for anterograde learning, as the lesioned rats were impaired in acquisition of a new water-maze problem that was run in a third room (Place #3), whereas they showed normal acquisition of two new object-discriminations. The findings indicate that the hippocampal formation is not required for long-term consolidation of information underlying accurate performance of object-discriminations, and that its critical role in memory for places persists for at least 14 weeks, and probably for as long as those memories exist.     

Impaired remote spatial memory after hippocampal lesions despite extensive training beginning early in life

Damage to the hippocampus typically produces temporally graded retrograde amnesia, whereby memories acquired recently are impaired more than memories acquired remotely. This phenomenon has been demonstrated repeatedly in a variety of species and tasks, and it has figured prominently in theoretical treatments of memory and hippocampal function. A striking exception to the finding of temporally graded retrograde amnesia comes from studies with rodents using spatial tasks like the water maze. In these studies, recent and remote memory were similarly impaired following hippocampal lesions. In contrast to work with rodents, studies of patients with medial temporal lobe lesions, including complete hippocampal lesions, indicate that remote spatial memory can be intact. One difference between studies in humans and studies in rodents is that spatial memory in animal studies is acquired during a limited period of time when the animals are adults. In contrast, the spatial memory studied in humans was acquired beginning at an early age and learning continued for a considerable period of time. We initiated training in a standard water maze immediately after rats had been weaned at 21 days of age and continued training until the rats were young adults (90 days old). Large hippocampal lesions were made 100 days after the completion of training. After recovery from surgery, control rats exhibited good retention on the first retention probe trial, but rats with hippocampal lesions performed at chance. Thus, even after extended training beginning early in life, and with a prolonged training-surgery interval, hippocampal lesions impair performance in the water maze task. Possible reasons for these findings are discussed in the context of the specific performance requirements of the water maze task.     

Basolateral Amygdala Lesions Block the Memory-enhancing Effect of Glucocorticoid Administration in the Dorsal Hippocampus of Rats

These experiments examined the effects of bilateral amygdala nuclei lesions on modulation of memory storage induced by bilateral intrahippocampal microinfusions of glucocorticoids in male Sprague-Dawley rats. Post-training infusions of the glucocorticoid receptor (type II) agonist RU 28362 (3.0 or 10.0 ng) enhanced inhibitory avoidance retention, and infusions of the glucocorticoid receptor antagonist RU 38486 (3.0 or 10.0 ng) administered shortly before training in a water maze spatial task did not affect acquisition, but impaired retention. In both tasks, neurochemically induced lesions of the basolateral but not of the central amygdala blocked the memory-modulatory effects of the intrahippocampal infusions of the drugs affecting glucocorticoid receptors. Lesions of the central amygdala alone impaired inhibitory avoidance retention, but basolateral amygdala lesions alone did not affect acquisition or retention in either task. These findings are consistent with previous evidence indicating that lesions of the basolateral amygdala block the memory-modulatory effects of systemically administered glucocorticoids, and provide further evidence that the basolateral amygdala is a critical area involved in regulating glucocorticoid effects in other brain regions involved in memory storage.     

Disruption of ripple‐associated hippocampal activity during rest impairs spatial learning in the rat

The hippocampus plays a key role in the acquisition of new memories for places and events. Evidence suggests that the consolidation of these memories is enhanced during sleep. At the neuronal level, reactivation of awake experience in the hippocampus during sharp‐wave ripple events, characteristic of slow‐wave sleep, has been proposed as a neural mechanism for sleep‐dependent memory consolidation. However, a causal relation between sleep reactivation and memory consolidation has not been established. Here we show that disrupting neuronal activity during ripple events impairs spatial learning. We trained rats daily in two identical spatial navigation tasks followed each by a 1‐hour rest period. After one of the tasks, stimulation of hippocampal afferents selectively disrupted neuronal activity associated with ripple events without changing the sleep‐wake structure. Rats learned the control task significantly faster than the task followed by rest stimulation, indicating that interfering with hippocampal processing during sleep led to decreased learning. © 2009 Wiley‐Liss, Inc.     

Experience-dependent Facilitating Effect of Corticosterone on Spatial Memory Formation in the Water Maze

Stress-related adrenal steroid hormones modulate brain and cognitive function. Electrophysiological studies, including primed burst potentiation and long-term potentiation, have indicated concentration-dependent inverted U-shape effects of corticosterone in hippocampal function and plasticity. Here, we explored the role of corticosterone in the consolidation and long-term retrieval of spatial learning in the Morris water maze task in rats. We postulated that corticosterone actions might be experience-dependent with regard to stimulus intensity, such as differential water temperatures. Indeed, rats trained at 19°C showed a quicker rate of acquisition and better long-term retention than rats trained at 25°C water. In addition, post-training corticosterone levels, on the first training day, were significantly higher in rats in the 19°C group than in the 25°C group. Performance of rats trained at 25°C, but not at 19°C, water was improved by injecting them i.p. with corticosterone immediately after each training session. Thus, the effect of exogenously administered corticosterone appears to be experience-dependent, with the experience-induced corticosterone concentrations as a critical factor determining the cognitive consequences of steroid treatment. Therefore, this work indicates a facilitating corticosterone action, during the post-training period, on the neural mechanisms determining the strength of information storage under acute, physiological conditions.     

