Object recognition memory and the rodent hippocampus

In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR task. Rats received 12 5-min exposures to two identical objects and then received either bilateral lesions of the hippocampus or sham surgery 1 d, 4 wk, or 8 wk after the final exposure. On a retention test 2 wk after surgery, the 1-d and 4-wk hippocampal lesion groups exhibited impaired object recognition memory. In contrast, the 8-wk hippocampal lesion group performed similarly to controls, and both groups exhibited a preference for the novel object. These same rats were then given four postoperative tests using unique object pairs and a 3-h delay between the exposure phase and the test phase. Hippocampal lesions produced moderate and reliable memory impairment. The results suggest that the hippocampus is important for object recognition memory.Recognition memory refers to the ability to judge a previously encountered item as familiar and depends on the integrity of the medial temporal lobe (Squire et al. 2007). Tasks that assess recognition memory (and object recognition memory in particular) have become increasingly useful tools for basic and preclinical research investigating the neural basis of memory (Winters et al. 2008). Perhaps the best known of these tasks is the novel object recognition task (NOR) (also known as the visual paired-comparison task in studies with humans and monkeys).Studies of the NOR task in humans with hippocampal damage (McKee and Squire 1993; Pascalis et al. 2004) and in monkeys with selective damage to the hippocampus (Pascalis and Bachevalier 1999; Zola et al. 2000; Nemanic et al. 2004) have resulted in clear and consistent findings. Damage limited to the hippocampus is sufficient to produce impaired recognition memory (Squire et al. 2007, Box 1). In rats and mice, the NOR task has become particularly popular and is currently a benchmark task for assessing recognition memory. Yet despite its widespread use in rodents, the findings are rather mixed. For example, in the rat, although there is agreement that the perirhinal cortex is critically important for normal NOR performance, there is less agreement about the hippocampus (for review, see Winters et al. 2008). Although some of the discrepancies between studies may be attributed to differences in lesion size and in the length of the retention delay (Broadbent et al. 2004), these factors cannot account for all the findings (Squire et al. 2007).Whereas most studies have investigated the effects of hippocampal lesions on postoperative NOR performance, there is also interest in the effects of hippocampal lesions on memory for previously encountered objects. For a number of tasks, hippocampal lesions produce temporally graded retrograde amnesia, such that memory acquired recently is impaired and memory acquired more remotely is spared (for review, see Squire et al. 2004; Frankland and Bontempi 2005). In the case of the single study of retrograde memory that has involved the NOR task, recognition memory was impaired when a 5-wk interval intervened between training and hippocampal surgery (Gaskin et al. 2003). It remains possible that memory might be spared if a longer delay was imposed between training and surgery.The aim of the present study was to assess both the anterograde and retrograde effects of hippocampal lesions on recognition memory using the NOR task. To thoroughly assess the effects of hippocampal lesions we used (1) large groups of animals, (2) multiple tests of NOR memory, (3) a scoring method that allowed object preference to be determined on a second-by-second basis during the recognition tests, and (4) a novel training protocol that permitted the evaluation of recognition memory even after a retention interval as long as 10 wk.     

On the role of hippocampal protein synthesis in the consolidation and reconsolidation of object recognition memory

