Neuropeptide Trefoil factor 3 improves learning and retention of novel object recognition memory in mice

Accumulating evidence has implicated neuropeptides in modulating recognition, learning and memory. However, to date, no study has investigated the effects of neuropeptide Trefoil factor 3 (TFF3) on the process of learning and memory. In the present study, we evaluated the acute effects of TFF3 administration (0.1 and 0.5 mg/kg, i.p.) on the acquisition and retention of object recognition memory in mice. We found that TFF3 administration significantly enhanced both short-term and long-term memory during the retention test, conducted 90 min and 24 h after training respectively. Remarkably, acute TFF3 administration transformed a learning event that would not normally result in long-term memory into an event retained for a long-term period and produced no effect on locomotor activity in mice. In conclusion, the present results provide an important role of TFF3 in improving object recognition memory and reserving it for a longer time, which suggests a potential therapeutic application for diseases with recognition and memory impairment.     

The role of the vertical meridian in visual memory for objects

It is widely believed that, in human and nonhuman primates, visual memories of objects are stored in the temporal lobe. Electrophysiological results in monkeys, however, indicate that when a visual scene contains two or more objects, with at least one object in each visual hemifield, neurons in the temporal lobe of each hemisphere respond only to the objects that are in the contralateral visual hemifield, and their activity is unaffected by the objects in the ipsilateral hemifield. Putting these two premises together predicts that object memory should fail, or at least suffer a substantial decrement, when an object is presented for learning and retention as part of such a scene, but crosses the vertical meridian between the learning trial and the retention test. The effect of this change should be much greater than the effect of an equal retinal translation that crosses the horizontal rather than the vertical meridian. An experiment with normal human subjects verified this prediction under conventional conditions of tachistoscopic viewing, with a single constant fixation spot. A further condition in the same experiment, however, tested the same retinal translations in a more naturalistic condition, where the retinal changes were produced by varying the position on the display screen of the fixation spot rather than of the objects. Here, there was no significant special effect of crossing the vertical meridian. We conclude that visual memories are not stored exclusively in the temporal lobe.     

A new automated method to assess the rat recognition memory: validation of the method

During the last decade, the rodent object recognition memory task had gained popularity in the field of pharmacological studies, and has been proposed as a useful method to evaluate the efficacy of memory enhancing compounds. In this context, it is important to establish reliable and automated methods with high throughput to evaluate recognition memory in the rat. When performed in a Y-maze apparatus, object recognition has been described to be less dependent on spatial information, and we here report a new method to assess novelty discrimination in a Y-maze apparatus recorded via automated video tracking. During the development of the method, many parameters were recorded and some were selected as being the most reliable, i.e. time spent in the distal half-arms during the first 2 min of the test. The method was then validated under memory deficit conditions produced by a pharmacological treatment (scopolamine) and a long retention delay (72 h) between the sample and the test. The time-induced deficit was prevented by administration of a M1 positive allosteric modulator, BQCA at a dose of 10 mg/kg. Altogether, our data show that the novelty discrimination task performed in a Y-maze apparatus is a reliable method to assess the recognition memory of the rat. This new automated method is as sensitive as the classical object recognition test, and provides advantages such as easily definable parameters and the possibility to use an automated video tracking system that makes the measurement independent of the investigator.     

Short toxic methamphetamine schedule impairs object recognition task in male rats

Performance on object recognition and object placement memory tasks was evaluated after a short-dosing model of methamphetamine (MA) regime and monoamines and metabolites were measured post-testing. Adult male rats received three injections of 10 mg/kg at 2-h intervals. In striatum DA and 5-HT were depleted by 65% and 79%, respectively, no significant changes were found in pre-frontal cortex, hippocampus, ventral tegmental area (VTA) or substantia nigra. The experimental group also showed less exploratory activity in the open field and the sample trials of both object recognition and object placement tasks. MA groups also showed decreased performance in the object recognition trial (1-h and 2-h inter-trial delays). Less exploration of the objects in the sample trial by the MA group might indicate deficits in general exploratory drive and/or to initiate actions. Nevertheless, in the spatial version of the recognition test (object placement task) the experimental group performed as well as the control group in two of the three delays (2 h and 4 h) even with significantly lower total exploration times in the sample trial. Our results demonstrate that a short toxic schedule induced profound changes in neurochemistry (comparable to classic acute toxic models of MA: four injections of 10 mg/kg) but selective declines in behavioral tasks.     

