Long-term Object Memory Research Articles

Impact of prenatal ischemia on behavior, cognitive abilities and neuroanatomy in adult rats with white matter damage

Early brain damage, such as white matter damage (WMD), resulting from perinatal hypoxia–ischemia in preterm and low birth weight infants represents a high risk factor for mortality and chronic disabilities, including sensory, motor, behavioral and cognitive disorders. In previous studies, we developed a model of WMD based on prenatal ischemia (PI), induced by unilateral ligation of uterine artery at E17 in pregnant rats. We have shown that PI reproduced some of the main deficits observed in preterm infants, such as white and gray matter damage, myelination deficits, locomotor, sensorimotor, and short-term memory impairments, as well as related musculoskeletal and neuroanatomical histopathologies [1–3]. Here, we determined the deleterious impact of PI on several behavioral and cognitive abilities in adult rats, as well as on the neuroanatomical substratum in various related brain areas. Adult PI rats exhibited spontaneous exploratory and motor hyperactivity, deficits in information encoding, and deficits in short- and long-term object memory tasks, but no impairments in spatial learning or working memory in watermaze tasks. These results were in accordance with white matter injury and damage in the medial and lateral entorhinal cortices, as detected by axonal degeneration, astrogliosis and neuronal density. Although there was astrogliosis and axonal degeneration in the fornix, hippocampus and cingulate cortex, neuronal density in the hippocampus and cingulate cortex was not affected by PI. Levels of spontaneous hyperactivity, deficits in object memory tasks, neuronal density in the medial and lateral entorhinal cortices, and astrogliosis in the fornix correlated with birth weight in PI rats. Thus, this rodent model of WMD based on PI appears to recapitulate the main neurobehavioral and neuroanatomical human deficits often observed in preterm children with a perinatal history of ischemia.

Long-term object location memory in rats: Effects of sample phase and delay length in spontaneous place recognition test

This study investigates the effects of sample phase and delay length on discrimination performance in the spontaneous place recognition (SPR) test in rats. Rats were allowed to explore an arena where two identical objects were presented for 5–20min (sample phase). After a delay interval, rats were placed again in the same arena but one of the two objects was moved to a novel place (test phase). Results showed that when the sample phase was as long as 20min, rats preferentially explored the moved object during the test phase even after a 6–24h delay was interposed. Further sequential and cumulative analyses of the test phase revealed that the preference for the object in a novel place was evident in the first and 2ndmin of the test phase in rats with a longer sample phase duration. Correlation analysis showed that locomotor activity and object exploration in the sample phase were not decisive factors in spatial memory performance. The present results demonstrate the importance of the sample phase exposure time and the test phase length.

Evaluation of object-based attention in mice

The deficits of attention result in significant impairment in daily life, and pharmacological intervention to improve attention is the most effective treatment in clinics. However, methods which are suitable for the large scale preclinical screening of attention-improving compounds or drugs are few in the field. In this study, we have developed object-based attention task as a simple and wherever-practical method that suitable for quick drug screening in mice. Treatment with p-chlorophenylalanine (pCPA) (200 mg/kg/day, i.p.) for three consecutive days reduced the prefrontal cortical content of serotonin and dopamine, and increased turn-over of dopamine while decreasing turn-over of norepinephrine in the prefrontal cortex on day 7. Auditory attention and working memory, but not long-term object memory after a long (10 min) object (two objects)-exposure period, were impaired on day 7 after the same treatment paradigm with pCPA. Novel object recognition ability immediately (<10 s) after a short (3 min) object (on two objects)-exposure period was not impaired after pCPA treatment. However, novel object recognition ability immediately (<10 s) after a short (3 min), but not long (6 min), object (five objects)-exposure period was impaired after pCPA treatment. For the verification, the current task, the object-based attention task, was confirmed in an attention deficit model induced by acute phencyclidine (1 mg/kg, i.p.) treatment in mice. It was implied that the object-based attention task would assist the behavioral screening process of pharmacological studies on attention-improving drugs.

Deficits in long-term recognition memory reveal dissociated subtypes in congenital prosopagnosia.