Upon retrieval, consolidated memories are again rendered vulnerable to the action of metabolic blockers, notably protein synthesis inhibitors. This has led to the hypothesis that memories are reconsolidated at the time of retrieval, and that this depends on protein synthesis. Ample evidence indicates that the hippocampus plays a key role both in the consolidation and reconsolidation of different memories. Despite this fact, at present there are no studies about the consequences of hippocampal protein synthesis inhibition in the storage and post-retrieval persistence of object recognition memory. Here we report that infusion of the protein synthesis inhibitor anisomycin in the dorsal CA1 region immediately or 180 min but not 360 min after training impairs consolidation of long-term object recognition memory without affecting short-term memory, exploratory behavior, anxiety state, or hippocampal functionality. When given into CA1 after memory reactivation in the presence of familiar objects, ANI did not affect further retention. However, when administered into CA1 immediately after exposing animals to a novel and a familiar object, ANI impaired memory of both of them. The amnesic effect of ANI was long-lasting, did not happen after exposure to two novel objects, following exploration of the context alone, or in the absence of specific stimuli, suggesting that it was not reversible but was contingent on the reactivation of the consolidated trace in the presence of a salient, behaviorally relevant novel cue. Our results indicate that hippocampal protein synthesis is required during a limited post-training time window for consolidation of object recognition memory and show that the hippocampus is engaged during reconsolidation of this type of memory, maybe accruing new information into the original trace.     

The consolidation of object and context recognition memory involve different regions of the temporal lobe

These experiments investigated the involvement of several temporal lobe regions in consolidation of recognition memory. Anisomycin, a protein synthesis inhibitor, was infused into the hippocampus, perirhinal cortex, insular cortex, or basolateral amygdala of rats immediately after the sample phase of object or object-in-context recognition memory training. Anisomycin infused into perirhinal or insular cortices blocked long-term (24 h), but not short-term (90 min) object recognition memory. Infusions into the hippocampus or amygdala did not impair object recognition memory. Anisomycin infused into the hippocampus blocked long-term, but not short-term object-in-context recognition memory, whereas infusions administered into the perirhinal cortex, insular cortex, or amygdala did not affect object-in-context recognition memory. These results clearly indicate that distinct regions of the temporal lobe are differentially involved in long-term object and object-in-context recognition memory. Whereas perirhinal and insular cortices are required for consolidation of familiar objects, the hippocampus is necessary for consolidation of contextual information of recognition memory. Altogether, these results suggest that temporal lobe structures are differentially involved in recognition memory consolidation.     

Reversible hippocampal lesions disrupt water maze performance during both recent and remote memory tests

Conventional lesion methods have shown that damage to the rodent hippocampus can impair previously acquired spatial memory in tasks such as the water maze. In contrast, work with reversible lesion methods using a different spatial task has found remote memory to be spared. To determine whether the finding of spared remote spatial memory depends on the lesion method, we reversibly inactivated the hippocampus with lidocaine either immediately (0-DAY) or 1 mo (30-DAY) after training in a water maze. For both the 0-DAY and 30-DAY retention tests, rats that received lidocaine infusions exhibited impaired performance. In addition, when the 0-DAY group was retested 2 d later, (when the drug was no longer active), the effect was reversed. That is, rats that had previously received lidocaine performed as well as control rats did. These findings indicate that the rodent hippocampus is important for both recent and remote spatial memory, as assessed in the water maze. What determines whether remote spatial memory is preserved or impaired following disruption of hippocampal function appears to be the type of task used to assess spatial memory, not the method used to disrupt the hippocampus.     

Post-training reversible inactivation of the hippocampus enhances novel object recognition memory

