Extensive lesions of cholinergic basal forebrain neurons do not impair spatial working memory

A recent studysuggests that lesions to all major areas of the cholinergic basal forebrain in the rat (medial septum, horizontal limb of the diagonal band of Broca, and nucleus basalis magnocellularis) impair a spatial working memory task. However, this experiment used a surgical technique that mayhave damaged cerebellar Purkinje cells. The present studytested rats with highlyselective lesions of cholinergic neurons in all major areas of the basal forebrain on a spatial working memorytask in the radial arm maze. In postoperative testing, there were no significant differences between lesion and control groups in working memory, even with a delayperiod of 8 h, with the exception of a transient impairment during the first 2 d of postoperative testing at shorter delays (0 or 2 h). This finding corroborates other results that indicate that the cholinergic basal forebrain does not playa significant role in spatial working memory. Furthermore, it underscores the presence of intact memoryfunctions after cholinergic basal forebrain damage, despite attentional impairments that follow these lesions, demonstrated in other task paradigms.     

Electrolytic lesions of dorsal CA3 impair episodic-like memory in rats

Episodic memory is the ability to recollect one's past experiences occurring in an unique spatial and temporal context. In non-human animals, it is expressed in the ability to combine "what", "where" and "when" factors to form an integrated memory system. During the search for its neural substrates, the hippocampus has attracted a lot of attentions. Yet, it is not yet possible to induce a pure episodic-like memory deficit in animal studies without being confounded by impairments in the spatial cognition. Here, we present a lesion study evidencing direct links between the hippocampus CA3 region and the episodic-like memory in rats. In a spontaneous object exploration task, lesioned rats showed no interaction between the temporal and spatial elements in their memory associated with the objects. In separate tests carried out subsequently, the same animals still expressed abilities to process spatial, temporal, and object recognition memory. In conclusions, our results support the idea that the hippocampus CA3 has a particular status in the neural mechanism of the episodic-like memory system. It is responsible for combining information from different modules of cognitive processes.     

Inferior temporal lesions do not impair discrimination of rotated patterns in monkeys.

Ablation of inferior temporal cortex in the rhesus monkey produces a visual discrimination learning deficit. The severity of this deficit has often been found to be a function of task difficulty. This report concerns a type of visual discrimination problem that, although difficult, is not sensitive to inferior temporal lesions. Monkeys with anterior, posterior, and complete inferior temporal lesions were repeatedly unimpaired or only slightly impaired in learning to discriminate a pattern from the same pattern rotated 90 degrees or 180 degrees; yet they were very severely impaired in learning equally or more difficult discriminations of two different patterns. This demonstration that discrimination of orientation of patterns is relatively spared after inferior temporal lesions helps specify the pattern-recognition processes that require inferior temporal cortex.     

Basolateral amygdala lesions do not prevent memory of context-footshock training

The present studies examined the effects of basolateral amygdala (BLA) lesions induced prior to or after context-footshock training on 48-h memory, using several retention measures. In experiment 1, male Sprague-Dawley rats with bilateral BLA lesions (NMDA, 12.5 mg/mL, 0.2 μL) were given footshock training in one compartment of a two-compartment alley. Rats were habituated to the alley and 24 h later were given two footshocks in the shock compartment. Retention was tested 48 h later, using latency to enter the shock compartment and time spent freezing as measures of memory. Two days later, they were tested again and received a footshock on each re-entry of the shock compartment prior to remaining in the safe compartment for 200 consecutive seconds. The BLA lesions did not block retention as assessed by freezing or number of re-entries of the shock compartment. In experiment 2, no prior habituation was given, and only one footshock was used for the training. BLA lesions did not block retention, as indicated by latencies to enter the shock compartment on a 48-h test or by number of entries of the shock compartment. Experiment 3 examined the effects of the GABA_A agonist muscimol infused into the BLA prior to the 48-h retention test. The muscimol infusions decreased retention test entrance latencies but did not block retention as assessed by the number of subsequent entries of the shock compartment. These findings provide additional evidence that an intact BLA is not required for the acquisition or retention of context-footshock training.     

Social enrichment improves social recognition memory in male rats

The social environment is thought to have a strong impact on cognitive functions. In the present study, we investigated whether social enrichment could affect rats’ memory ability using the “Different Objects Task (DOT),” in which the levels of memory load could be modulated by changing the number of objects to be remembered. In addition, we applied the DOT to a social discrimination task using unfamiliar conspecific juveniles instead of objects. Animals were housed in one of the three different housing conditions after weaning [postnatal day (PND) 21]: social-separated (1 per cage), standard (3 per cage), or social-enriched (10 per cage) conditions. The object and social recognition tasks were conducted on PND 60. In the sample phase, the rats were allowed to explore a field in which 3, 4, or 5 different, unfamiliar stimuli (conspecific juveniles through a mesh or objects) were presented. In the test phase conducted after a 5-min delay, social-separated rats were able to discriminate the novel conspecific from the familiar ones only under the condition in which three different conspecifics were presented; social-enriched rats managed to recognize the novel conspecific even under the condition of five different conspecifics. On the other hand, in the object recognition task, both social-separated and social-enriched rats were able to discriminate the novel object from the familiar ones under the condition of five different objects. These results suggest that social enrichment can enhance social, but not object, memory span.     

