Long-term Object Memory Research Articles

Adaptation of the Arizona Cognitive Task Battery for use with the Ts65Dn mouse model (Mus musculus) of Down syndrome.

We propose and validate a clear strategy to efficiently and comprehensively characterize neurobehavioral deficits in the Ts65Dn mouse model of Down syndrome. This novel approach uses neurocognitive theory to design and select behavioral tasks that test specific hypotheses concerning the results of Down syndrome. In this article, we model the Arizona Cognitive Task Battery, used to study human populations with Down syndrome, in Ts65Dn mice. We observed specific deficits for spatial memory, impaired long-term memory for visual objects, acquisition and reversal of motor responses, reduced motor dexterity, and impaired adaptive function as measured by nesting and anxiety tasks. The Ts65Dn mice showed intact temporal ordering, novelty detection, and visual object recognition with short delays. These results phenocopy the performance of participants with Down syndrome on the Arizona Cognitive Task Battery. This approach extends the utility of mouse models of Down syndrome by integrating the expertise of clinical neurology and cognitive neuroscience into the mouse behavioral laboratory. Further, by directly emphasizing the reciprocal translation of research between human disease states and the associated mouse models, we demonstrate that it is possible for both groups to mutually inform each other's research to more efficiently generate hypotheses and elucidate treatment strategies. (PsycINFO Database Record

Mood-dependent retrieval in visual long-term memory: dissociable effects on retrieval probability and mnemonic precision

ABSTRACTAlthough memories are more retrievable if observers’ emotional states are consistent between encoding and retrieval, it is unclear whether the consistency of emotional states increases the likelihood of successful memory retrieval, the precision of retrieved memories, or both. The present study tested visual long-term memory for everyday objects while consistent or inconsistent emotional contexts between encoding and retrieval were induced using background grey-scale images from the International Affective Picture System (IAPS). In the study phase, participants remembered colours of sequentially presented objects in a negative (Experiment 1a) or positive (Experiment 2a) context. In the test phase, participants estimated the colours of previously studied objects in either negative versus neutral (Experiment 1a) or positive versus neutral (Experiment 2a) contexts. Note, IAPS images in the test phase were always visually different from those initially paired with the studied objects. We found that reinstating negative context and positive context at retrieval resulted in better mnemonic precision and a higher probability of successful retrieval, respectively. Critically, these effects could not be attributed to a negative or positive context at retrieval alone (Experiments 1b and 2b). Together, these findings demonstrated dissociable effects of emotion on the quantitative and qualitative aspects of visual long-term memory retrieval.

Resistance exercise reduces memory impairment induced by monosodium glutamate in male and female rats.

What is the central question of this study? Monosodium glutamate causes cognitive impairment. Does resistance exercise improve the performance of rats treated with monosodium glutamate? What is the main finding and its importance? Resistance exercise is effective against monosodium glutamate-induced memory impairment in male and female rats. Monosodium glutamate (MSG), a flavour enhancer in diets, causes cognitive impairment in rodents. Exercise has been reported to protect against impairment of memory in humans. In this study, we investigated whether resistance exercise improves the performance of male and female rats treated with MSG in tests of memory and motor co-ordination. Wistar rats received MSG [4g(kg body weight)-1 day-1 , s.c.] from postnatal day 1 to 10. At postnatal day 60, the animals started a resistance exercise protocol in an 80deg inclined vertical ladder apparatus and performed it during 7weeks. Rats performed object recognition and location memory tests. Resistance exercise reduced impairment in motor co-ordination of male and female rats treated with MSG. Resistance exercise was effective against the decrease in exploratory preference in the long-term recognition memory for novel objects of male rats treated with MSG. In MSG-treated female rats, resistance exercise was effective against the decrease in exploratory preference in the novel object location test. The exploratory preference of female rats in the long-term recognition memory test was similar in all groups. The short-term memory was not altered by MSG or resistance exercise in male and female rats. This study demonstrates that MSG affected the memory of male and female rats in different ways. Resistance exercise was effective against the decrease in recognition for male rats and in location memory for female rats treated with MSG. This report demonstrates the beneficial effects of resistance exercise against the prejudice of motor condition and impairment of memory induced by MSG in male and female rats.