Research on the role of the hippocampus in object recognition memory has produced conflicting results. Previous studies have used permanent hippocampal lesions to assess the requirement for the hippocampus in the object recognition task. However, permanent hippocampal lesions may impact performance through effects on processes besides memory consolidation including acquisition, retrieval, and performance. To overcome this limitation, we used an intrahippocampal injection of the GABA agonist muscimol to reversibly inactivate the hippocampus immediately after training mice in two versions of an object recognition task. We found that the inactivation of the dorsal hippocampus after training impairs object-place recognition memory but enhances novel object recognition (NOR) memory. However, inactivation of the dorsal hippocampus after repeated exposure to the training context did not affect object recognition memory. Our findings suggest that object recognition memory formation does not require the hippocampus and, moreover, that activity in the hippocampus can interfere with the consolidation of object recognition memory when object information encoding occurs in an unfamiliar environment.The medial temporal lobe plays an important role in recognition memory formation, as damage to this brain structure in humans, monkeys, and rodents impairs performance in recognition memory tasks (for review, see Squire et al. 2007). Within the medial temporal lobe, studies have consistently demonstrated that the perirhinal cortex is involved in this form of memory (Brown and Aggleton 2001; Winters and Bussey 2005; Winters et al. 2007, 2008; Balderas et al. 2008). In contrast, the role of the hippocampus in object recognition memory remains a source of debate. Some studies have reported novel object recognition (NOR) impairments in animals with hippocampal lesions (Clark et al. 2000; Broadbent et al. 2004, 2010), yet others have reported no impairments (Winters et al. 2004; Good et al. 2007). Differences in hippocampal lesion size and behavioral procedures among the different studies have been implicated as the source of discrepancy in these findings (Ainge et al. 2006), but previous studies have not examined the consequences of environment familiarity on the hippocampus dependence of object recognition memory.Previous studies addressing the role of the hippocampus in recognition memory relied on permanent, pre-training lesions (Clark et al. 2000; Broadbent et al. 2004; Winters et al. 2004; Good et al. 2007). Permanent lesions inactivate the hippocampus not only during the consolidation phase, but also during habituation, acquisition, and memory retrieval, potentially confounding interpretation of the results. Furthermore, permanent lesion studies require long surgery recovery times during which extrahippocampal changes may emerge to mask or compensate for the loss of hippocampal function. To overcome these problems, we reversibly inactivated the dorsal hippocampus after training mice in two versions of the object recognition task. We infused muscimol, a γ-aminobutyric acid (GABA) receptor type A agonist, into the dorsal hippocampus immediately after training in an object-place recognition task or immediately following training in a NOR task. Consistent with previous studies (Save et al. 1992; Galani et al. 1998; Mumby et al. 2002; Stupien et al. 2003; Aggleton and Brown 2005), we observed that hippocampal inactivation impairs object-place recognition memory. Interestingly, we observed that the degree of contextual familiarity can influence NOR memory formation. We found that when shorter periods of habituation to the experimental environment were used, hippocampal inactivation enhances long-term NOR memory. In contrast, after extended periods of contextual habituation, long-term recognition memory was unaltered by hippocampal inactivation. Together these results suggest that if familiarization with objects occurs at a stage in which the contextual environment is relatively novel, the hippocampus plays an inhibitory role on the consolidation of object recognition memory. Supporting this view, we observed that object recognition memory is unaffected by hippocampal inactivation when initial exploration of the objects occurred in a familiar environment.     

Impaired odor recognition memory in patients with hippocampal lesions

In humans, impaired recognition memory following lesions thought to be limited to the hippocampal region has been demonstrated for a wide variety of tasks. However, the importance of the human hippocampus for olfactory recognition memory has scarcely been explored. We evaluated the ability of memory-impaired patients with damage thought to be limited to the hippocampal region to recognize a list of odors. The patients were significantly impaired after a retention delay of 1 h. Olfactory sensitivity was intact. This finding is in agreement with earlier reports that rats with hippocampal lesions exhibited memory impairment on an odor delayed nonmatching to sample task (after 30 min and 1 h) and that patients with damage thought to be limited to the hippocampal region were impaired on an odor span memory task. Olfactory recognition memory, similar to recognition memory in other sensory modalities, depends on the integrity of the hippocampal region.     