Selective fimbria and thalamic lesions differentially impair forms of working memory in rats.

Several series of experiments were designed to compare the effects of selective lesions of the fimbria or of thalamic nuclei on three different tasks involving working memory in rats: object recognition, place recognition, and the radial arm maze test. The main effects of fimbria lesions were as follows: they produced deficits in the radial maze; object recognition was spared or even facilitated, whereas place recognition was impaired. Electrolytic lesions of either centromedian-parafascicularis (CM-Pf) or dorsomedialis (DM) nuclei produced highly significant deficits in the radial maze test but spared object and place recognition. Ibotenate lesions of the CM-Pf had no effect on any test, which means that the critical structure in the effects of the electrolytic lesions of the CM-Pf was the fasciculus retroflexus (FR). These data may contribute two main points to animal models of hippocampal and thalamic amnesia: (1) different forms of working memory in rats might have different neural bases and (2) the FR may be involved in learning and memory processes.     

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.     

Chronic, severe hypertension does not impair spatial learning and memory in Sprague-Dawley rats

This study tested the hypothesis that long-term hypertension impairs spatial learning and memory in rats. In 6-wk-old Sprague-Dawley rats, chronic hypertension was induced by placing one of three sizes of stainless steel clips around the descending aorta (above the renal artery), resulting in a 20–80-mm Hg increase of arterial pressure in all arteries above the clip, that is, the upper trunk and head. Ten months later, the rats were tested for 5 d in a repeated-acquisition water maze task, and on the fifth day, they were tested in a probe trial; that is, there was no escape platform present. At the end of the testing period, the nonsurgical and sham control groups had similar final escape latencies (16±4 sec and 23±9 sec, respectively) that were not significantly different from those of the three hypertensive groups. Rats with mild hypertension (140–160 mm Hg) had a final escape latency of 25±6 sec, whereas severely hypertensive rats (170–199 mm Hg) had a final escape latency of 21±7 sec and extremely hypertensive rats (>200 Hg) had a final escape latency of 19±5 sec. All five groups also displayed a similar preference for the correct quadrant in the probe trial. Together, these data suggest that sustained, severe hypertension for over 10 mo is not sufficient to impair spatial learning and memory deficits in otherwise normal rats.     

Alcohol beverage cues impair memory in high social drinkers

This study examined the influence of an alcohol beverage cue on memory processes in social drinkers. High and low drinking college students viewed a series of 15 pictures of common objects with the eighth picture either of an alcohol beverage or a soda. For high drinkers, free recall of the alcohol picture was enhanced, and memory for the pictures immediately following the cue was suppressed, relative to the series containing the soda picture. No such effects were observed for light drinkers. Apparently, alcohol cues affect attention and memory in heavy social drinkers. These results have important implications for theories of memory and attention, for explanations of addictive behaviour, and for effective prevention and treatment of alcoholism.     

Inferior colliculus lesions impair eyeblink conditioning in rats

The neural plasticity necessary for acquisition and retention of eyeblink conditioning has been localized to the cerebellum. However, the sources of sensory input to the cerebellum that are necessary for establishing learning-related plasticity have not been identified completely. The inferior colliculus may be a source of sensory input to the cerebellum through its projection to the medial auditory thalamus. The medial auditory thalamus is necessary for eyeblink conditioning in rats and projects to the lateral pontine nuclei, which then project to the cerebellar nuclei and cortex. The current experiment examined the role of the inferior colliculus in auditory eyeblink conditioning. Rats were given bilateral or unilateral (contralateral to the conditioned eye) lesions of the inferior colliculus prior to 10 d of delay eyeblink conditioning with a tone CS. Rats with bilateral or unilateral lesions showed equivalently impaired acquisition. The extent of damage to the contralateral inferior colliculus correlated with several measures of conditioning. The findings indicate that the contralateral inferior colliculus provides auditory input to the cerebellum that is necessary for eyeblink conditioning.     