Memory for objects and startle responsivity in the immediate aftermath of exposure to the Trier Social Stress Test

Previously, we observed enhanced long-term memory for objects used (central objects) by committee members in the Trier Social Stress Test (TSST) on the next day. In addition, startle responsivity was increased. However, response specificity to an odour involved in the stressful episode was lacking and recognition memory for the odour was poor. In the current experiments, immediate effects of the stressor on memory and startle responsivity were investigated. We hypothesised memory for central objects of the stressful episode and startle response specificity to an odour ambient during the TSST to be enhanced shortly after it, in contrast to the control condition (friendly TSST). Further, memory for this odour was also assumed to be increased in the stress group. We tested 70 male (35) and female participants using the TSST involving objects and an ambient odour. After stress induction, a startle paradigm including olfactory and visual stimuli was conducted. Indeed, memory for central objects was significantly enhanced in immediate aftermath of the stressor. Startle responsivity increased at a trend level, particularly with regard to the odour involved in the stressful episode. Moreover, the stress group descriptively tended towards a better recognition of the odour involved. The study shows that stress enhances memory for central aspects of a stressful situation before consolidation processes come into play. In addition, results preliminarily suggest that the impact of stress on startle responsivity increases in strength but decreases in specificity during the first 24h after stress exposure.

Short-term treatment with flumazenil restores long-term object memory in a mouse model of Down syndrome

Down syndrome (DS) is a common genetic cause of intellectual disability yet no pro-cognitive drug therapies are approved for human use. Mechanistic studies in a mouse model of DS (Ts65Dn mice) demonstrate that impaired cognitive function is due to excessive neuronal inhibitory tone. These deficits are normalized by chronic, short-term low doses of GABAA receptor (GABAAR) antagonists in adult animals, but none of the compounds investigated are approved for human use. We explored the therapeutic potential of flumazenil (FLUM), a GABAAR antagonist working at the benzodiazepine binding site that has FDA approval. Long-term memory was assessed by the Novel Object Recognition (NOR) testing in Ts65Dn mice after acute or short-term chronic treatment with FLUM. Short-term, low, chronic dose regimens of FLUM elicit long-lasting (>1week) normalization of cognitive function in both young and aged mice. FLUM at low dosages produces long lasting cognitive improvements and has the potential of fulfilling an unmet therapeutic need in DS.

Reconciling change blindness with long-term memory for objects.

How can we reconcile remarkably precise long-term memory for thousands of images with failures to detect changes to similar images? We explored whether people can use detailed, long-term memory to improve change detection performance. Subjects studied a set of images of objects and then performed recognition and change detection tasks with those images. Recognition memory performance exceeded change detection performance, even when a single familiar object in the postchange display consistently indicated the change location. In fact, participants were no better when a familiar object predicted the change location than when the displays consisted of unfamiliar objects. When given an explicit strategy to search for a familiar object as a way to improve performance on the change detection task, they performed no better than in a 6-alternative recognition memory task. Subjects only benefited from the presence of familiar objects in the change detection task when they had more time to view the prechange array before it switched. Once the cost to using the change detection information decreased, subjects made use of it in conjunction with memory to boost performance on the familiar-item change detection task. This suggests that even useful information will go unused if it is sufficiently difficult to extract.

SCOP/PHLPP1β mediates circadian regulation of long-term recognition memory.

Learning and memory depend on the time of day in various organisms, but it is not clear whether and how the circadian clock regulates memory performance. Here we show that consolidation of long-term recognition memory is a circadian-regulated process, which is blunted by disruption of the hippocampal clock. We focused on SCOP, a key molecule regulating hippocampus-dependent long-term memory for objects. The amounts of SCOP and its binding partner K-Ras in the hippocampal membrane rafts exhibit robust circadian changes, and SCOP knockdown in the hippocampal CA1 impairs long-term memory at night. Circadian changes in stimulus-dependent activation of ERK in the hippocampal neurons are dependent on the SCOP levels in the membrane rafts, while Scop knockout abrogates the activation rhythm. We conclude that long-term memory formation is regulated by the circadian clock through SCOP dynamics in the membrane rafts of the hippocampal CA1.