The effects of lesions to the rat hippocampus or rhinal cortex on olfactory and spatial memory: retrograde and anterograde findings

The role of the hippocampal system in retrograde and anterograde amnesia was investigated by using a novel olfactory-guided paradigm and a traditional test of spatial learning. In the retrograde study, rats were trained on a sequence of two-choice olfactory discriminations in the weeks prior to receiving neurotoxic lesions of the hippocampus or aspiration lesions of the perirhinal-entorhinal cortex. Memory tests for preoperatively learned discriminations revealed no statistical impairment for subjects with damage to the hippocampus on a problem learned remote in time from surgery (i.e., 4 weeks +) or on the two recently learned discriminations (i.e., 1–3 weeks prior to surgery). The performance of subjects with perirhinal-entorhinal damage provided an important comparison for subjects with specific hippocampal lesions. Despite showing intact memory for the remotely learned problem, perirhinalentorhinal damage resulted in numerically (although not significantly) weaker performance on postoperative tests of retention for the discriminations learned in the 3 weeks prior to surgery. In the anterograde portion of the study, long-term memory for newly acquired discriminations was spared in subjects with damage to the hippocampus, whereas subjects in the perirhinal-entorhinal lesion group again showed the weakest memory performance on these tests of 5-day retention. Postoperative water maze learning was uniformly impaired in subjects with damage to the hippocampus and perirhinalentorhinal cortex, thus confirming the effect of these lesions and supporting the involvement of these brain areas in spatial processes. These findings further dissociate the specific involvement of the hippocampus in tasks of a spatial-relational nature versus nonrelational tasks, such as discrimination learning and recognition memory (e.g., Duva et al., 1997; Eichenbaum, 1997; Eichenbaum, Schoenbaum, Young, & Bunsey, 1996). Moreover, the results suggest that damage to the hippocampus itself does not contribute to retrograde or anterograde memory impairments for all types of information, whereas the data suggest a more important role for the perirhinal-entorhinal cortex in recognition memory, irrespective of modality.     

A secreted form of the beta-amyloid precursor protein (sAPP695) improves spatial recognition memory in OF1 mice

The beta-amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD) and appears to be a multifunctional protein. Secreted forms of APP (sAPP) have memory-enhancing effects in certain behavioral paradigms. To investigate sAPP's role in spatial memory processes, we adapted a spatial recognition task and evaluated (1) the performance of OF1 mice after massed training (single 15-min acquisition session) and distributed training (three 5-min acquisition sessions), (2) the decline of spatial recognition performance by introducing different delays (5min, 1, 3, and 24h) between the acquisition and retention phases, and (3) the effects of sAPP(695) on spatial recognition memory. In the present study, mice selectively reacted to a change in the spatial configuration of five objects. Indeed, 3min post-acquisition, mice performed similarly in the massed and distributed versions of the task, by re-exploring the two displaced objects only, whereas mice exposed to the same spatial configuration did not. Additionally, all mice did react to a novel object in a subsequent object recognition phase. Mice detected object displacements 5min, 1h, or 3h post-acquisition, but no more at a 24h-delay. Finally, mice treated with sAPP(695) intracerebroventricularly at a dose of 0.5pg/4microL/mouse, 20-min pre-acquisition or 5-min post-acquisition, still reacted to a spatial change in objects position 24h post-acquisition, in marked contrast to NaCl-treated mice. Our data demonstrate that sAPP(695) significantly improves a form of spatial memory, and confirms the hypothesis of an action of this protein on early memory processes.     

On the participation of mTOR in recognition memory

Evidence indicates that activation of the neuronal protein synthesis machinery is required in areas of the brain relevant to memory for consolidation and persistence of the mnemonic trace. Here, we report that inhibition of hippocampal mTOR, a protein kinase involved in the initiation of mRNA translation, immediately or 180min but not 540min after training impairs consolidation of long-term object recognition memory without affecting short-term memory retention or exploratory behavior. When infused into dorsal CA1 after long-term memory reactivation in the presence of familiar objects the mTOR inhibitor rapamycin (RAP) did not affect retention. However, when given immediately after exposing animals to a novel and a familiar object, RAP impaired memory for both of them. The amnesic effect of the post-retrieval administration of RAP was long-lasting, did not happen after exposure to two novel objects or following exploration of the training arena in the absence of other stimuli, suggesting that it was contingent with reactivation of the consolidated trace in the presence of a behaviorally relevant and novel cue. Our results indicate that mTOR activity is required in the dorsal hippocampus for consolidation of object recognition memory and suggest that inhibition of this kinase after memory retrieval in the presence of a particular set of cues hinders persistence of the original recognition memory trace.     

