Long-term exposure to environmental enrichment since youth prevents recognition memory decline and increases synaptic plasticity markers in aging

Aging-associated brain changes include functional alterations that are usually related with memory decline. Epidemiological reports show that a physically and intellectually active life provides a protective effect on this decline and delays the onset of several neurodegenerative diseases. The cellular mechanisms behind the behavioral-based therapies, such as environmental enrichment (EE) exposure, as a method for alleviating age-related memory impairments, are still unknown. Although some reports have shown the benefits of EE exposure in cognitive outcomes in old mice and in animals with experimental neurodegenerative conditions, the effects of lifelong animal exposure to EE have not been explored in detail. In the present work we tested in a rat model the effects of intermittent lifelong exposure since youth to EE on behavioral performance, object recognition memory and anxiety level, as well as on some morphological and biochemical markers of brain plasticity such as hippocampal neurogenesis, synaptophysin content and synaptic morphology. We found that environmental factors have a positive impact on short-memory preservation, as well as on the maintenance of synapses and in the increase in number of new generated neurons within the hippocampus during aging.     

Motor simulation in verbal knowledge acquisition

Recent research highlights the importance of motor processes for a wide range of cognitive functions such as object perception and language comprehension. It is unclear, however, whether the involvement of the motor system goes beyond the processing of information that is gathered through active action experiences and affects also the representation of knowledge acquired through verbal learning. We tested this prediction by varying the presence of motor interference (i.e., squeezing a ball vs. oddball detection task) while participants verbally acquired functional object knowledge and examined the effects on a subsequent object detection task. Results revealed that learning of functional object knowledge was only impaired when participants performed an effector-specific motor task while training. The present finding of an effector-specific motor interference effect on object learning demonstrates the crucial role of the motor system in the acquisition of novel object knowledge and provides support for an embodied account to perception and cognition.     

Combination Effects of Forced Mild Exercise and GABAB Receptor Agonist on Spatial Learning,Memory, and Motor Activity in Striatum Lesion Rats

Basal ganglia (BG) lesions cause impairments of different mammalian’s movement and cognition behaviors. Motor circuit impairment has a dominant role in the movement disorders. An inhibitory factor in BG is GABA neurotransmitter, which is released from striatum. Lesions in GABAergic neurons could trigger movement and cognition disorders. Previous evidence showed that GABA_B receptor agonist (Baclofen) administration in human improves movement disorders and exercise can improve neurodegenerative and cognitive decline; however, the effects of both Baclofen and mild forced treadmill exercise on movement disorders are not well known. The main objective of this study is to investigate the combined effects of mild forced treadmill exercise and microinjection of Baclofen in the internal Globus Pallidus on striatum lesion-induced impairments of spatial learning and motor activity. We used Morris water maze and open filed tests for studying spatial learning, and motor activity, respectively. Results showed that mild exercise and Baclofen microinjection could not lonely affect the spatial learning, and motor activity impairments while the combination of them could alleviate spatial learning, and motor activity impairments in striatum-lesion animals. Our results suggest that striatum lesion-induced memory and motor activity impairments can improve with combination interaction of GABA_B receptor agonist and exercise training.     

Life-long environmental enrichment differentially affects the mnemonic response to estrogen in young, middle-aged, and aged female mice

The present study was designed to examine whether life-long exposure to standard or enriched housing affects the ability of estrogen to improve spatial and object memory throughout the lifespan. Three-week-old female mice were maintained in standard or enriched housing up to and through ovariectomy and behavioral testing at 5, 17, or 22 months of age. Spatial memory was tested in the Morris water maze and object memory was tested using an object recognition task. Immediately after training each day, mice were injected intraperitoneally with vehicle or 0.2 mg/kg 17beta-estradiol. Among young females, object recognition was enhanced by estradiol alone, an effect that was reduced by enrichment. In contrast, spatial water maze performance was impaired by estradiol alone, but improved by the combination of both estradiol and enrichment. At middle-age, object recognition was enhanced by estradiol or enrichment alone, and the combination of both treatments. Spatial memory in the water maze was also improved by both treatments at middle-age, but the beneficial effects of estradiol were limited to standard-housed females. Finally, whereas enrichment in aged females significantly enhanced performance in both tasks, estradiol had no effect at this age in either task. In total, the data indicate that life-long enrichment can significantly alter the extent to which estradiol affects memory in mice throughout the lifespan. Importantly, the interaction between these treatments is highly dependent on age and type of memory tested.     

