Unpredictable chronic stress in juvenile or adult rats has opposite effects, respectively, promoting and impairing resilience

We evaluated the effects of early maternal deprivation (MD; age 7-14 days) alone or in combination with unpredictable chronic stress (UCS; MDUN; 28-84 days) on anxiety and learning in 90 days old adult rats. We hypothesized that exposure to both stressors (MDUN) would be more detrimental than exposure to one or neither. Unexpectedly, adult rats from the MDUN group did not differ from control animals, whereas adult MD animals exhibited impaired avoidance learning. We next investigated the effect of juvenile-onset (30-90 days) versus adult-onset (60-90 days) stress on avoidance learning in adulthood (90 days). We found that adult-onset chronic stress impaired avoidance learning and memory whereas juvenile-onset stress did not. Thus, the results again indicate that juvenile exposure to UCS induces resilience rather than impairment.     

Intracerebroventricular effects of angiotensin II on a step-through passive avoidance task in rats

A wealth of evidence indicates that angiotensin II (Ang II) is involved in learning and memory. However, the precise role of this peptide in these cognitive processes is still controversial, with data indicating either an inhibitory or an enhancing action. The present study was designed to further investigate the effects of intracerebroventricular injections of Ang II (0.5, 1 or 3nmol/5microl) on a step-through passive avoidance task in male adult Wistar rats. When administered pretraining, Ang II did not affect the acquisition of passive avoidance, but markedly improved avoidance performance when given before the retrieval test. The latter effect was observed in retest sessions performed up to 72h after training. Administration of the peptide five minutes after training impaired retention of inhibitory avoidance. Therefore, Ang II may exert opposite effects on passive avoidance memory according to its interference with brain mechanisms leading to the storage or retrieval of this aversively motivated task.     

Effects of emotion and age on performance during a think/no-think memory task

Recent studies have demonstrated that young adults can voluntarily suppress information from memory when directed to. After learning novel word pairings to criterion, participants are shown individual words and instructed either to "think" about the associated word, or to put it out of mind entirely ("no-think"). When given a surprise cued recall test, participants typically show impaired recall for no-think words relative to think or "control" (un-manipulated) words. The present study investigated whether this controlled suppression effect persists in an aged population, and examined how the emotionality of the to-be-suppressed word affects suppression ability. Data from four experiments using the think/no-think task demonstrate that older and younger adults can suppress information when directed to (Experiment 1), and the age groups do not differ significantly in this ability. Experiments 2 through 4 demonstrate that both age groups can suppress words that are emotional (positive or negative valence) or neutral. The suppression effect also persists even if participants are tested using independent probe words that are semantically related to the target words but were not the studied cue words (Experiments 3 and 4). These data suggest that the cognitive functioning necessary to suppress information from memory is present in older adulthood, and that both emotional and neutral information can be successfully suppressed from memory.     

Learning strategy is influenced by trait anxiety and early rearing conditions in prepubertal male, but not prepubertal female rats

Rodents solve dual-solution tasks that require navigation to a goal by adopting either a hippocampus-dependent place strategy or a striatum-dependent stimulus-response strategy. A variety of factors, including biological sex and emotional status, influence the choice of learning strategy. In these experiments, we investigated the relationship between learning strategy and anxiety level in male and female rats prior to the onset of puberty, before the activational effects of gonadal hormones influence these processes. In the first experiment, prepubertal male rats categorized as high in trait anxiety at 26days of age exhibited a bias toward stimulus-response strategy at 28days of age, whereas age-matched females exhibited no preference in strategy regardless of anxiety level. In the second experiment, male and female rats were separated from their dams for either 15 or 180min per day during the first 2weeks of life and tested on a battery of anxiety and cognitive tasks between 25 and 29days of age. Prolonged maternal separations for 180min were associated with impaired spatial memory on a Y-maze task in both prepubertal males and females. Furthermore, prolonged maternal separations were linked to elevated anxiety and a bias for stimulus-response strategy in prepubertal males but not females. Alternatively, brief separations from dams for 15min were associated with intact spatial memory, lower levels of anxiety, and no preference for either learning strategy in both sexes. These results provide evidence of sex-specific effects of trait anxiety and early maternal separation on the choice of learning strategy used by prepubertal rodents.     