Findings from animals concerning when interactions between perirhinal cortex, hippocampus and medial prefrontal cortex are necessary for recognition memory

Loss of recognition memory is a prominent feature of the human classical amnesic syndrome. Recognition memory requires judgments concerning prior occurrence. Such judgments can be made in a variety of ways using different types of information such as the relative familiarity of individual objects or locations, or the location of a previously encountered object, or when an object was previously encountered. We review findings of selective ablation studies which demonstrate that the perirhinal cortex, hippocampus and medial prefrontal cortex are differently involved in recognition memory processes involving these different types of information. This review also presents data from a series of disconnection analyses, which test whether the perirhinal cortex, hippocampus and medial prefrontal cortex form components of an integrated system for these recognition memory processes. These analyses reveal that it is necessary for the perirhinal cortex, medial prefrontal cortex and the hippocampus to interact, forming an integrated network, in recognition memory involving judgment of whether an object has been previously encountered in a particular place (object-in-place recognition memory) and in judging which of two objects was encountered longer ago (temporal order memory). In contrast, such interactions are not necessary when judgments are made concerning the prior occurrence of an individual item without positional information being necessary for the judgment (object memory) or concerning the prior occurrence of some item at a particular location without object information being necessary for the judgment (location memory).     

Common prefrontal activations during working memory,episodic memory,and semantic memory

Regions of the prefrontal cortex (PFC) are typically activated in many different cognitive functions. In most studies, the focus has been on the role of specific PFC regions in specific cognitive domains, but more recently similarities in PFC activations across cognitive domains have been stressed. Such similarities may suggest that a region mediates a common function across a variety of cognitive tasks. In this study, we compared the activation patterns associated with tests of working memory, semantic memory and episodic memory. The results converged on a general involvement of four regions across memory tests. These were located in left frontopolar cortex, left mid-ventrolateral PFC, left mid-dorsolateral PFC and dorsal anterior cingulate cortex. These findings provide evidence that some PFC regions are engaged during many different memory tests. The findings are discussed in relation to theories about the functional contribution of the PFC regions and the architecture of memory.     

Post-training progesterone dose-dependently enhances object, but not spatial, memory consolidation

The aim of this study was to determine if progesterone modulates object and spatial memory consolidation in young ovariectomized C57BL/6 mice. Object memory was tested in an object recognition task using 24- and 48-h delays. Spatial memory was tested in a 2-day version of the Morris water maze in which retention was tested 24 or 48h after training. Immediately after training in each task, mice received a single intraperitoneal injection of vehicle or 5, 10, or 20mg/kg water-soluble progesterone. Mice were then tested 24 or 48h later in the absence of circulating progesterone. Post-training injections of 10 and 20mg/kg progesterone enhanced object recognition, but not memory in the spatial water maze. These findings suggest that object memory consolidation in young female mice is more sensitive to the modulatory effects of progesterone than spatial memory consolidation, at least using the tasks, doses, and delays tested. As such, these findings may have important implications for the design of progesterone therapies intended to reduce age-related memory decline.     