Role of the dorsal hippocampus in object memory load

The dorsal hippocampus is crucial for mammalian spatial memory, but its exact role in item memory is still hotly debated. Recent evidence in humans suggested that the hippocampus might be selectively involved in item short-term memory to deal with an increasing memory load. In this study, we sought to test this hypothesis. To this aim we developed a novel behavioral procedure to study object memory load in mice by progressively increasing the stimulus set size in the spontaneous object recognition task. Using this procedure, we demonstrated that naive mice have a memory span, which is the number of elements they can remember for a short-time interval, of about six objects. Then, we showed that excitotoxic selective lesions of the dorsal hippocampus did not impair novel object discrimination in the condition of low memory load. In contrast, the same lesion impaired novel object discrimination in the high memory load condition, and reduced the object memory span to four objects. These results have important heuristic and clinical implications because they open new perspective toward the understanding of the role of the hippocampus in item memory and in memory span deficits occurring in human pathologies, such as Alzheimer's disease and schizophrenia.     

Posttraining activation of CB1 cannabinoid receptors in the CA1 region of the dorsal hippocampus impairs object recognition long-term memory

Evidence indicates that brain endocannabinoids are involved in memory processing. However, the participation of CB1 and CB2 cannabinoid receptors in recognition memory has not been yet conclusively determined. Therefore, we evaluated the effect of the posttraining activation of hippocampal cannabinoid receptors on the consolidation of object recognition memory. Rats with infusion cannulae stereotaxically aimed to the CA1 region of the dorsal hippocampus were trained in an object recognition learning task involving exposure to two different stimulus objects. Memory retention was assessed at different times after training. In the test sessions, one of the objects presented during training was replaced by a novel one. When infused in the CA1 region immediately after training, the non-selective cannabinoid receptor agonist WIN-55,212-2 and the endocannabinoid membrane transporter inhibitor VDM-11 blocked long-term memory retention in a dose-dependent manner without affecting short-term memory, exploratory behavior, anxiety state or the functionality of the hippocampus. The amnesic effect of WIN-55,212-2 and VDM-11 was not due to state-dependency and was completely reversed by co-infusion of the CB1 receptor antagonist AM-251 and mimicked by the CB1 receptor agonist ACEA but not by the CB2 receptor agonists JWH-015 and palmitoylethanolamide. Our data indicate that activation of hippocampal CB1 receptors early after training hampers consolidation of object recognition memory.     

Muscarinic receptors activity in the perirhinal cortex and hippocampus has differential involvement in the formation of recognition memory

In this work we probed the effects of post-trial infusions of the muscarinic receptor antagonist scopolamine on object recognition memory formation. Scopolamine was infused bilaterally immediately after the sample phase in the perirhinal cortex or dorsal hippocampus and animals were tested for short-term (90 min) or long-term (24 h) memory. Results showed that scopolamine impaired short-term memory when injected in either the perirhinal cortex or hippocampus. Nevertheless, scopolamine disrupted long-term memory when administrated in the perirhinal cortex but not when applied in the hippocampus. Long-term memory was unaffected when scopolamine was infused 160 min after the sample phase or 90 min before test phase. Our data indicate that short-term recognition memory requires muscarinic receptors signaling in both the perirhinal cortex and hippocampus, whereas long-term recognition memory depends on muscarinic receptors in the perirhinal cortex but not hippocampus. These results support a differential involvement of muscarinic activity in these two medial temporal lobe structures in the formation of recognition memory.     