When motor congruency modulates immediate memory for objects

In line with the embodied cognition view, some researchers have suggested that our capacity to retain information relies on the perceptual and motor systems used to interact with our environment (Barsalou, 1999; Glenberg, 1997). For instance, the language production architecture would be responsible for the retention of verbal materials such as a list of words (Acheson & MacDonald, 2009). However, evidence for the role of the motor system in object memory is still limited. In the present experiments, participants were asked to retain lists of objects in memory. During encoding, participants had to pantomime an action to grasp (Experiments 1A & 1B) or to use the objects (Experiment 2) that was either congruent or incongruent with the objects to be retained. The results showed that performing an incongruent action impaired memory performance compared to a congruent action. This suggests that motor affordances play a role during object retention. The results are discussed in light of the embodied cognition view.     

Induction and activity-dependent reversal of persistent LTP and LTD in lateral perforant path synapses in vivo

The reversibility of long-term potentiation (LTP) and heterosynaptic long-term depression (LTD) lasting weeks was examined in the lateral perforant path of freely moving adult Sprague-Dawley rats. LTP lasting weeks was rapidly reversed within minutes by high-frequency heterosynaptic stimulation of the medial perforant path, in an N-methyl-D-aspartate receptor-dependent manner. LTP reversal also occurred, albeit more slowly and to a lesser extent, when animals were given 1-3 weeks of overnight exposure to an enriched environment (EE). LTD likewise was reversed upon repeated EE exposure. A covert similarity between the degrees of LTP and LTD reversal was revealed when the small potentiation effect of EE treatment by itself on lateral path responses was taken into account. Despite its ability to reverse previously acquired synaptic plasticity, two weeks of EE treatment had no effect on animals' retention of the platform location in a spatial watermaze task, although it did facilitate new learning. These data are in agreement with the hypothesis that hippocampal synapses retain the capacity for rapid synaptic change even when otherwise relatively stable plasticity has previously been induced. Slow reversal of such plasticity did not correlate with a loss of memory retention, possibly because either slow changes permit reorganization of representations such that both old and new information can be accommodated, or else the new information is synaptically represented in orthogonal fashion to the old information.     

The novel object recognition memory: neurobiology, test procedure, and its modifications

Animal models of memory have been considered as the subject of many scientific publications at least since the beginning of the twentieth century. In humans, memory is often accessed through spoken or written language, while in animals, cognitive functions must be accessed through different kind of behaviors in many specific, experimental models of memory and learning. Among them, the novel object recognition test can be evaluated by the differences in the exploration time of novel and familiar objects. Its application is not limited to a field of research and enables that various issues can be studied, such as the memory and learning, the preference for novelty, the influence of different brain regions in the process of recognition, and even the study of different drugs and their effects. This paper describes the novel object recognition paradigms in animals, as a valuable measure of cognition. The purpose of this work was to review the neurobiology and methodological modifications of the test commonly used in behavioral pharmacology.     

儿童早期精细动作技能与认知发展的关系

精细动作技能指个体主要凭借手以及手指等部位的小肌肉或小肌肉群而产生的运动, 它可以为个体提供认知经验, 丰富认知对象, 进而促进个体对事物本质的认识。当个体需要将认知资源-注意在两个或多个任务之间进行分配时, 熟练的精细动作可以节省注意资源, 为高级的认知任务更好地服务; 精细动作与认知在发展中不断相互促进, 有些动作是某些认知习得或认知练习的先决条件; 精细动作技能可以预测小学低年级的学业成绩, 尤其是阅读和数学成绩。精细动作技能和认知发展的关系具有大脑神经发育基础, 它们在某种程度上共享相同的脑区, 如小脑和前额叶。因此, 某些认知损伤的病症可以通过精细动作的训练而得到改善和治疗。     

Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex

Several lines of evidence suggest that extracellular signal-regulated kinase1/2 (ERK1/2) and dopaminergic system is involved in learning and memory. However, it remains to be determined if the dopaminergic system and ERK1/2 pathway contribute to cognitive function in the prefrontal cortex (PFC). The amount of phosphorylated ERK1/2 was increased in the PFC immediately after exposure to novel objects in the training session of the novel object recognition test. An inhibitor of ERK kinase impaired long-term recognition memory 24 h after the training although short-term memory tested 1 h after the training was not affected by the treatment. The dopamine D1 receptor agonist increased ERK1/2 phosphorylation in the PFC in vivo as well as in cortical neurons in vitro. Microinjection of the dopamine D1 receptor antagonist into the PFC impaired long-term recognition memory whereas the D2 receptor antagonist had no effect. Immunohistochemistry revealed that exposure to novel objects resulted in an increase in c-Fos expression in the PFC. Microinjection of the protein synthesis inhibitor anisomycin into the PFC impaired the long-term recognition memory. These results suggest that the activation of ERK1/2 following the stimulation of dopamine D1 receptors is necessary for the protein synthesis-dependent long-term retention of recognition memory in the PFC.     

Captured by motion: dance, action understanding, and social cognition

In this review article, we summarize the main findings from empirical studies that used dance-related forms of rhythmical full body movement as a research tool for investigating action understanding and social cognition. This work has proven to be informative about behavioral and brain mechanisms that mediate links between perceptual and motor processes invoked during the observation and execution of spatially–temporally coordinated action and interpersonal interaction. The review focuses specifically on processes related to (a) motor experience and expertise, (b) learning and memory, (c) action, intention, and emotion understanding, and (d) audio-visual synchrony and timing. Consideration is given to the relationship between research on dance and more general embodied cognition accounts of action understanding and social cognition. Finally, open questions and issues concerning experimental design are discussed with a view to stimulating future research on social-cognitive aspects of dance.     

Object representations are biased toward each other through statistical learning

The visual system is remarkably efficient at extracting regularities from the environment through statistical learning. While such extraction has extensive consequences on cognition, it is unclear how statistical learning shapes the representations of the individual objects that comprise the regularities. Here we examine how statistical learning alters object representations. In three experiments, participants were exposed to either random arrays containing objects in a random order, or structured arrays containing object pairs where two objects appeared next to each other in fixed spatial or temporal configurations. After exposure, one object in each pair was briefly presented and participants judged the location or the orientation of the object without seeing the other object in the pair. We found that when an object reliably appeared next to another object in space, it was judged as being closer to the other object in space even though the other object was never presented (Experiments 1 and 2). Likewise, when an object reliably preceded another object in time, its orientation was biased toward the orientation of the other object even though the other object was never presented (Experiment 3). These results demonstrated that statistical learning fundamentally shapes how individual objects are represented in visual memory, by biasing the representation of one object toward its co-occurring partner. Importantly, participants in all experiments were not explicitly aware of the regularities. Thus, the bias in object representations was implicit. The current study reveals a novel impact of statistical learning on object representation: spatially co-occurring objects are represented as being closer in space, and temporally co-occurring objects are represented as having more similar features.     

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.     

The cerebral representation of space: insights from functional imaging data

Functional imaging techniques, such as positron emission tomography and functional magnetic resonance imaging, present a unique opportunity to examine, in humans, the cerebral representation of space in vivo. Space is ubiquitous and not a unitary phenomenon, and the brain uses visual, vestibular and proprioceptive inputs to produce multiple representations of space subserving spatial cognition, ranging from gaze control to remembering multiple complex large-scale environments. Functional imaging studies have shown the importance of the parietal cortex in perceptual, motor, attention and working memory aspects of body-centred human spatial cognition. Functional imaging has also revealed pathways in humans homologous to those found in monkeys for the separate processing of spatial location and object identity. There are further suggestions of similar differentiation in working memory. The importance of the medial temporal region in the recall of spatial location has been confirmed also and novel virtual reality paradigms are now providing insights into the cerebral representation of spatially-extended large-scale environments. We still have much to learn about the cerebral representation of space in the human brain and functional brain imaging, in concert with patient studies and animal models, will allow us to continue investigating.     