Food deprivation modulates chronic stress effects on object recognition in male rats: role of monoamines and amino acids

An object recognition task was used to determine if chronic restraint stress (6 h/day for 21 days) impairs non-spatial memory, since chronic restraint is known to impair spatial memory. In addition, food deprivation was tested as a possible modulating factor of any stress effect in this non-reward-dependent task. Following 3 weeks of daily restraint, subjects were tested for open field activity and object recognition (over different delay intervals) during one week in two separate experiments. Experiment 1 involved testing under low demand conditions (small arena) while experiment 2 involved testing under higher-demand conditions (large arena). Basal monoamine and amino acid levels (home cage) were assessed in experiment one and monoamine arousal levels (following a sample trial) were assessed in experiment two. We observed that chronic stress impaired object recognition when the delay was extended beyond 1 h, and that food deprivation could attenuate the degree of impairment. In addition, chronic stress was associated with increased norepinephrine levels in both the amygdala and hippocampus, and dopamine (HVA/DA, DOPAC/DA) in prefrontal cortex. These changes were not observed in stress subjects that were subsequently food deprived. Food deprived subjects had higher basal serotonin activity in prefrontal cortex and hippocampus as well as higher serum CORT levels. Results suggest that food deprivation may act as a novel stress, thereby increasing subjects' arousal and attention toward the objects, which aids stressed subjects, especially in low-demand conditions. Both restraint and food deprivation affected select limbic areas associated with memory functioning.     

Dreams,Perception, and Creative Realization

This article draws on the ethnography of Aboriginal Australia to argue that perceptual openness, extending from waking life into dreaming experience, provides an important cognitive framework for the apprehension of dreamt experience in these contexts. I argue that this perceptual openness is analogous to the “openness to experience” described as a personality trait that had been linked with dream recall frequency (among other things). An implication of identifying perceptual openness at a cultural rather than at an individual level is two-fold. It provides an example of the ways in which cultural differences affect perception, indicative of cognitive diversity; and, given the relationship between dreams and creativity suggested anecdotally and through research, a cultural orientation toward perceptual openness is also likely to have implications for the realization of creativity that occurs through dreams. Such creativity though cannot be separated from the relational context in which such dreamt material is elaborated and understood.     

地卓西平马来酸盐对雄性大鼠自发活动和前脉冲抑制及再认记忆的影响

目的 观察急性腹腔注射N-甲基-D-天冬氨酸(NMDA)受体拮抗剂地卓西平马来酸盐(MK-801)刘大鼠自发活动、感觉运动门控和物体再认记忆的影响,探讨MK-801模拟精神分裂症不同内表现型的适宜剂量.方法 成年雄性SD大鼠共104只,按照体质量采用分层随机化方法进行分组.(1)取SD大鼠48只,分为MK-801小剂量组、MK-801中剂量组、MK-801高剂量组和对照组,每组12只,观察不同剂量MK-801 (0.1、0.2、0.4 mg/kg)对大鼠自发活动的影响;(2)取SD大鼠32只,分为MK-801小剂量组、MK-801中剂量组、MK-801高剂量组和对照组,每组8只,观察不同剂量MK-801(0.1、0.2、0.4 mg/kg)对大鼠前脉冲抑制(PPI)的影响;(3)取SD大鼠24只,分为MK-801小剂量组和对照组,每组12只,观察小剂量MK-801 (0.1 mg/kg)对大鼠物体辨别测试的影响.结果 (1)中高剂量MK-801 (0.2,0.4 mg/kg)呈剂量依赖性诱导大鼠自发活动的增加以及PPI的损害(P＜0.05或P＜0.01),小剂量(0.1 mg/kg)组在自发活动和PPI上与对照组差异无统计学意义(P＞0.05).(2)小剂量MK-801组在物体辨别测试中对新物体的偏爱指数显著低于对照组[(57.79±10.66)％比(73.34±18.52)％,P＜0.05].结论 中高剂量MK-801可引起自发活动和感觉运动门控功能异常,而小剂量在排除运动系统异常的前提下可特异性地破坏大鼠的再认记忆,提示MK-801模拟精神分裂症的不同内表现型时应根据研究目的选择适宜剂量.     

Heightened susceptibility to interference in an animal model of amnesia: Impairment in encoding, storage, retrieval - or all three?