Retrograde amnesia and memory reactivation in rats with ibotenate lesions to the hippocampus or subiculum

The retrograde effects of hippocampal lesions on spatial memory were studied. Rats were given a series of 48 place-navigation trials in an open-field water-maze followed, either 3 days or 14 weeks later, by ibotenic acid lesions of the hippocampus (HPC) or subiculum (SUB), or by sham-surgery (SHAM). Two weeks after surgery they were given a retention test without a hidden escape platform. There was a significant decline in performance with time in the SHAM group, but with the 14-week SHAM group performing significantly better than chance levels, whereas both lesioned groups performed at chance at both retention intervals. All rats were then retrained for 24 trials. SHAM rats escaped rapidly within 2 trials, suggesting a reactivation of memory rather than relearning. The HPC groups were severely impaired during retraining, with a developing trend towards better performance in the 3-day group. After 24 trials of training with the escape platform placed in the opposite quadrant of the pool, this new location was learned successfully by SHAM and SUB rats, but not by HPC rats. These results indicate that selective hippocampal formation lesions can cause deficits in retrieval but do not reveal a time-dependent gradient of memory consolidation.     

Forgotten but not gone: context effects on recognition do not require explicit memory for context

Context effects on recognition memory provide an important indirect assay of associative learning and source memory. Neuropsychological studies have indicated that such context effects may obtain even if the contexts themselves are not remembered--for example, in individuals impaired on direct tests of memory for contextual information. In contrast, a recent study indicated that the effects of temporal context reinstatement on visual recognition obtain only when the contextual information itself was explicitly recollected. Here we report that the effects of reinstatement of spatial-simultaneous context on visual object recognition memory obtain irrespective of whether those context stimuli are explicitly recognized. We suggest that spatial-simultaneous context effects might be based on ensemble unitization of target and context stimuli at encoding, whereas temporal context effects may require recollective processes.     

Forgotten but not gone: Context effects on recognition do not require explicit memory for context

Context effects on recognition memory provide an important indirect assay of associative learning and source memory. Neuropsychological studies have indicated that such context effects may obtain even if the contexts themselves are not remembered—for example, in individuals impaired on direct tests of memory for contextual information. In contrast, a recent study indicated that the effects of temporal context reinstatement on visual recognition obtain only when the contextual information itself was explicitly recollected. Here we report that the effects of reinstatement of spatial-simultaneous context on visual object recognition memory obtain irrespective of whether those context stimuli are explicitly recognized. We suggest that spatial-simultaneous context effects might be based on ensemble unitization of target and context stimuli at encoding, whereas temporal context effects may require recollective processes.     

On the delay-dependent involvement of the hippocampus in object recognition memory

The role of the hippocampus in object recognition memory processes is unclear in the current literature. Conflicting results have been found in lesion studies of both primates and rodents. Procedural differences between studies, such as retention interval, may explain these discrepancies. In the present study, acute lidocaine administration was used to temporarily inactivate the hippocampus prior to training in the spontaneous object recognition task. Male C57BL/6J mice were administered bilateral lidocaine (4%, 0.5 microl/side) or aCSF (0.5 microl/side) directly into the CA1 region of the dorsal hippocampus 5 min prior to sample object training, and object recognition memory was tested after a short ( 5 min) or long (24 h) retention interval. There was no effect of intra-hippocampal lidocaine on the time needed for mice to accumulate sample object exploration, suggesting that inactivation of the hippocampus did not affect sample session activity or the motivation to explore objects. Lidocaine-treated mice exhibited impaired object recognition memory, measured as reduced novel object preference, after a 24 h but not a 5 min retention interval. These data support a delay-dependent role for the hippocampus in object recognition memory, an effect consistent with the results of hippocampal lesion studies conducted in rats. However, these data are also consistent with the view that the hippocampus is involved in object recognition memory regardless of retention interval, and that object recognition processes of parahippocampal structures (e.g., perirhinal cortex) are sufficient to support object recognition memory over short retention intervals.     

Motor interference does not impair the memory consolidation of imagined movements

The present study aimed to investigate whether an interference task might impact the sleep-dependent consolidation process of a mentally learned sequence of movements. Thirty-two participants were subjected to a first training session through motor imagery (MI) or physical practice (PP) of a finger sequence learning task. After 2 h, half of the participants were requested to perform a second interfering PP task (reversed finger sequence). All participants were finally re-tested following a night of sleep on the first finger sequence. The main findings revealed delayed performance gains following a night of sleep in the MI group, i.e. the interfering task did not alter the consolidation process, by contrast to the PP group. These results confirm that MI practice might result in less retroactive interference than PP, and further highlight the relevance of the first night of sleep for the consolidation process following MI practice. These data might thus contribute to determine in greater details the practical implications of mental training in motor learning and rehabilitation.     