Infusion of protein synthesis inhibitors in the entorhinal cortex blocks consolidation but not reconsolidation of object recognition memory

Memory consolidation and reconsolidation require the induction of protein synthesis in some areas of the brain. Here, we show that infusion of the protein synthesis inhibitors anisomycin, emetine and cycloheximide in the entorhinal cortex immediately but not 180 min or 360 min after training in an object recognition learning task hinders long-term memory retention without affecting short-term memory or behavioral performance. Inhibition of protein synthesis in the entorhinal cortex after memory reactivation involving either a combination of familiar and novel objects or two familiar objects does not affect retention. Our data suggest that protein synthesis in the entorhinal cortex is necessary early after training for consolidation of object recognition memory. However, inhibition of protein synthesis in this cortical region after memory retrieval does not seem to affect the stability of the recognition trace.     

Neurocognitive control in dance perception and performance

Dance is a rich source of material for researchers interested in the integration of movement and cognition. The multiple aspects of embodied cognition involved in performing and perceiving dance have inspired scientists to use dance as a means for studying motor control, expertise, and action-perception links. The aim of this review is to present basic research on cognitive and neural processes implicated in the execution, expression, and observation of dance, and to bring into relief contemporary issues and open research questions. The review addresses six topics: 1) dancers' exemplary motor control, in terms of postural control, equilibrium maintenance, and stabilization; 2) how dancers' timing and on-line synchronization are influenced by attention demands and motor experience; 3) the critical roles played by sequence learning and memory; 4) how dancers make strategic use of visual and motor imagery; 5) the insights into the neural coupling between action and perception yielded through exploration of the brain architecture mediating dance observation; and 6) a neuroesthetics perspective that sheds new light on the way audiences perceive and evaluate dance expression. Current and emerging issues are presented regarding future directions that will facilitate the ongoing dialog between science and dance.     

Distinguishing the neural correlates of episodic memory encoding and semantic memory retrieval

Episodic memory and semantic memory interact very closely. In particular, episodic memory encoding (EE) tends to elicit semantic memory retrieval (SR), and vice versa. Thus, similar activations for EE and SR in functional neuroimaging studies may reflect shared memory processes, or they may reflect the fact that EE and SR are usually confounded. To address this issue, we used a factorial functional magnetic resonance imaging approach to disentangle the neural correlates of EE and SR. Within the left temporal lobe, the hippocampus was associated with successful EE, whereas a posterior lateral region was associated with successful SR. Within the left inferior prefrontal cortex, a posterior region was involved in SR, a mid region was involved in both SR and EE, and an anterior region was involved in EE, but only when SR was also high. Thus, the neural correlates of EE and SR are dissociable but interact in specific brain regions.     

A motor similarity effect in object memory

In line with theories of embodied cognition (e.g., Versace et al. European Journal of Cognitive Psychology, 21, 522–560, 2009), several studies have suggested that the motor system used to interact with objects in our environment is involved in object recognition (e.g., Helbig, Graf, & Kiefer Experimental Brain Research, 174, 221-228, 2006). However, the role of the motor system in immediate memory for objects is more controversial. The objective of the present study was to investigate the role of the motor system in object memory by manipulating the similarity between the actions associated to series of objects to be retained in memory. In Experiment 1, we showed that lists of objects associated to dissimilar actions were better recalled than lists associated to similar actions. We then showed that this effect was abolished when participants were required to perform a concurrent motor suppression task (Experiment 2) and when the objects to be memorized were unmanipulable (Experiment 3). The motor similarity effect provides evidence for the role of motor affordances in object memory.     