Posttraining inactivation of excitatory afferent input to the locus coeruleus impairs retention in an inhibitory avoidance learning task

These experiments examined whether the nucleus paragigantocellularis (PGi) contributes to memory storage processing via its ascending excitatory influence on locus coeruleus (LC) neuronal activity. Activation of the LC leads to memory enhancement and also results in a widespread release of norepinephrine in target structures, such as the amygdala and hippocampus. Infusion of norepinephrine into either structure also improves memory for several types of learned responses. Thus, the capacity for norepinephrine to modulate memory within limbic structures may be contingent upon the functional connections between PGi and the LC. To examine this hypothesis, male Sprague-Dawley rats were implanted with cannula aimed above PGi (Experiments 1 and 2) or 1.5 mm dorsal or medial to PGi (Experiment 3). Immediately following inhibitory avoidance training (0.45 mA, 0. 5 s), phosphate-buffered saline, lidocaine (Experiment 1), or 12.5 or 25 nmol/0.5 microl of the GABA agonist muscimol (Experiment 2) was infused into PGi. On a retention test given 48 h later, the latency to reenter the footshock compartment was significantly shorter for subjects given either lidocaine or 12.5 or 25.0 nmol of muscimol compared to controls. In Experiment 3, infusion of lidocaine or muscimol into areas 1.5 mm dorsal or medial to PGi did not significantly alter retention, indicating that the memory impairment observed in Experiments 1 and 2 was site specific and not due to the spread of drug to cell groups surrounding PGi. These findings suggest that PGi may serve a vital function in relaying biologically relevant information to forebrain structures involved in memory via its excitatory influence on the LC.     

Hippocampal infusions of glucose reverse memory deficits produced by co-infusions of a GABA receptor agonist

Although septal infusions of glucose typically have positive effects on memory, we have shown repeatedly that this treatment exacerbates memory deficits produced by co-infusions of gamma-aminobutyric acid (GABA) receptor agonists. The present experiments tested whether this negative interaction between glucose and GABA in the medial septum would be observed in the hippocampus, a brain region where glucose typically has positive effects on memory. Specifically, we determined whether hippocampal infusions of glucose would reverse or exacerbate memory deficits produced by hippocampal co-infusions of the GABA receptor agonist muscimol. Fifteen minutes prior to either assessing spontaneous alternation (SA) or continuous multiple trial inhibitory avoidance (CMIA) training, male Sprague-Dawley-derived rats were given bilateral hippocampal infusions of vehicle (phosphate-buffered saline [PBS], 1 microl/2 min), glucose (33 or 50 nmol), muscimol (0.3 or 0.4 microg, SA or 3 microg, CMIA) or muscimol and glucose combined in one solution. The results indicated that hippocampal infusions of muscimol alone decreased SA scores and CMIA retention latencies. More importantly, hippocampal infusions of glucose, at doses that had no effect when infused alone, attenuated (33 nmol) or reversed (50 nmol) the muscimol-induced memory deficits. Thus, although co-infusions of glucose with muscimol into the medial septum impair memory, the present findings show that an opposite effect is observed in the hippocampus. Collectively, these findings suggest that the memory-impairing interaction between glucose and GABA in the medial septum is not a general property of the brain, but rather is brain region-dependent.     

Evidence for the substantia nigra pars compacta as an essential component of a memory system independent of the hippocampal memory system

The aim of the present study was to test if the nigrostriatal pathway is an essential component for a water maze cued task learning and if it works independently of the hippocampal memory system. This hypothesis was tested using an animal model of Parkinson's disease in which male Wistar rats were lesioned in the substantia nigra pars compacta (SNc) by the intranigral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), thus causing a partial depletion of striatal dopamine. SNc-lesioned and sham-operated animals were implanted bilaterally with guide cannulae above the dorsal hippocampus in order to be tested after the administration of 0.4 microl 2% lidocaine or saline into this structure. The animals were tested in a spatial or in a cued version of the water maze, memory tasks previously reported to model hippocampal-dependent spatial/relational and striatal-dependent S-R learning, respectively. Hippocampal inactivation, but not SNc lesion, impaired learning and memory in the spatial version of the water maze. An opposite situation was observed with the cued version. No significant interaction was observed between the SNc lesion and hippocampal inactivation conditions affecting scores in the spatial or in the cued version of the water maze. These results suggest that the nigrostriatal pathway is an essential part of the memory system that processes S-R learning and that it works independently of the hippocampal memory system that processes spatial/relational memories.     

