Differential involvement of hippocampal calcineurin during learning and reversal learning in a Y-maze task

The regulation and function of the calcium-dependent phosphatase calcineurin (CaN, protein phosphatase 2B) in learning and memory remain unclear, although recent work indicates that CaN may play a differential role in training and reversal training. To gain more insight into the involvement of CaN in these two types of learning, hippocampal CaN activity, protein levels, and expression patterns were studied in mice subjected to a reference memory version of the Y-maze task. We show that (1) training but not habituation induces a decrease in cytosolic CaN activity, (2) the recovery of cytosolic CaN activity is reversal training specific and does not reflect normal restoration of basal levels unrelated to subsequent learning, (3) cytosolic protein levels for the catalytic subunit of CaN (CaNA) are decreased at the early phase of training, but not at the early phase of reversal training, (4) CaNA immunoreactivity in the dorsal hippocampus is enhanced in the CA1 and CA3 area (but not in the dentate gyrus [DG] or subiculum [SUB]) only during reversal training. These findings indicate that memory formation is accompanied by reduced CaN activity, whereas adapting to changes in a familiar environment is accompanied by restored CaN activity. Moreover, reversal training selectively affects hippocampal CA3 and CA1 regions, suggesting a specific function of these hippocampal subregions in reversal learning.     

Effects of partial avoidance and punishment contingencies on shuttlebox-avoidance learning in Fischer 344 rats

An unsignaled, escapable shock was presented contingent on an avoidance response. Fischer 344 rats responded less to the warning signal in proportion to its temporal distance from the avoidance response. Partial contingency effects were further obtained by variation in the instrumental conditioning space for an aversive stimulus. However, the arbitrary omission of an imminent shock on half the trial in which the rats failed to avoid a shock, led to little avoidance acquisition, and shock-frequency reduction was thus not sufficient to produce the acquisition of the avoidance response. Because early avoidance responses were initiated by escape from shock, a stimulus contingency may be essential for response initiation, and an explicit response contingency is important in maintaining successful avoidance responses.     

The impact of music on learning and consolidation of novel words

Music can be a powerful mnemonic device, as shown by a body of literature demonstrating that listening to text sung to a familiar melody results in better memory for the words compared to conditions where they are spoken. Furthermore, patients with a range of memory impairments appear to be able to form new declarative memories when they are encoded in the form of lyrics in a song, while unable to remember similar materials after hearing them in the spoken modality. Whether music facilitates the acquisition of completely new information, such as new vocabulary, remains unknown. Here we report three experiments in which adult participants learned novel words in the spoken or sung modality. While we found no benefit of musical presentation on free recall or recognition memory of novel words, novel words learned in the sung modality were more strongly integrated in the mental lexicon compared to words learned in the spoken modality. This advantage for the sung words was only present when the training melody was familiar. The impact of musical presentation on learning therefore appears to extend beyond episodic memory and can be reflected in the emergence and properties of new lexical representations.     

睡眠对知觉与动作序列内隐学习离线巩固效应的影响

离线阶段发生的学习被称为离线巩固, 即在最初获得知识之后, 即使没有额外的练习, 其记忆痕迹也会保持稳定或提高。有研究初步探究了睡眠对知觉和动作序列内隐学习离线巩固的影响, 然而, 这些研究未能实现知觉序列与动作序列的完全分离, 序列类型是否调节睡眠对内隐序列学习离线巩固的影响仍需进一步探讨。此外, 既往外显学习的研究发现相对于简单的序列, 复杂的序列更容易从睡眠中获益, 表现出基于睡眠的离线巩固效应。睡眠对知觉序列与动作序列内隐学习离线巩固的影响是否会受到序列复杂程度的调节尚不明确。为此, 本研究在完全分离知觉序列和动作序列的情况下, 通过3个实验操纵序列的长度及结构, 设置3种不同复杂程度的序列规则, 考察了这一问题。结果发现, 对于动作序列, 序列规则复杂程度较低时, 无论是否经过睡眠都会发生离线巩固效应, 而当动作序列规则较为复杂时, 只有经历睡眠才会引起离线巩固效应; 对于知觉序列, 无论何种难易程度的规则, 均未发生离线巩固效应。上述结果表明内隐序列知识基于睡眠的离线巩固会受到序列类型及序列复杂程度的调节, 这为内隐学习的离线巩固争论提供了新的视角。     

Early boost and slow consolidation in motor skill learning

Motorskill learning is a dynamic process that continues covertly after training has ended and eventually leads to delayed increments in performance. Current theories suggest that this off-line improvement takes time and appears only after several hours. Here we show an early transient and short-lived boost in performance, emerging as early as 5-30 min after training but no longer observed 4 h later. This early boost is predictive of the performance achieved 48 h later, suggesting its functional relevance for memory processes.     