Emotional and cognitive information processing: relations to behavioral performance and hippocampal long-term potentiation in vivo during a spatial water maze training in rats

Emotionality as well as cognitive abilities contribute to the acquisition and retrieval of memories as well as to the consolidation of long-term potentiation (LTP), a cellular model of memory formation. However, little is known about the timescale and relative contribution of these processes. Therefore, we tested the effects of weak water maze training, containing both emotional and cognitive demands, on LTP in the hippocampal dentate gyrus. The population spike amplitude (PSA)-LTP was prolonged in all rats irrespective of whether they memorized the platform position or not, whereas the field excitatory postsynaptic potential (fEPSP)-LTP was impaired in good learners and enhanced in poor learners. We then dissociated the behavioral performance of rats during the water maze task by principal component analysis and by means of stress hormone concentrations into underlying "emotional" and "cognitive" factors. PSA-LTP was associated with "emotional" and fEPSP-LTP with "cognitive" behavior. PSA-LTP was depotentiated after the blockade of corticosterone binding mineralocorticoid receptors (MRs) in trained animals, while fEPSP-LTP was unaffected. These results suggest that synaptic processing and encoding of emotional information in the hippocampal dentate gyrus is realized fast and further information transfer is detectable by the reinforcement of PSA-LTP, whereas that of cognitive memories is long lasting.     

Memory training interventions require a tailor-made approach: Commentary on McDaniel and Bugg

Memory training for older adults often produces gains that are limited to the particular memory tasks encountered during training. We suggest that memory training programs may be misguided by an implicit "generalist" assumption-memory training on a couple of memory tasks will have a positive benefit on memory ability in general. One approach to increase memory-training benefits is to target training for the everyday memory tasks for which older adults struggle. Examples include training retrieval strategies, prospective memory strategies, and strategies for learning and remembering names. Another approach is to design training to foster transfer. Possible elements to improve transfer are increasing the variation that is experienced during the course of training at the level of stimuli and tasks, incorporating "homework" that guides the older adult to become attuned to situations in which the strategies can be applied, and providing older adults with a better understanding of how memory works. Finally, incorporating aerobic exercise into memory training programs may potentiate the acquisition and maintenance of the trained cognitive strategies.     

Effects of combined treatment with vitamins C and E on passive avoidance learning and memory in diabetic rats

Learning and memory deficits occur in diabetes mellitus. Although the pathogenesis of cognitive impairment in diabetes has not been fully elucidated, factors such as metabolic impairments, vascular complications and oxidative stress are thought to play possible roles. Here we investigated the effect of chronic treatment with vitamin C (50 mg/kg, p.o), vitamin E (100 mg/kg, p.o) and both together on passive avoidance learning (PAL) and memory in male Wistar control and diabetic rats. Treatments were begun at the onset of hyperglycemia. Passive avoidance learning was assessed 30 days later. Retention was tested 24 h after training. At the end, animals were weighed and blood samples were drawn for plasma glucose measurement. Diabetes caused impairment in acquisition and retrieval processes of PAL and memory. The combination of vitamin C and E improved learning and memory in controls and reversed learning and memory deficits in diabetic rats. Combined treatment also affected the body weight and plasma glucose level of diabetic treated animals compared to untreated diabetic animals. Hypoglycemic effects and antioxidant properties of the vitamins may be involved in the nootropic effect of such treatment. These results show that combined treatment with vitamins C and E improved PAL and memory of control rats. In addition, combined vitamins administration to rats for 30 days from onset of diabetes alleviated the negative influence of diabetes on learning and memory. Therefore, combined vitamins treatment may provide a new potential alternative for prevention of impaired cognitive functions associated with diabetes and may warrant further clinical study.     

Early maternal availability and prefrontal correlates of reward-related memory

Early emotional experiences affect developing brain systems that subsequently mediate adult learning and memory in rodents. Here we test for similar effects in squirrel monkeys (Saimiri sciureus) four years after disruptions in early maternal availability. These conditions were previously shown to generate differences in emotional behavior, hypothalamic-pituitary-adrenal stress physiology, and right ventral medial prefrontal volumes determined in adulthood by magnetic resonance imaging. This report identifies in the same monkeys variability in reward-related memory on tests with a spatial reversal. Adult monkeys that more often selected locations repeatedly rewarded before each reversal had larger right ventral medial prefrontal volumes, but not hippocampal nor dorsolateral prefrontal volumes on the left or right brain side. Differences in performance were also discerned after each spatial reversal. These findings indicate that maternal availability alters developing ventral medial prefrontal brain regions involved in reward-related memory.     