Temporary inactivation reveals that the CA1 region of the mouse dorsal hippocampus plays an equivalent role in the retrieval of long-term object memory and spatial memory

Recognition of a previously experienced item or object depends upon the successful retrieval of memory for the object. The neural mechanisms that support object recognition memory in the mammalian brain are not well understood. The rodent hippocampus plays a well-established role in spatial memory, and we previously demonstrated that temporary inactivation of the mouse hippocampus impairs object memory, as assessed with a novel object preference (NOP) test. The present studies were designed to test some remaining issues regarding the contribution of the CA1 sub-region of the mouse dorsal hippocampus to long-term object memory. Specifically, we examined whether the retrieval of spatial memory (as assessed by the Morris water maze; MWM) and object recognition memory are differentially sensitive to inactivation of the CA1 region. The current study used pre-test local microinfusion of muscimol directly into the CA1 region of dorsal hippocampus to temporarily interrupt its function during the respective retrieval phases of both behavioral tasks, in order to compare the contribution of the CA1 to object memory and spatial memory. Histological analyses revealed that local intra-CA1 injection of muscimol diffused within, and not beyond, the CA1 region of dorsal hippocampus. The degree of memory retrieval impairment induced by muscimol was comparable in the two tasks, supporting the view that object memory and spatial memory depend similarly on the CA1 region of rodent hippocampus. Further, we confirmed that the muscimol-induced impairment of CA1 function is temporary. First, mice that exhibited impaired object memory retrieval immediately after intra-CA1 muscimol, subsequently exhibited unimpaired retrieval of object memory when tested 24h later. Secondly, a cohort of mice that exhibited impaired object memory retrieval after intra-CA1 muscimol later acquired spatial memory in the MWM comparable to that of control mice. Together, these results offer further support for the involvement of the CA1 region of mouse hippocampus in object recognition memory, and provide evidence to suggest that the NOP task is as much a test of hippocampal function as the classic MWM test.

Bias effects of short- and long-term color memory for unique objects.

Are objects remembered with a more saturated color? Some of the evidence supporting this statement comes from research using "memory colors"-the typical colors of particular objects, for example, the green of grass. The problematic aspect of these findings is that many different exemplars exist, some of which might exhibit a higher saturation than the one measured by the experimenter. Here we avoid this problem by using unique personal items and comparing long- and short-term color memory matches (in hue, value, and chroma) with those obtained with the object present. Our results, on average, confirm that objects are remembered as more saturated than they are.

Forgetting of long-term memory requires activation of NMDA receptors, L-type voltage-dependent Ca2+ channels, and calcineurin.

In the past decades, the cellular and molecular mechanisms underlying memory consolidation, reconsolidation, and extinction have been well characterized. However, the neurobiological underpinnings of forgetting processes remain to be elucidated. Here we used behavioral, pharmacological and electrophysiological approaches to explore mechanisms controlling forgetting. We found that post-acquisition chronic inhibition of the N-methyl-D-aspartate receptor (NMDAR), L-type voltage-dependent Ca2+ channel (LVDCC), and protein phosphatase calcineurin (CaN), maintains long-term object location memory that otherwise would have been forgotten. We further show that NMDAR activation is necessary to induce forgetting of object recognition memory. Studying the role of NMDAR activation in the decay of the early phase of long-term potentiation (E-LTP) in the hippocampus, we found that ifenprodil infused 30 min after LTP induction in vivo blocks the decay of CA1-evoked postsynaptic plasticity, suggesting that GluN2B-containing NMDARs activation are critical to promote LTP decay. Taken together, these findings indicate that a well-regulated forgetting process, initiated by Ca2+ influx through LVDCCs and GluN2B-NMDARs followed by CaN activation, controls the maintenance of hippocampal LTP and long-term memories over time.