The hippocampus is necessary for the consolidation of a task that does not require the hippocampus for initial learning

During sleep, the hippocampus plays an active role in consolidating memories that depend on it for initial encoding. There are hints in the literature that the hippocampus may have a broader influence, contributing to the consolidation of memories that may not initially require the area. We tested this possibility by evaluating learning and consolidation of the motor sequence task (MST) in hippocampal amnesics and demographically matched control participants. While the groups showed similar initial learning, only controls exhibited evidence of overnight consolidation. These results demonstrate that the hippocampus can be required for normal consolidation of a task without being required for its acquisition, suggesting that the area plays a broader role in coordinating memory consolidation than has previously been assumed.     

Intra hippocampal injection of testosterone impaired acquisition, consolidation and retrieval of inhibitory avoidance learning and memory in adult male rats

The hippocampus is essentially involved in learning and memory, and is known to be a target for androgen actions. Androgen receptors are densely expressed in CA1 of rat hippocampus, and mediate the effects of testosterone (T) on learning and memory. T depletion or administration can modulate neural function and cognitive performance. We conducted series of experiments to further investigate the effect of castration or intra hippocampal injection of T on acquisition, consolidation and retrieval of inhibitory avoidance learning and memory. Male adult rats were bilaterally cannulated into CA1 of hippocampus, and then received T (1, 10, 20, 40 and 80mug/0.5mul/side) or vehicle (DMSO), 30min before training, immediately after training and 30min before retrieval in inhibitory avoidance task. Castration was made by gonadectomy of male rats and behavioral tests performed 4 weeks later. Our results showed that gonadectomy of male rats did not influence performance on inhibitory avoidance task, as compared to sham-operated rats. We have also found that pre-training, post-training and pre-retrieval intra CA1 injections of T significantly decreased step-through latencies in inhibitory avoidance learning at doses 1 and 80, 20, and 20 and 40mug/0.5mul/side, respectively. The data suggest that intra CA1 administration of T could impair learning and memory acquisition, consolidation and retrieval, while systemic androgen's depletion have no effect on memory, in inhibitory avoidance task.     

Retrograde amnesia: neither partial nor complete hippocampal lesions in rats result in preferential sparing of remote spatial memory, even after reminding

Many lesion experiments have provided evidence that the hippocampus plays a time-limited role in memory, consistent with the operation of a systems-level memory consolidation process during which lasting neocortical memory traces become established [see Squire, L. R., Clark, R. E., & Knowlton, B. J. (2001). Retrograde amnesia. Hippocampus 11, 50]. However, large lesions of the hippocampus at different time intervals after acquisition of a watermaze spatial reference memory task have consistently resulted in temporally ungraded retrograde amnesia [Bolhuis, J. J., Stewart, C. A., Forrest, E. M. (1994). Retrograde amnesia and memory reactivation in rats with ibotenate lesions to the hippocampus or subiculum. Quarterly Journal of Experimental Psychology 47B, 129; Mumby, D. G., Astur, R. S., Weisend, M. P., Sutherland, R. J. (1999). Retrograde amnesia and selective damage to the hippocampal formation: memory for places and object discriminations. Behavioural Brain Research 106, 97; Sutherland, R. J., Weisend, M. P., Mumby, D., Astur, R. S., Hanlon, F. M., et al. (2001). Retrograde amnesia after hippocampal damage: recent vs. remote memories in two tasks. Hippocampus 11, 27]. It is possible that spatial memories acquired during such a task remain permanently dependent on the hippocampus, that chance performance may reflect a failure to access memory traces that are initially unexpressed but still present, or that graded retrograde amnesia for spatial information might only be observed following partial hippocampal lesions. This study examined the retrograde memory impairments of rats that received either partial or complete lesions of the hippocampus either 1-2 days, or 6 weeks after training in a watermaze reference memory task. Memory retention was assessed using a novel 'reminding' procedure consisting of a series of rewarded probe trials, allowing the measurement of both free recall and memory reactivation. Rats with complete hippocampal lesions exhibited stable, temporally ungraded retrograde amnesia, and could not be reminded of the correct location. Partially lesioned rats could be reminded of a recently learned platform location, but no recovery of remote memory was observed. These results offer no support for hippocampus-dependent consolidation of allocentric spatial information, and suggest that the hippocampus can play a long-lasting role in spatial memory. The nature of this role--in the storage, retrieval, or expression of memory--is discussed.