The study investigates long-term recognition memory in congenital prosopagnosia (CP), a lifelong impairment in face identification that is present from birth. Previous investigations of processing deficits in CP have mostly relied on short-term recognition tests to estimate the scope and severity of individual deficits. We firstly report on a controlled test of long-term (one year) recognition memory for faces and objects conducted with a large group of participants with CP. Long-term recognition memory is significantly impaired in eight CP participants (CPs). In all but one case, this deficit was selective to faces and didn't extend to intra-class recognition of object stimuli. In a test of famous face recognition, long-term recognition deficits were less pronounced, even after accounting for differences in media consumption between controls and CPs. Secondly, we combined test results on long-term and short-term recognition of faces and objects, and found a large heterogeneity in severity and scope of individual deficits. Analysis of the observed heterogeneity revealed a dissociation of CP into subtypes with a homogeneous phenotypical profile. Thirdly, we found that among CPs self-assessment of real-life difficulties, based on a standardized questionnaire, and experimentally assessed face recognition deficits are strongly correlated. Our results demonstrate that controlled tests of long-term recognition memory are needed to fully assess face recognition deficits in CP. Based on controlled and comprehensive experimental testing, CP can be dissociated into subtypes with a homogeneous phenotypical profile. The CP subtypes identified align with those found in prosopagnosia caused by cortical lesions; they can be interpreted with respect to a hierarchical neural system for face perception.

Redundancy effects in the perception and memory of visual objects

Is visual representation of an object affected by whether surrounding objects are identical to it, different from it, or absent? To address this question, we tested perceptual priming, visual short-term, and long-term memory for objects presented in isolation or with other objects. Experiment 1 used a priming procedure, where the prime display contained a single face, four identical faces, or four different faces. Subjects identified the gender of a subsequent probe face that either matched or mismatched with one of the prime faces. Priming was stronger when the prime was four identical faces than when it was a single face or four different faces. Experiments 2 and 3 asked subjects to encode four different objects presented on four displays. Holding memory load constant, visual memory was better when each of the four displays contained four duplicates of a single object, than when each display contained a single object. These results suggest that an object's perceptual and memory representations are enhanced when presented with identical objects, revealing redundancy effects in visual processing.

Conceptual distinctiveness supports detailed visual long-term memory for real-world objects.

Humans have a massive capacity to store detailed information in visual long-term memory. The present studies explored the fidelity of these visual long-term memory representations and examined how conceptual and perceptual features of object categories support this capacity. Observers viewed 2,800 object images with a different number of exemplars presented from each category. At test, observers indicated which of 2 exemplars they had previously studied. Memory performance was high and remained quite high (82% accuracy) with 16 exemplars from a category in memory, demonstrating a large memory capacity for object exemplars. However, memory performance decreased as more exemplars were held in memory, implying systematic categorical interference. Object categories with conceptually distinctive exemplars showed less interference in memory as the number of exemplars increased. Interference in memory was not predicted by the perceptual distinctiveness of exemplars from an object category, though these perceptual measures predicted visual search rates for an object target among exemplars. These data provide evidence that observers' capacity to remember visual information in long-term memory depends more on conceptual structure than perceptual distinctiveness.

Normative Data for the Pyramids and Palm Trees Test in the Quebec-French Population

Semantic memory tests assess long-term memory for facts, objects, and concepts as well as words and their meaning. Since it holds culturally shared information, the development of normative data adjusted to the cultural and linguistic reality of the target population is of particular importance. The present study aimed to establish normative data for the Pyramids and Palm Trees Test, a commonly used test of semantic memory, in the French-Quebec population. The normative sample consisted of 214 healthy French-speaking adults and elderly persons from various regions of the province of Quebec. The effects of participants' age, gender, and education level on test performance were assessed. Results indicated that participants' level of education and age, but not sex, were found to be significantly associated with performance on this test. Normative data are presented as means and standard deviations. Overall, the present norms are consistent with those of previous studies with Spanish samples.