Tc1 mouse model of trisomy-21 dissociates properties of short- and long-term recognition memory

The present study examined memory function in Tc1 mice, a transchromosomic model of Down syndrome (DS). Tc1 mice demonstrated an unusual delay-dependent deficit in recognition memory. More specifically, Tc1 mice showed intact immediate (30sec), impaired short-term (10-min) and intact long-term (24-h) memory for objects. A similar pattern was observed for olfactory stimuli, confirming the generality of the pattern across sensory modalities. The specificity of the behavioural deficits in Tc1 mice was confirmed using APP overexpressing mice that showed the opposite pattern of object memory deficits. In contrast to object memory, Tc1 mice showed no deficit in either immediate or long-term memory for object-in-place information. Similarly, Tc1 mice showed no deficit in short-term memory for object-location information. The latter result indicates that Tc1 mice were able to detect and react to spatial novelty at the same delay interval that was sensitive to an object novelty recognition impairment. These results demonstrate (1) that novelty detection per se and (2) the encoding of visuo-spatial information was not disrupted in adult Tc1 mice. The authors conclude that the task specific nature of the short-term recognition memory deficit suggests that the trisomy of genes on human chromosome 21 in Tc1 mice impacts on (perirhinal) cortical systems supporting short-term object and olfactory recognition memory.

The effects of prolonged administration of norepinephrine reuptake inhibitors on long-term potentiation in dentate gyrus, and on tests of spatial and object recognition memory in rats

Phasic norepinephrine (NE) release events are involved in arousal, novelty detection and in plasticity processes underlying learning and memory in mammalian systems. Although the effects of phasic NE release events on plasticity and memory are prevalently documented, it is less understood what effects chronic NE reuptake inhibition and sustained increases in noradrenergic tone, might have on plasticity and cognitive processes in rodent models of learning and memory. This study investigates the effects of chronic NE reuptake inhibition on hippocampal plasticity and memory in rats. Rats were administered NE reuptake inhibitors (NRIs) desipramine (DMI; 0, 3, or 7.5mg/kg/day) or nortriptyline (NTP; 0, 10 or 20mg/kg/day) in drinking water. Long-term potentiation (LTP; 200Hz) of the perforant path-dentate gyrus evoked potential was examined in urethane anesthetized rats after 30–32days of DMI treatment. Short- (4-h) and long-term (24-h) spatial memory was tested in separate rats administered 0 or 7.5mg/kg/day DMI (25–30days) using a two-trial spatial memory test. Additionally, the effects of chronically administered DMI and NTP were tested in rats using a two-trial, Object Recognition Test (ORT) at 2- and 24-h after 45 and 60days of drug administration. Rats administered 3 or 7.5mg/kg/day DMI had attenuated LTP of the EPSP slope but not the population spike at the perforant path-dentate gyrus synapse. Short- and long-term memory for objects is differentially disrupted in rats after prolonged administration of DMI and NTP. Rats that were administered 7.5mg/kg/day DMI showed decreased memory for a two-trial spatial task when tested at 4-h. In the novel ORT, rats receiving 0 or 7.5mg/kg/day DMI showed a preference for the arm containing a Novel object when tested at both 2- and 24-h demonstrating both short- and long-term memory retention of the Familiar object. Rats that received either dose of NTP or 3mg/kg/day DMI showed impaired memory at 2-h, however this impairment was largely reversed at 24-h. Animals in the high-dose NTP (20mg/kg/day) group were impaired at both short- and long-term intervals. Activity levels, used as an index of location memory during the ORT, demonstrated that rats receiving DMI were again impaired at retaining memory for location. DMI dose-dependently disrupts LTP in the dentate gyrus of anesthetized rats and also disrupts memory for tests of spatial memory when administered for long periods.

Semantic congruency but not temporal synchrony enhances long-term memory performance for audio-visual scenes.

Human long-term memory for visual objects and scenes is tremendous. Here, we test how auditory information contributes to long-term memory performance for realistic scenes. In a total of six experiments, we manipulated the presentation modality (auditory, visual, audio-visual) as well as semantic congruency and temporal synchrony between auditory and visual information of brief filmic clips. Our results show that audio-visual clips generally elicit more accurate memory performance than unimodal clips. This advantage even increases with congruent visual and auditory information. However, violations of audio-visual synchrony hardly have any influence on memory performance. Memory performance remained intact even with a sequential presentation of auditory and visual information, but finally declined when the matching tracks of one scene were presented separately with intervening tracks during learning. With respect to memory performance, our results therefore show that audio-visual integration is sensitive to semantic congruency but remarkably robust against asymmetries between different modalities.