Central galanin administration blocks consolidation of spatial learning

Galanin is a neuropeptide that inhibits the evoked release of several neurotransmitters, inhibits the activation of intracellular second messengers, and produces deficits in a variety of rodent learning and memory tasks. To evaluate the actions of galanin on encoding, consolidation, and storage/retrieval, galanin was acutely administered to Sprague-Dawley rats at time points before and after training trials in the Morris water maze. Intraventricular administration of galanin up to 3h after subjects had completed daily training trials in the Morris water task impaired performance on the probe trial, indicating that galanin-blocked consolidation. Pretreatment with an adenylate cyclase activator, forskolin, prevented the deficits in distal cue learning produced by galanin. Di-deoxyforskolin, an inactive analog of forskolin, had no effect. These results provide the first evidence that galanin interferes with long-term memory consolidation processes. A potential mechanism by which galanin produces this impairment may involve the inhibition of adenylate cyclase activity, leading to inhibition of downstream molecular events that are necessary for consolidation of long-term memory.     

From acquisition to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning

One of the most rigorously investigated problems in modern neuroscience is to decipher the mechanisms by which experience-induced changes in the central nervous system are translated into behavioral acquisition, consolidation, retention, and subsequent recall of information. Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Recent experimental evidence indicates that BDNF modulates synaptic transmission and plasticity by acting across different spatial and temporal domains. BDNF signaling evokes both short- and long-term periods of enhanced synaptic physiology in both pre- and postsynaptic compartments of central synapses. Specifically, BDNF/TrkB signaling converges on the MAP kinase pathway to enhance excitatory synaptic transmission in vivo, as well as hippocampal-dependent learning in behaving animals. Emerging concepts of the intracellular signaling cascades involved in synaptic plasticity induced through environmental interactions resulting in behavioral learning further support the contention that BDNF/TrkB signaling plays a fundamental role in mediating enduring changes in central synaptic structure and function. Here we review recent literature showing the involvement of BDNF/TrkB signaling in hippocampal-dependent learning paradigms, as well as in the types of cellular plasticity proposed to underlie learning and memory.     

Insulin receptor signaling in long-term memory consolidation following spatial learning

Evidence has shown that the insulin and insulin receptor (IR) play a role in cognitive function. However, the detailed mechanisms underlying insulin's action on learning and memory are not yet understood. Here we investigated changes in long-term memory-associated expression of the IR and downstream molecules in the rat hippocampus. After long-term memory consolidation following a water maze learning experience, gene expression of IR showed an up-regulation in the CA1, but a down-regulation in the CA3 region. These were correlated with a significant reduction in hippocampal IR protein levels. Learning-specific increases in levels of downstream molecules such as IRS-1 and Akt were detected in the synaptic membrane accompanied by decreases in Akt phosphorylation. Translocation of Shc protein to the synaptic membrane and activation of Erk1/2 were also observed after long-term memory formation. Despite the clear memory-correlated alterations in IR signaling pathways, insulin deficits in experimental diabetes mellitus (DM) rats induced by intraperitoneal injections of streptozotocin resulted in only minor memory impairments. This may be due to higher glucose levels in the DM brain, and to compensatory mechanisms from other signaling pathways such as the insulin-like growth factor-1 receptor (IGF-1R) system. Our results suggest that insulin/IR signaling plays a modulatory role in learning and memory processing, which may be compensated for by alternative pathways in the brain when an insulin deficit occurs.     

Patterns of interference in sequence learning and prism adaptation inconsistent with the consolidation hypothesis

The studies reported here used an interference paradigm to determine whether a long-term consolidation process (i.e., one lasting from several hours to days) occurs in the learning of two implicit motor skills, learning of a movement sequence and learning of a visuo-motor mapping. Subjects learned one skill and were tested on that skill 48 h later. Between the learning session and test session, some subjects trained on a second skill. The amount of time between the learning of the two skills varied for different subjects. In both the learning of a movement sequence and the learning of a visuo-motor mapping, we found that remote memories were susceptible to interference, but the passage of time did not afford protection from interference. These results are inconsistent with the long-term consolidation of these motor skills. A possible difference between these tasks and those that do show long-term consolidation is that the present tasks are not dynamic motor skills.     