Protein Phosphatase 1 Regulates the Histone Code for Long-Term Memory

Chromatin remodeling through histone posttranslational modifications (PTMs) and DNA methylation has recently been implicated in cognitive functions, but the mechanisms involved in such epigenetic regulation remain poorly understood. Here, we show that protein phosphatase 1 (PP1) is a critical regulator of chromatin remodeling in the mammalian brain that controls histone PTMs and gene transcription associated with long-term memory. Our data show that PP1 is present at the chromatin in brain cells and interacts with enzymes of the epigenetic machinery including HDAC1 (histone deacetylase 1) and histone demethylase JMJD2A (jumonji domain-containing protein 2A). The selective inhibition of the nuclear pool of PP1 in forebrain neurons in transgenic mice is shown to induce several histone PTMs that include not only phosphorylation but also acetylation and methylation. These PTMs are residue-specific and occur at the promoter of genes important for memory formation like CREB (cAMP response element-binding protein) and NF-kappaB (nuclear factor-kappaB). These histone PTMs further co-occur with selective binding of RNA polymerase II and altered gene transcription, and are associated with improved long-term memory for objects and space. Together, these findings reveal a novel mechanism for the epigenetic control of gene transcription and long-term memory in the adult brain that depends on PP1.

Awake Intranasal Insulin Delivery Modifies Protein Complexes and Alters Memory, Anxiety, and Olfactory Behaviors

The role of insulin pathways in olfaction is of significant interest with the widespread pathology of diabetes mellitus and its associated metabolic and neuronal comorbidities. The insulin receptor (IR) kinase is expressed at high levels in the olfactory bulb, in which it suppresses a dominant Shaker ion channel (Kv1.3) via tyrosine phosphorylation of critical N- and C-terminal residues. We optimized a 7 d intranasal insulin delivery (IND) in awake mice to ascertain the biochemical and behavioral effects of insulin to this brain region, given that nasal sprays for insulin have been marketed notwithstanding our knowledge of the role of Kv1.3 in olfaction, metabolism, and axon targeting. IND evoked robust phosphorylation of Kv1.3, as well as increased channel protein-protein interactions with IR and postsynaptic density 95. IND-treated mice had an increased short- and long-term object memory recognition, increased anxiolytic behavior, and an increased odor discrimination using an odor habituation protocol but only moderate change in odor threshold using a two-choice paradigm. Unlike Kv1.3 gene-targeted deletion that alters metabolism, adiposity, and axonal targeting to defined olfactory glomeruli, suppression of Kv1.3 via IND had no effect on body weight nor the size and number of M72 glomeruli or the route of its sensory axon projections. There was no evidence of altered expression of sensory neurons in the epithelium. In mice made prediabetic via diet-induced obesity, IND was no longer effective in increasing long-term object memory recognition nor increasing anxiolytic behavior, suggesting state dependency or a degree of insulin resistance related to these behaviors.

Sex differences in object location memory: The female advantage of immediate detection of changes

Object location memory has been considered the only spatial ability in which females display an advantage over males. We examined sex differences in long-term object location memory. After participants studied an array of objects, they were asked to recall the locations of these objects three minutes later or one week later. Results showed a female advantage only in the three-minute memory task. Additionally, we analyzed sex differences in the ability to recognize both location-exchanged and location-maintained objects. Females were superior to males at recognizing location-exchanged objects after three minutes, but not after one week. Although the one-week group's memory performance for location-exchanged objects was marginally lower, some members of that group recognized the location-maintained objects at higher levels of performance. Therefore, we concluded that the female advantage in object location memory is limited to immediate detection of changes. The relevant evolutionary theories are discussed.

P2-459: Long-lasting improvement in long-term object memory after subchronic rolipram treatment

P2-459: Long-lasting improvement in long-term object memory after subchronic rolipram treatment

Sub-chronic rolipram treatment leads to a persistent improvement in long-term object memory in rats