Binding neutral information to emotional contexts: Brain dynamics of long-term recognition memory.

There is abundant evidence in memory research that emotional stimuli are better remembered than neutral stimuli. However, effects of an emotionally charged context on memory for associated neutral elements is also important, particularly in trauma and stress-related disorders, where strong memories are often activated by neutral cues due to their emotional associations. In the present study, we used event-related potentials (ERPs) to investigate long-term recognition memory (1-week delay) for neutral objects that had been paired with emotionally arousing or neutral scenes during encoding. Context effects were clearly evident in the ERPs: An early frontal ERP old/new difference (300-500 ms) was enhanced for objects encoded in unpleasant compared to pleasant and neutral contexts; and a late central-parietal old/new difference (400-700 ms) was observed for objects paired with both pleasant and unpleasant contexts but not for items paired with neutral backgrounds. Interestingly, objects encoded in emotional contexts (and novel objects) also prompted an enhanced frontal early (180-220 ms) positivity compared to objects paired with neutral scenes indicating early perceptual significance. The present data suggest that emotional--particularly unpleasant--backgrounds strengthen memory for items encountered within these contexts and engage automatic and explicit recognition processes. These results could help in understanding binding mechanisms involved in the activation of trauma-related memories by neutral cues.

Visual Metamemory: Metacognitive Control and Monitoring of Long-Term Visual Memory for Objects and People

Visual Metamemory: Metacognitive Control and Monitoring of Long-Term Visual Memory for Objects and People

Visual memory for objects following foveal vision loss.

Allocation of visual attention is crucial for encoding items into visual long-term memory. In free vision, attention is closely linked to the center of gaze, raising the question whether foveal vision loss entails suboptimal deployment of attention and subsequent impairment of object encoding. To investigate this question, we examined visual long-term memory for objects in patients suffering from foveal vision loss due to age-related macular degeneration. We measured patients' change detection sensitivity after a period of free scene exploration monocularly with their worse eye when possible, and under binocular vision, comparing sensitivity and eye movements to matched normal-sighted controls. A highly salient cue was used to capture attention to a nontarget location before a target change occurred in half of the trials, ensuring that change detection relied on memory. Patients' monocular and binocular sensitivity to object change was comparable to controls, even after more than 4 intervening fixations, and not significantly correlated with visual impairment. We conclude that extrafoveal vision suffices for efficient encoding into visual long-term memory.

Mind the gap: Delayed manifestation of long-term object memory improvement by phosphodiesterase inhibitors

We examined the temporal profile of pharmacologically enhanced episodic memory, using the object recognition task. Male Wistar rats were tested at different retention intervals ranging from 1h to 24h. The object discrimination performance of all groups (untreated, placebo, drug treatment) gradually decreased up to an interval (8h). Interestingly, only after this 8h interval the memory improving effects of vardenafil and rolipram started to emerge. This time-dependent memory performance shows similarities with the Kamin effect. The delayed manifestation of drug-enhanced memory suggests that two separate memory mechanisms are at play, a quick transient form of memory and a more stable memory form that requires several hours to develop. It is important to take this into account when testing treatments intended for long-term memory enhancement.

Olfactory ability and object memory in three mouse models of varying body weight, metabolic hormones, and adiposity