Learning to avoid in older age

The dopamine hypothesis of aging suggests that a monotonic dopaminergic decline accounts for many of the changes found in cognitive aging. The authors tested 44 older adults with a probabilistic selection task sensitive to dopaminergic function and designed to assess relative biases to learn more from positive or negative feedback. Previous studies demonstrated that low levels of dopamine lead to avoidance of those choices that lead to negative outcomes, whereas high levels of dopamine result in an increased sensitivity to positive outcomes. In the current study, age had a significant effect on the bias to avoid negative outcomes: Older seniors showed an enhanced tendency to learn from negative compared with positive consequences of their decisions. Younger seniors failed to show this negative learning bias. Moreover, the enhanced probabilistic integration of negative outcomes in older seniors was accompanied by a reduction in trial-to-trial learning from positive outcomes, thought to rely on working memory. These findings are consistent with models positing multiple neural mechanisms that support probabilistic integration and trial-to-trial behavior, which may be differentially impacted by older age.     

Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement.     

Amygdala and "emotional" modulation of the relative use of multiple memory systems

The basolateral amygdala modulates the cognitive and habit memory processes mediated by the hippocampus and caudate nucleus, respectively. The present experiments used a plus-maze task that can be acquired using either hippocampus-dependent "place" learning or caudate-dependent "response" learning to examine whether peripheral or intra-basolateral amygdala injection of anxiogenic drugs would bias rats towards the use of a particular memory system. In Experiment 1, adult male Long-Evans rats were trained to swim from the same start point to an escape platform located in a consistent goal arm, and received pre-training peripheral injections of the alpha(2)-adrenoceptor antagonists yohimbine (2.5 or 5.0 mg/kg), RS 79948-197 (0.05, 0.1, or 0.2 mg/kg), or vehicle. On a drug-free probe trial from a novel start point administered 24h following acquisition, vehicle treated rats predominantly displayed hippocampus-dependent place learning, whereas rats previously treated with yohimbine (2.5, 5.0 mg/kg) or RS 79948-197 (0.1 mg/kg) predominantly displayed caudate-dependent response learning. In Experiment 2, rats receiving pre-training intra-basolateral amygdala infusions of RS 79948-197 (0.1 microg/0.5 microl) also predominantly displayed response learning on a drug-free probe trial. The findings indicate (1) peripheral injections of anxiogenic drugs can influence the relative use of multiple memory systems in a manner that favors caudate-dependent habit learning over hippocampus-dependent cognitive learning, and (2) intra-basolateral amygdala infusion of anxiogenic drugs is sufficient to produce this modulatory influence of emotional state on the use of multiple memory systems.     

年龄、作业难度和训练对成人记忆的影响

采用“联想学习”、“图象自由回忆”和“附加联想”三项目,对９０例成人（分为青年、老年和老老年组各３０例）进行记忆测查和训练,目的为探讨年龄,作业难度和训练对记忆的影响。结果表明：青年组记忆成绩明显高于老年和老老年组,后两组无显著差异;无关联想的年龄差异大于有关联想,作业难度扩大了年龄差异;各年龄组训练后记忆得到明显改善,并且训练扩大了年龄和作业易难的差异。由此可见,记忆受年龄、作业难度和训练三因素的相互作用,也再次证实了老年认知功能具有一定的可塑性。     

Androgens' effects to enhance learning may be mediated in part through actions at estrogen receptor-beta in the hippocampus