There has recently been a resurgence in the idea that amnesia may be characterized by an increased susceptibility to interference. In the present study we tested this idea using a well-controlled and well-established animal model of amnesia: impairment in object recognition following perirhinal and postrhinal cortical (PPRh) damage. We used this paradigm to test whether memory impairment was exacerbated by the interpolation of a potentially interfering item either before (proactive interference) or after (retroactive interference) the to-be-remembered item. Rats with PPRh damage were impaired in object recognition memory, with a minimal delay, when the interfering stimulus was perceptually similar to the test stimuli. When the interfering stimulus was less perceptually similar to the test stimuli, the PPRh-lesioned rats performed similarly to Controls. Both proactive and retroactive interference were observed, and both depended on the similarity of the interfering item to the test items. These findings provide support for the idea that amnesia can indeed be characterized by increased vulnerability to interference, and we illustrate, using simulations generated by a computational model of amnesia, how the mechanism for this vulnerability to interference can be understood, not in terms of an impairment in encoding, storage or retrieval, but in terms of an impairment in encoding, storage and retrieval.     

Serotonin 5-HT6 receptor blockade reverses the age-related deficits of recognition memory and working memory in mice

Studies have shown that the blockade of 5-HT6 receptors (5-HT6R) can improve memory processes and reverse age-related spatial episodic like memory deficits. Since normal aging in the human is associated with a decline in episodic and working memory, we assessed the effect of the 5-HT6R blockade (SB-271046) on recognition memory (object recognition task) (a component of episodic like memory) in parallel to working memory (spontaneous alternation task in the T-maze) performances in young, adult, aged and senescent mice. Deficits in consolidation of non spatial recognition memory that were observed in 17- and 21-month-old mice were found to be reversed by 5-HT6R blockade. Deficits in working memory performances were only apparent as late as at 25 months of age; again, these deficits were reversed by 5-HT6R blockade. This study revealed in the mouse that, as in humans, working memory is more lately altered than recognition memory during aging and that such memory deficits could be counteracted by the use of 5-HT6R antagonists.     

帕金森病患者记忆监测与情景记忆的相关研究

目的 研究帕金森病患者( Parkinson's disease,PD)对情景记忆监测情况,并进一步探讨PD患者情景记忆障碍的可能机制.方法 建立情景记忆知晓感(feeling of knowing-episodic memory,FOK-EM)判断的试验范式,对25例PD患者和25名年龄及教育程度相匹配的健康对照(HC)者进行研究.结果 与HC组的FOK-EM的回忆率(39.67％±6.11％)、再认率(58.42％±7.50％)以及FOK判断准确率(0.61 ±0.22)比较,PD患者组FOK-EM的回忆率(19.33％±5.10％)、再认率(45.93％±7.82％)以及FOK判断准确率(-0.18±0.46)显著降低,差异均有统计学意义(t=-4.833,P＜0.01;t=-2.497,P＜0.05;t=-5.986,P＜0.01);FOK-EM的肯定判断/正确再认成绩(20.47％±10.78％)以及肯定判断/错误再认成绩(即高估,29.53％±5.62％)与HC组的肯定判断/正确再认成绩(39.47％±9.47％)以及肯定判断/错误再认成绩(即高估,13.90％±5.50％)之间差异有统计学意义(t =3.564,P＜0.05;t=2.306,P＜0.05),且Stroop效应与FOK-EM的肯定判断/错误再认成绩呈正相关(r =0.640,P＜0.01).结论 PD患者的情景记忆监测受损,表现为对自身再认能力的高估.这种记忆监测受损与执行功能的损害相关,提示此机制可能是导致PD患者情景记忆障碍的重要因素.     