Physiological and nutritional state can modify sensory ability and perception through hormone signaling. Obesity and related metabolic disorders present a chronic imbalance in hormonal signaling that could impact sensory systems. In the olfactory system, external chemical cues are transduced into electrical signals to encode information. It is becoming evident that this system can also detect internal chemical cues in the form of molecules of energy homeostasis and endocrine hormones, whereby neurons of the olfactory system are modulated to change animal behavior towards olfactory cues. We hypothesized that chronic imbalance in hormonal signaling and energy homeostasis due to obesity would thereby disrupt olfactory behaviors in mice. To test this idea, we utilized three mouse models of varying body weight, metabolic hormones, and visceral adiposity — 1) C57BL6/J mice maintained on a condensed-milk based, moderately high-fat diet (MHF) of 32% fat for 6months as the diet-induced obesity model, 2) an obesity-resistant, lean line of mice due to a gene-targeted deletion of a voltage-dependent potassium channel (Kv1.3-null), and 3) a genetic model of obesity as a result of a gene-targeted deletion of the melanocortin 4 receptor (MC4R-null). Diet-induced obese (DIO) mice failed to find a fatty-scented hidden peanut butter cracker, based solely on olfactory cues, any faster than an unscented hidden marble, initially suggesting general anosmia. However, when these DIO mice were challenged to find a sweet-scented hidden chocolate candy, they had no difficulty. Furthermore, DIO mice were able to discriminate between fatty acids that differ by a single double bond and are components of the MHF diet (linoleic and oleic acid) in a habituation–dishabituation paradigm. Obesity-resistant, Kv1.3-null mice exhibited no change in scented object retrieval when placed on the MHF-diet, nor did they perform differently than wild-type mice in parallel habituation–dishabituation paradigms of fatty food-related odor components. Genetically obese, MC4R-null mice successfully found hidden scented objects, but did so more slowly than lean, wild-type mice, in an object-dependent fashion. In habituation–dishabituation trials of general odorants, MC4R-null mice failed to discriminate a novel odor, but were able to distinguish two fatty acids. Object memory recognition tests for short- and long-term memory retention demonstrated that maintenance on the MHF diet did not modify the ability to perform these tasks independent of whether mice became obese or were resistant to weight gain (Kv1.3-null), however, the genetically predisposed obese mice (MC4R-null) failed the long-term object memory recognition performed at 24h. These results demonstrate that even though both the DIO mice and genetically predisposed obese mice are obese, they vary in the degree to which they exhibit behavioral deficits in odor detection, odor discrimination, and long-term memory.

Interfering with Fos expression in rat perirhinal cortex impairs recognition memory.

Previous work has shown that immunohistochemical imaging of Fos protein is a reliable marker for changes in activity related to recognition memory in the perirhinal (PRH) cortex of the medial temporal lobe; however, whether PRH Fos expression is necessary for recognition memory had not been established. To investigate this potential requirement, antisense Fos oligodeoxynucleotide (ODN) was infused locally into PRH cortex to interfere with Fos production. As in previous studies, differential Fos expression produced by viewing novel or familiar visual stimuli was measured by immunohistochemistry: antisense Fos ODN infusion into PRH cortex disrupted the normal pattern of differential Fos expression in PRH cortex. The effect of antisense Fos ODN infusion into PRH cortex was therefore sought on recognition memory. Infusion before or immediately after acquisition impaired recognition memory for objects when the memory delay was 3 or 24 h, but not when the delay was 20 min, or when the ODN was infused before retrieval after a 24-h delay. The findings indicate a role for Fos in consolidation processes underlying long-term recognition memory for objects and establish that interfering with its expression impairs recognition memory. Antisense Fos ODN infusion also impaired object-in-place recognition memory. The results demonstrate that Fos is necessary for neuronal mechanisms in PRH cortex essential to recognition memory.

Neural Correlates of Long-Term Object Memory in the Mouse Anterior Cingulate Cortex

Damage to the hippocampal formation results in a profound temporally graded retrograde amnesia, implying that it is necessary for memory acquisition but not its long-term storage. It is therefore thought that memories are transferred from the hippocampus to the cortex for long-term storage in a process called systems consolidation (Dudai and Morris, 2000). Where in the cortex this occurs remains an open question. Recent work (Frankland et al., 2005; Vetere et al., 2011) suggests the anterior cingulate cortex (ACC) as a likely candidate area, but there is little direct electrophysiological evidence to support this claim. Previously, we demonstrated object-associated firing correlates in caudal ACC during tests of recognition memory and described evidence of neuronal responses to where an object had been following a brief delay. However, long-term memory requires evidence of more durable representations. Here we examined the activity of ACC neurons while testing for long-term memory of an absent object. Mice explored two objects in an arena and then were returned 6 h later with one of the objects removed. Mice continued to explore where the object had been, demonstrating memory for that object. Remarkably, some ACC neurons continued to respond where the object had been, while others developed new responses in the absent object's location. The incidence of absent-object responses by ACC neurons was greatly increased with increased familiarization to the objects, and such responses were still evident 1 month later. These data strongly suggest that the ACC contains neural correlates of consolidated object/place association memory.