Testosterone (T) may enhance cognitive performance. However, its mechanisms are not well understood. First, we hypothesized that if T's effects are mediated in part through actions of its 5alpha-reduced metabolites, dihydrotestosterone (DHT) and/or 3alpha-androstanediol (3alpha-diol) in the hippocampus, then T, DHT, and 3alpha-diol-administration directly to the hippocampus should enhance learning and memory in the inhibitory avoidance task. In order to test this hypothesis, gonadectomized (GDX) male rats were administered T, DHT, or 3alpha-diol via intrahippocampal inserts immediately following training in the inhibitory avoidance task. We found that T tended to increase, and DHT and 3alpha-diol significantly increased, performance in the inhibitory avoidance task compared to vehicle-administered GDX rats. Second, we hypothesized that, if androgens' effects are due in part to actions of 3alpha-diol in the hippocampus, then systemic or intrahippocampal administration of 3alpha-diol should significantly enhance cognitive performance of GDX male rats. Third, we hypothesized that, if androgen metabolites can have actions at estrogen receptors (ERs) in the hippocampus, then administration of ER antisense oligonucleotides (AS-ODNs) directly to the hippocampus of GDX, 3alpha-diol replaced, rats would decrease learning in the inhibitory avoidance task. We found that intrahippocampal administration of AS-ODNs for ERbeta, but not ERalpha, significantly decreased learning and memory of 3alpha-diol replaced rats. Together, these findings suggest that T's effects to enhance learning and memory may take place, in part, through actions of its metabolite, 3alpha-diol, at ERbeta in the dorsal hippocampus.     

儿童2岁时情绪调节策略预测4岁时社会行为

考察儿童情绪调节的早期发展对以后社会行为的预测。对 176名儿童进行 2年追踪 :2岁时 ,观察他们在陌生情境和延迟满足情境下的情绪调节策略。 4岁时 ,对他们在陌生同伴情境中的自由游戏活动进行观察 ,评价其社会交往能力和社会退缩性。在儿童完成分车票任务和收拾玩具过程中对其任务坚持性进行评价。通过回归分析我们发现在预测 4岁时社会行为上早期情绪调节策略的主效应显著。这表明 2岁时的情绪调节策略能显著地预测儿童 4岁时的社会行为     

Comparison of Cognitive Empathy,Emotional Empathy,and Social Functioning in Different Age Groups

Empathic responses and optimum social functioning are associated with psychological and physical health benefits. The aim of this study was to compare emotional empathy, cognitive empathy, and social functioning among different age groups, including adolescence, young adulthood, middle adulthood, and late adulthood. One hundred and ninety‐six people (92 males, 104 females) with the age range of 14 to 85 assigned to four age groups (adolescents, young adults, middle adults, and older adults) participated in this study. Participants were asked to complete the Empathy Quotient, the Revised Eyes Test, and Social Functioning Scale. The results showed that there were significant differences between older adults and other groups. Emotional empathy increased in older people, but there were deficits in some aspects of cognitive empathy. Also, the findings showed an age‐related decline in social functioning. Due to deficits in cognitive empathy affected by ageing, older adults showed some impairment in their ability to interpret emotional cues. This age‐related decline in cognitive empathy might be a reason for weak social functioning in older adults. Therefore, considering these elements would be helpful to provide healthcare strategies for elderly people.     

MK-801 improves retention in aged rats: implications for altered neural plasticity in age-related memory deficits

Alterations in N-methyl-d-aspartate receptor (NMDAR)-dependent synaptic plasticity, characteristic of aged rodents, may contribute to impaired memory with advanced age. The purpose of the current research was to examine whether NMDARs contribute to rapid forgetting on a spatial memory task. Aged (22-24 months) and adult (3-6 months) male Fischer 344 rats received 18 training trials, over a period of 3 to 4 h, on the spatial version of the Morris water maze. Immediately after training, a standard free-swim probe trial was administered to assess the acquisition of spatial bias, which was determined by the percent of time spent in the goal quadrant and the number of platform crossings. Rats then received injections of the noncompetitive NMDAR antagonist, (+)-10, 11-dihydro-5methyl-5H-dibenzo(a,b)cycloheptene-5,10 imine (MK-801, 0. 05 mg/kg, i.p.), or a vehicle injection of equal volume. Approximately 24 h later, rats were administered a second free-swim probe trial to assess retention of spatial bias. All age/drug groups exhibited a spatial bias on the acquisition probe, with adults generally outperforming the aged rats. On the retention probe, this spatial bias continued to be shown by adult rats, regardless of treatment. For the aged group, in contrast, only MK-801-injected rats maintained a spatial bias on the retention probe, suggesting that NMDAR activity may be involved in rapid forgetting during aging. Because blockade of NMDARs also may impair new learning, which may, in turn, protect previously stored information from retroactive interference, rats in a second experiment received post-training injections of scopolamine (0.05 mg/kg), a compound known to inhibit learning. However, scopolamine did not enhance retention in the aged group, consistent with the hypothesis that MK-801 influenced memory in aged rats through its actions on NMDAR-dependent synaptic plasticity.     