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.     

Scopolamine infused into perirhinal cortex improves object recognition memory by blocking the acquisition of interfering object information

In a previous study, we reported apparently paradoxical facilitation of object recognition memory following infusions of the cholinergic muscarinic receptor antagonist scopolamine into the perirhinal cortex (PRh) of rats. We attributed these effects to the blockade by scopolamine of the acquisition of interfering information. The present study tested this possibility directly by modifying the spontaneous object recognition memory task to allow the presentation of a potentially interfering object either before the sample phase or in the retention delay between the sample and choice phases. Presentation of an object between the sample and choice phases disrupted subsequent recognition of the sample object (retroactive interference), and intra-PRh infusions of scopolamine prior to the presentation of the irrelevant object prevented this retroactive interference effect. Moreover, presentation of an irrelevant object prior to the sample phase interfered proactively with sample object recognition, and intra-PRh infusions of scopolamine prior to the presentation of the pre-sample object prevented this proactive interference effect. These results suggest that blocking muscarinic cholinergic receptors in PRh can disrupt the acquisition of potentially interfering object information, thereby facilitating object recognition memory. This finding provides further, strong evidence that acetylcholine is important for the acquisition of object information in PRh.     

Contrasting hippocampal and perirhinal cortex function using immediate early gene imaging.

The perirhinal cortex and hippocampus have close anatomical links, and it might, therefore, be predicted that they have close, interlinked roles in memory. Lesion studies have, however, often failed to support this prediction, providing dissociations and double dissociations between the two regions on tests of object recognition and spatial memory. In a series of rat studies we have compared these two regions using the expression of the immediate early gene c-fos as a marker of neuronal activity. This gene imaging approach makes it possible to assess the relative involvement of different brain regions and avoids many of the limitations of the lesion approach. A very consistent pattern of results was found as the various hippocampal subfields but not the perirhinal cortex show increased c-fos activity following tests of spatial learning. In contrast, the perirhinal cortex but none of the hippocampal subfields show increased c-fos activity when presented with novel rather than familiar visual objects. When novel scenes are created by the spatial rearrangement of familiar objects it is the hippocampus and not the perirhinal cortex that shows c-fos changes. This double dissociation for gene expression accords with that found from lesion studies and highlights the different contributions of the perirhinal cortex and hippocampus to memory.     

Contrasting hippocampal and perirhinalcortex function using immediate early gene imaging

The perirhinal cortex and hippocampus have close anatomical links, and it might, therefore, be predicted that they have close, interlinked roles in memory. Lesion studies have, however, often failed to support this prediction, providing dissociations and double dissociations between the two regions on tests of object recognition and spatial memory. In a series of rat studies we have compared these two regions using the expression of the immediate early gene c-fosas a marker of neuronal activity. This gene imaging approach makes it possible to assess the relative involve-ment of different brain regions and avoids many of the limitations of the lesion approach. A very consistent pattern of results was found as the various hippocampal subfields but not the peri-rhinal cortex show increased c-fosactivity following tests of spatial learning. In contrast, the perirhinal cortex but none of the hippocampal subfields show increased c-fosactivity when presented with novel rather than familiar visual objects. When novel scenes are created by the spatial rearrangement of familiar objects it is the hippocampus and not the perirhinal cortex that shows c-foschanges. This double dissociation for gene expression accords with that found from lesion studies and highlights the different contributions of the perirhinal cortex and hippocampus to memory.