Posttraining activation of CB1 cannabinoid receptors in the CA1 region of the dorsal hippocampus impairs object recognition long-term memory

Evidence indicates that brain endocannabinoids are involved in memory processing. However, the participation of CB1 and CB2 cannabinoid receptors in recognition memory has not been yet conclusively determined. Therefore, we evaluated the effect of the posttraining activation of hippocampal cannabinoid receptors on the consolidation of object recognition memory. Rats with infusion cannulae stereotaxically aimed to the CA1 region of the dorsal hippocampus were trained in an object recognition learning task involving exposure to two different stimulus objects. Memory retention was assessed at different times after training. In the test sessions, one of the objects presented during training was replaced by a novel one. When infused in the CA1 region immediately after training, the non-selective cannabinoid receptor agonist WIN-55,212-2 and the endocannabinoid membrane transporter inhibitor VDM-11 blocked long-term memory retention in a dose-dependent manner without affecting short-term memory, exploratory behavior, anxiety state or the functionality of the hippocampus. The amnesic effect of WIN-55,212-2 and VDM-11 was not due to state-dependency and was completely reversed by co-infusion of the CB1 receptor antagonist AM-251 and mimicked by the CB1 receptor agonist ACEA but not by the CB2 receptor agonists JWH-015 and palmitoylethanolamide. Our data indicate that activation of hippocampal CB1 receptors early after training hampers consolidation of object recognition memory.     

Brain regions involved in subprocesses of small-space episodic object-location memory: a systematic review of lesion and functional neuroimaging studies

Object-location memory (OLM) enables us to keep track of the locations of objects in our environment. The neurocognitive model of OLM (Postma, A., Kessels, R. P. C., & Van Asselen, M. (2004). The neuropsychology of object-location memory. In G. L. Allen (Ed.), Human spatial memory: Remembering where (pp. 143–160). Mahwah, NJ: Lawrence Erlbaum, Postma, A., Kessels, R. P. C., & Van Asselen, M. (2008). How the brain remembers and forgets where things are: The neurocognition of object-location memory. Neuroscience & Biobehavioral Reviews, 32, 1339–1345. doi:10.1016/j.neubiorev.2008.05.001) proposes that distinct brain regions are specialised for different subprocesses of OLM (object processing, location processing, and object-location binding; categorical and coordinate OLM; egocentric and allocentric OLM). It was based mainly on findings from lesion studies. However, recent episodic memory studies point to a contribution of additional or different brain regions to object and location processing within episodic OLM. To evaluate and update the neurocognitive model of OLM, we therefore conducted a systematic literature search for lesion as well as functional neuroimaging studies contrasting small-space episodic OLM with object memory or location memory. We identified 10 relevant lesion studies and 8 relevant functional neuroimaging studies. We could confirm some of the proposals of the neurocognitive model of OLM, but also differing hypotheses from episodic memory research, about which brain regions are involved in the different subprocesses of small-space episodic OLM. In addition, we were able to identify new brain regions as well as important research gaps.     

睡眠对恐惧学习的影响及其认知神经机制

睡眠问题可能会诱发恐惧相关情绪障碍(焦虑、创伤性应激障碍、恐怖症等),研究睡眠影响恐惧学习的认知神经机制,有助于增强对恐惧相关情绪障碍的预测、诊断和治疗。以往研究表明睡眠剥夺影响恐惧习得和消退主要是通过抑制vmPFC活动,阻碍其与杏仁核的功能连接,从而导致恐惧习得增强或是消退学习受损。进一步研究发现睡眠不同阶段对恐惧学习相关脑区有独特的影响:剥夺(缺乏)快速眼动睡眠会抑制vmPFC活动、增强杏仁核、海马激活,导致恐惧习得增强,消退学习受损,此外边缘皮层的功能连接减少破坏了记忆巩固(恐惧记忆和消退记忆);而慢波睡眠主要与海马变化有关,慢波睡眠期间进行目标记忆重激活可促进恐惧消退学习。未来研究需要增加睡眠影响恐惧泛化的神经机制研究、及昼夜节律中断对恐惧消退的影响,以及关注动物睡眠研究向人类睡眠研究转化中存在的问题。