Early postnatal maternal deprivation in rats induces memory deficits in adult life that can be reversed by donepezil and galantamine

Early postnatal maternal deprivation is known to cause long-lasting neurobiological effects. Here, we investigated whether some of the cognitive aspects of these deficits might be related to a disruption of the cholinergic system. Pregnant Wistar rats were individually housed and maintained on a 12:12 h light/dark cycle with food and water freely available. The mothers were separated from their pups for 3 h per day from postnatal day 1 (PND-1) to PND-10. To do that, the dams were moved to a different cage and the pups maintained in the original home cage, which was transferred to a different room kept at 32 °C. After they reached 120–150 days of age, maternal-deprived and non-deprived animals were either sacrificed for brain acetylcholinesterase measurement, or trained and tested in an object recognition task and in a social recognition task as described by Rossato et al. (2007) [Rossato, J.I., Bevilaqua, L. R.M., Myskiw, J.C., Medina, J.H., Izquierdo, I., Cammarota, M. 2007. On the role hippocampal synthesis in the consolidation and reconsolidation of object recognition memory. Learn. Mem. 14, 36–46] and Lévy et al. (2003) [Lévy, F., Melo. A.I., Galef. B.G. Jr., Madden, M., Fleming. A.S. 2003. Complete maternal deprivation affects social, but not spatial, learning in adult rats. Dev. Psychobiol. 43, 177–191], respectively. There was increased acetylcholinesterase activity in hippocampus and perirhinal cortex of the deprived animals. In addition, they showed a clear impairment in memory of the two recognition tasks measured 24 h after training. Oral administration of the acetylcholinesterase inhibitors, donepezil or galantamine (1 mg/kg) 30 min before training reversed the memory impairments caused by maternal deprivation. The findings suggest that maternal deprivation affects memory processing at adulthood through a change in brain cholinergic systems.     

Amnesiacs might get the gist: Reduced false recognition in amnesia may be the result of impaired item-specific memory

It is a common finding in tests of false recognition that amnesic patients recognize fewer related lures than healthy controls, and this has led to assumptions that gist memory is damaged in these patients (Schacter, Verfaellie, & Anes, 1997, Neuropsychology, 11; Schacter, Verfaellie, Anes, & Racine, 1998, Journal of Cognitive Neuroscience, 10; Schacter, Verfaellie, & Pradere, 1996, Journal of Memory and Language, 35). However, clinical observations find that amnesic patients typically hold meaningful conversations and make relevant remarks, and there is some experimental evidence highlighting preserved immediate recall of prose (Baddeley & Wilson, 2002, Neuropsychologia, 40; Gooding, Isaac, & Mayes, 2005, Neuropsychologia, 43; Rosenbaum, Gilboa, Levine, Winocur, & Moscovitch, 2009, Neuropsychologia, 47), which suggests that amnesiacs can get the gist. The present experiment used false recognition paradigms to assess whether the reduced rate of false recognition found in amnesic patients may be a consequence of their impaired item-specific memory. It examined the effect of increasing the item-specific memory of amnesic patient DA by bringing her to criterion on relevant study-lists and compared her performance on a false recognition paradigm with a group of 32 healthy young adults. Results indicated that when DA’s item-specific memory was increased she was more able to gist and her performance was no different to the healthy young adults. Previous assumptions that gist memory is necessarily damaged in amnesia might therefore be revisited, since the reduced rate of false recognition could be caused by impaired item-specific memory. The experiment also highlights a positive relationship between item-specific and gist memory which has not previously been accounted for in false-recognition experiments.     

Spared place and object-place learning but limited spatial working memory capacity in rats with selective lesions of the dentate gyrus

We studied the cognitive performance of rats with colchicine-induced lesions of the hippocampal dentate gyrus (DG) on a range of spatial, non-spatial and mixed spatial/procedural tasks. Rats were assigned to three experimental groups receiving large colchicine lesions (7 microg per hippocampus), small colchicine lesions (1.75 microg per hippocampus) or sham lesions. Stereological estimates of cell density indicated that the colchicine treatments induced dose-dependent damage to the DG, while sparing in large part other hippocampal subfields. Remarkably, the behavioural results showed that the colchicine lesions did not affect the performance of rats in an object discrimination task, in an object-place associative task in which a familiar object was displaced from a given position nor in a spontaneous spatial discrimination task performed in the T-maze. However, rats in both lesion groups were severely impaired in a reinforced non-matching-to-position working memory task conducted in the T-maze. Importantly, performance in the working memory task correlated strongly with cell density in the DG but not with cell density in the CA1 and CA3 areas. Only rats with large-lesions showed a transient deficit in a reinforced rule-based conditional discrimination task. These data demonstrated that rats with selective lesions of the DG readily acquire and retain neural representations relative to objects and places but are specifically impaired in their ability to update rapidly and flexibly spatial information that is essential to guide goal-directed actions.     