基于即时反馈的反应抑制训练对青少年和成人执行功能的训练效应和迁移效应

本研究以基于即时反馈的Stop Signal范式为训练任务, 考察3周训练是否对青少年和成人的执行功能产生训练效应和迁移效应。发现青少年、成人实验组和积极控制组都出现了训练效应。两个实验组均产生了对反应抑制Go/No-go任务的迁移效应; 但只有青少年实验组出现了对干扰抑制Stroop任务的迁移效应。成人实验组和积极控制组都出现了对2-back任务的迁移效应; 但只有青少年实验组出现了在2-和3-back任务上的迁移效应。所有组别都未能出现对推理能力的迁移。研究证明从青春期到成年期, 基于即时反馈的反应抑制训练能够对执行功能产生训练和迁移效应, 但迁移仅限于抑制和工作记忆等基础成分, 无法改善推理能力。     

The effects of estradiol on avoidance learning in ovariectomized adult rats

The present study examined the effects of ovariectomy and subsequent estradiol replacement on learning in young adult rats using a set of instrumental avoidance paradigms differing in the nature and extent of prior experience in the learning context. Thus, one group of animals was placed directly into avoidance learning (AV). A second group was trained on an appetitive task first, and then transferred into the aversive context (AP-AV). The third group was exposed to the training context without any specific appetitive response requirement, and then required to learn an active avoidance response (Context-AV). We found that estradiol (OVX+E) impaired avoidance acquisition in all cases relative ovariectomized controls (OVX). In contrast, while avoidance learning is improved following appetitive training or context exposure in both OVX+E and OVX animals, the OVX+E animals profit to a greater extent from the appetitive or context experience than do the OVX controls. We suggest that this difference may be due to enhanced attentional processes or improved hippocampal processing of contextual factors. Thus, estradiol negatively influences simple associative avoidance learning in ovariectomized rats, but appears to promote positive transfer.     

Phthalic acid amygdalopetal lesion of the nucleus basalis magnocellularis induces reversible memory deficits in rats

The basolateral amygdala (BLA) is extensively implicated in emotional learning and memory. The current study investigated the contribution of cholinergic afferents to the BLA from the nucleus basalis magnocellularis in influencing aversive learning and memory. Sprague-Dawley rats were given permanent unilateral phthalic acid (300 ng) lesions of the nucleus basalis magnocellularis and were chronically implanted with cannulas aimed at the ipsilateral BLA. Lesioned rats showed a pronounced inhibitory avoidance task retention deficit that was attenuated by acute posttraining infusions of the muscarinic cholinergic agonist oxotremorine (4 ng) or the indirect agonist physostigmine (1 microg) into the BLA. Continuous multiple-trial inhibitory avoidance training and testing revealed that lesioned rats have a mild acquisition deficit, requiring approximately 1 additional shock to reach the criterion, and a pronounced consolidation deficit as indicated by a shorter latency to enter the shock compartment on the retention test. Because lesioned rats did not differ from sham-operated controls in performance on a spatial water maze task or in shock sensitivity, it is not likely that the memory impairments produced by the phthalic acid lesions are due to any general sensory or motor deficits. These findings suggest that the dense cholinergic projection from the nucleus basalis magnocellularis to the BLA is involved in both the acquisition and the consolidation of the aversive inhibitory avoidance task.     

Age-related changes in working and reference memory performance and locomotor activity in the Wistar rat

Wistar rats of three age groups were tested in an automated tunnel-maze system of variable geometry to investigate whether changes in spontaneous locomotor activity and in learning and memory develop differentially or in a correlated fashion as a function of age. Senescent (30 months) as well as mature-adult (17 months) rats showed an age-correlated decline of locomotor activity as compared to the mature-young (5 months) group. Both working-memory (measured as within-trial arm discrimination performance) and reference-memory (measured as avoidance of "blind alley" visits) were severely affected in the senescent group, whereas the middle-aged animals suffered only from a working-memory deficit. The findings provide evidence that locomotor deficits do not necessarily interfere in the assessment of age-related changes in cognitive performance. Furthermore the results support the hypothesis that working and reference memory have different underlying physiological correlates and that these neuronal systems are differentially affected by the aging process.