Response biases do not underlie the radial maze deficit in rats with mediodorsal thalamus lesions

Previous results indicating that radial maze performance in animals with mediodorsal thalamic lesions is deficient cannot exclude the possibility that these impairments are due to altered motor mechanisms (response biases). The present study sought to eliminate this potentially confounding variable by using a procedure which tests memory for serial position. This procedure involved experimenter-controlled arm entry (number and order) on a radial arm maze. Following this sequence, animals were presented with one previously entered arm along with an arm not yet visited on that trial. Avoidance of the previously entered arm constituted memory for the prior sequence. Thus, this task represents a form of a win-shift or nonmatching-to-sample task. Seven animals were given ibotenic acid lesions of the mediodorsal nucleus and nine others were given sham operations; 2 weeks later testing in the above procedure was conducted. Results indicated that, although control subjects could differentiate between entered and unentered arms without difficulty, animals with lesions were unable to exhibit this distinction. Much of their memory for arms previously entered in a sequence was at chance level, regardless of the placement of the tested arm in the sequence. Some tendency toward increased errors with longer sequences of arm entries was noted. This may indicate that animals with lesions were susceptible to proactive interference from previous choices. Regardless, even without the opportunity to develop or exhibit response biases, animals lesioned in the mediodorsal nucleus were unable to perform this win-shift task reliably. Thus, discrimination among maze arms is impaired after lesion of the mediodorsal nucleus and this impairment is independent of the motor response patterns which emerge during solution of a conventional radial maze task.     

Lipopolysaccharide-induced experimental immune activation does not impair memory functions in humans

Reconsolidation studies have led to the hypothesis that memory, when labile, would be modified in order to incorporate new information. This view has reinstated original propositions suggesting that short-term memory provides the organism with an opportunity to evaluate and rearrange information before storing it, since it is concurrent with the labile state of consolidation. The Chasmagnathus associative memory model is used here to test whether during consolidation it is possible to change some attribute of recently acquired memories. In addition, it is tested whether these changes in behavioral memory features can be explained as modifications on the consolidating memory trace or as a consequence of a new memory trace. We show that short-term memory is, unlike long-term memory, not context specific. During this short period after learning, behavioral memory can be updated in order to incorporate new contextual information. We found that, during this period, the cycloheximide retrograde amnesic effect can be reverted by a single trial in a new context. Finally, by means of memory sensitivity to cycloheximide during consolidation and reconsolidation, we show that the learning of a new context (CS) during this short-term memory period builds up a new memory trace that sustains the behavioral memory update.     

Excitotoxic lesions restricted to the dorsal CA1 field of the hippocampus impair spatial memory and extinction learning in C57BL/6 mice

Recent studies in patients with hippocampal lesions have indicated that the degree of memory impairment is proportional to the extent of damage within the hippocampus. Particularly, patients with damage restricted to the CA1 field demonstrate moderate to severe anterograde amnesia with only slight retrograde amnesia. Comparable results are also seen in other species such as non-human primates and rats; however, the effect of selective damage to CA1 has not yet been characterized in mice. In the present study, we investigated the effects of excitotoxic (NMDA) lesions of dorsal CA1 on several aspects of learning and memory performance in mice. Our data indicate that dorsal CA1 lesioned mice are hyperactive upon exposure to a novel environment, have spatial working memory impairments in the Y-maze spontaneous alternation task, and display deficits in an 8-arm spatial discrimination learning task. Lesioned mice are able to acquire an operant lever-press task but demonstrate extinction learning deficits in this appetitive operant paradigm. Taken together, our results indicate that lesions to dorsal CA1 in mice induce selective learning and memory performance deficits similar to those observed in other species, and extend previous findings indicating that this region of the hippocampus is critically involved in the processing of spatial information and/or the processing of inhibitory responses.     

Electrolytic lesions of the medial prefrontal cortex do not interfere with long-term memory of extinction of conditioned fear

Lesion studies indicate that rats without the medial prefrontal cortex (mPFC) have difficulty recalling fear extinction acquired the previous day. Several electrophysiological studies have also supported this observation by demonstrating that extinction-related increases in neuronal activity in the mPFC participate in expression of fear extinction. However, a more recent study has shown that fear extinction can be recalled, in certain circumstances, without mPFC potentiation, suggesting contribution of other circuits. Here, we examined this possibility in rats that were subjected to auditory fear conditioning, extinction training, and extinction retention test 7 d later. Electrolytic lesions were made in the mPFC, the motor cortex (MO), the dorsal septum (SEP), or the mediodorsal thalamus (MD), because of their potential participation in conditioned fear inhibition; combined lesions including the mPFC with the MO, SEP, or MD were also made. The lesions were made either 1 wk before conditioning or 1 d after extinction training. All rats normally extinguished their conditioned freezing behavior during extinction training and did not display any return of this behavior during the retention test. These data reveal that the mPFC is not required for the acquisition, the expression, or the retrieval of extinction memories but do not exclude the possibility that the mPFC normally participates in these processes.     

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.