A 5-month period of epilepsy impairs spatial memory, decreases anxiety, but spares object recognition in the lithium-pilocarpine model in adult rats

PURPOSE: In temporal lobe epilepsy (TLE), interictal behavioral disorders affect patients' quality of life. Therefore we studied long-term behavioral impairments in the lithium-pilocarpine (li-pilo) model of TLE. METHODS: Eleven li-pilo adult rats exhibiting spontaneous recurrent seizures (SRSs) during 5 months were compared with 11 li-saline rats. Spatial working memory was tested in a radial arm maze (RAM), anxiety in an elevated plus-maze (EPM), and nonspatial working memory in an object-recognition paradigm. Neuronal loss was assessed on thionine brain sections after behavioral testing. RESULTS: In the RAM, the time to complete each session and the number of errors per session decreased over a 5-day period in li-saline rats but remained constant and significantly higher in li-pilo rats. In the EPM, the number of entries in and time spent on open arms were significantly higher in li-pilo than li-saline rats. In the object-recognition task, the two groups exhibited a comparable novelty preference for the new object. Neuronal loss reached 47-90% in hilus, CA1, amygdala, and piriform and entorhinal cortex. CONCLUSIONS: In li-pilo rats having experienced SRS for 5 months, performance in the object-recognition task is spared, which suggests that object discrimination remains relatively intact despite extensive damage. Neuronal loss in regions mediating memory and anxiety, such as hippocampus, entorhinal cortex, and amygdala, may relate to impaired spatial orientation and decreased anxiety.     

Preserved learning and memory in mice following chemotherapy: 5-Fluorouracil and doxorubicin single agent treatment, doxorubicin-cyclophosphamide combination treatment

Clinical studies suggest that chemotherapy is associated with long-term cognitive impairment in some patients. A number of underlying mechanisms have been proposed, however, the etiology of chemotherapy-related cognitive dysfunction remains relatively unknown. As part of a multifaceted approach, animal models of chemotherapy induced cognitive impairment are being developed. Thus far, the majority of animal studies have utilized rats, however, mice may prove particularly beneficial in studying genetic risk factors for developing chemotherapy induced cognitive impairment. Thus, C57BL/6J mice were treated once a week for three weeks with saline, doxorubicin and cyclophosphamide (D&C), doxorubicin (Dox), or 5-fluorouracil (5-FU). Recent and remote contextual fear conditioning and novel object recognition (NOR) was assessed. Despite significant toxic effects as assessed by weight loss, the chemotherapy treated mice performed as well as control mice on all task. As are some humans, C57BL/6J mice may be resistant to at least some aspects of chemotherapy induced cognitive decline.     

项目记忆和源记忆的功能磁共振成像研究

目的探讨项目记忆和源记忆的神经基础及其是否存在性别差异。方法健康男女各8名，实验材料为504个高频双汉字词，项目记忆和源记忆实验任务，Block设计，GE1．5T采集功能磁共振成像（mRI）数据，用SPM99分析，得到男女脑功能激活图（P〈0．002，体素块〉20）。结果在P〈0．002，体素块〉20时，女性项目记忆激活双前额叶背外侧BA6（激活数目左右侧分别为62和11个），源记忆较多激活左前额叶背外侧BA6／46（激活数目为59个）；男性项目记忆激活右前额叶背外侧BA6／46（激活数目为64个），源记忆激活双前额叶背外侧BA6（左右侧分别为9和40个）。结论项目记忆更多激活右侧前额叶背外侧，而源记忆更多激活左侧前额叶背外侧。女性较多地引起左前额叶背外侧激活；而男性较多地引起右前额叶背外侧激活。