In the present study the effects of sub-chronic rolipram treatment in an object recognition task in 3-month-old male rats were investigated. Rats remember which object they have explored in a previous trial (T1) when they are tested 1 h later (T2). However, when tested 24 h later, they do not remember which object was presented to them in the first trial. Drug treatments may improve discrimination performance after 24 h, i.e., improve memory for the familiar object. Rats were sub-chronically treated with 0.5 mg/kg rolipram (p.o.) for five consecutive days and tested with a 24 h delay between T1 and T2. Memory performance in the object recognition task was assessed before, during and after sub-chronic treatment. In addition, we investigated whether the timing of the final dose, i.e., 24, 1, or 6 h before training, had an effect on memory performance. During sub-chronic treatment, i.e., after 2–3 days of rolipram treatment, moderate effects on memory performance were observed. Regardless of when the final administration was given, sub-chronic rolipram treatment improved long-term memory performance. Since plasma and brain rolipram levels were undetectable at 24 h before the test, and acute treatment with rolipram 24 h before training had no effects, the observed memory enhancement cannot be attributed to acute rolipram effects. The long-term memory enhancing effects of rolipram might be explained by long-lasting neuronal changes by the chronic treatment due to recurring activation of the cAMP/PKA/CREB pathway leading to CREB phosphorylation.

A biologically motivated visual memory architecture for online learning of objects

We present a biologically motivated architecture for object recognition that is based on a hierarchical feature-detection model in combination with a memory architecture that implements short-term and long-term memory for objects. A particular focus is the functional realization of online and incremental learning for the task of appearance-based object recognition of many complex-shaped objects. We propose some modifications of learning vector quantization algorithms that are especially adapted to the task of incremental learning and capable of dealing with the stability-plasticity dilemma of such learning algorithms. Our technical implementation of the neural architecture is capable of online learning of 50 objects within less than three hours.

Proteolytic Degradation of SCOP in the Hippocampus Contributes to Activation of MAP Kinase and Memory

Because activation of ERK1/2 MAP kinase (MAPK) is critical for hippocampus-dependent memory, there is considerable interest in mechanisms for regulation of MAPK during memory formation. Here we report that MAPK and CREB-mediated transcription are negatively regulated by SCOP (suprachiasmatic nucleus [SCN] circadian oscillatory protein) and that SCOP is proteolyzed by calpain when hippocampal neurons are stimulated by brain-derived neurotrophic factor (BDNF), KCl depolarization, or NMDA. Moreover, training for novel object memory decreases SCOP in the hippocampus. To determine if hippocampus-dependent memory is influenced by SCOP in vivo, we generated a transgenic mouse strain for the inducible overexpression of SCOP in the forebrain. Overexpression of SCOP completely blocked memory for novel objects. We conclude that degradation of SCOP by calpain contributes to activation of MAPK during memory formation.

The hippocampus and long-term object memory in the rat

Animal models of amnesia have yielded many insights into the neural substrates of different types of memories. Some very important aspects of memory, however, have been ignored in research using experimental animals. For example, to examine long-term memory investigators traditionally have relied on measures of information acquisition, which stand in contrast to the measures of retention commonly used in work with humans. We have recently developed a behavioral paradigm that measures both the acquisition and long-term retention of object discriminations, and found a selective retention impairment in rats with entorhinal-hippocampal disconnection (Vnek et al., 1995). The present study was designed to determine whether direct damage to the hippocampus likewise would lead to a selective deficit in the retention of visual discriminations. Rats with aspiration lesions of the dorsal hippocampus, rats with neocortical control lesions, and normal controls were trained on three object discrimination problems and then retrained 3 weeks later to measure retention. All animals showed the same level of performance during the training (acquisition) phase of testing, but the performance of animals with dorsal hippocampal injury fell below that of controls during retraining (retention). Taken together, these and our earlier results suggest that the hippocampus and anatomically related structures are particularly important for retaining visual discriminations over long delay intervals. These findings may clarify the role of the hippocampus in nonspatial memory.

The long-term retention of events in monkey memory

Nine monkeys ( Macaca fascicularis) demonstrated long-term memory for objects in a recognition task based on the non-matching-to-sample (NMTS) paradigm. In this task, the subjects were required to choose a novel object when it was paired with an alternative that had become familiar in previous NMTS training. When the familiar objects had been experienced an average of 3.4 times 4–9 months previously, 5 monkeys made 79% correct choices of the novel object. Three other monkeys exposed to the objects a mean of 12.8 times were 65% accurate at retention intervals of 20 months. A ninth subject achieved an accuracy of 68% after a retention interval of 34 months based on an exposure frequency of 10.6. These levels of performance indicate that in monkey event memory the mnemonic representation of an object is quite durable and a proportion of visual information may last for at least 3 years.