空间距离对视觉工作记忆巩固的影响

以往研究发现,个体对不同类型的视觉信息进行视觉工作记忆巩固的模式存在差异,如对于方向信息,一次只能有一个项目被巩固进入视觉工作记忆系统,而对于颜色信息,个体则可以一次巩固两个项目进入视觉工作记忆系统。但对于视觉信息的巩固模式是否会受其他因素的影响,目前仍然没有明确的定论。本研究将探讨视觉信息的巩固模式是否可能受到记忆项目空间距离因素的影响。研究采用变化觉察范式、序列-同时呈现操作及控制记忆项目呈现间距的方法,通过3个实验考察记忆项目之间的空间距离是否能够影响个体对颜色信息和方向信息的巩固模式。在三种空间距离水平上序列呈现或同时呈现两个记忆项目,实验结果一致发现记忆项目之间的空间距离会对视觉工作记忆巩固模式产生明显影响,个体在同时呈现条件下的正确率会随着空间距离的增大而降低。这些结果表明对同一类视觉信息进行巩固的过程中所存在的项目数量限制并不是固定的,个体可以采用序列模式或有限容量的并行模式对同一类信息进行巩固,巩固的模式可能与视觉空间注意的分配以及视觉信息所能获得的注意资源有关。     

Sleep directly following learning benefits consolidation of spatial associative memory

The last decade has brought forth convincing evidence for a role of sleep in non-declarative memory. A similar function of sleep in episodic memory is supported by various correlational studies, but direct evidence is limited. Here we show that cued recall of face-location associations is significantly higher following a 12-h retention interval containing sleep than following an equally long period of waking. Furthermore, retention is significantly higher over a 24-h sleep-wake interval than over an equally long wake-sleep interval. This difference occurs because retention during sleep was significantly better when sleep followed learning directly, rather than after a day of waking. These data demonstrate a beneficial effect of sleep on memory that cannot be explained solely as a consequence of reduced interference. Rather, our findings suggest a competitive consolidation process, in which the fate of a memory depends, at least in part, on its relative stability at sleep onset: Strong memories tend to be preserved, while weaker memories erode still further. An important aspect of memory consolidation may thus result from the removal of irrelevant memory "debris."     

The role of partial knowledge in statistical word learning

A critical question about the nature of human learning is whether it is an all-or-none or a gradual, accumulative process. Associative and statistical theories of word learning rely critically on the later assumption: that the process of learning a word’s meaning unfolds over time. That is, learning the correct referent for a word involves the accumulation of partial knowledge across multiple instances. Some theories also make an even stronger claim: Partial knowledge of one word–object mapping can speed up the acquisition of other word–object mappings. We present three experiments that test and verify these claims by exposing learners to two consecutive blocks of cross-situational learning, in which half of the words and objects in the second block were those that participants failed to learn in Block 1. In line with an accumulative account, Re-exposure to these mis-mapped items accelerated the acquisition of both previously experienced mappings and wholly new word–object mappings. But how does partial knowledge of some words speed the acquisition of others? We consider two hypotheses. First, partial knowledge of a word could reduce the amount of information required for it to reach threshold, and the supra-threshold mapping could subsequently aid in the acquisition of new mappings. Alternatively, partial knowledge of a word’s meaning could be useful for disambiguating the meanings of other words even before the threshold of learning is reached. We construct and compare computational models embodying each of these hypotheses and show that the latter provides a better explanation of the empirical data.     

Effects of learning contexts on implicit and explicit learning

Two parallel tasks involving rule learning were identified in Experiment 1A and were used to assess implicit and explicit learning. In both tasks, subjects had to input numbers in order to reach the target values of outputs. The relationship between inputs and outputs was either simple (in the simple task) or complex (in the complex task), and the way in which target values were presented could be in the form of either numbers (in the simple task) or lines (in the complex task). Experiment 1B examined the validity of the explicit measure in the complex task. Experiments 2–4 investigated the interaction between learning contexts and the simple/complex learning tasks. Verbalization and instructions to search for the rules facilitated the simple-task learning and hurt or have no effect on the complex-task learning. In the observational-learning condition, no learning occurred for the simple task, and the complex task learning was impaired. These results suggest that the complex task and simple task involve two distinct learning systems. Other implications are also discussed.     

Sleep dependent consolidation of gross motor sequence learning with motor imagery

Acquisition of gross motor sequence learning with physical and mental training elicits gains in performance. However, the effects of sleep or daytime consolidation after both types of practice remain unclear, especially the effects upon the goal- and movement-based components of a gross motor sequential task. The main purpose of this study was to test the effect of physical practice (PP) and motor imagery practice (MIP) on the acquisition and consolidation processes of gross motor sequence learning.Seventy-six participants were tested before and after PP or MIP on a whole-body sequential paradigm, following either a night of sleep (PP_sleep and MIP_sleep groups) or an equivalent daytime period (PP_day and MIP_day groups). Control groups without training were tested following similar timespans (CTRL_sleep and CTRL_day groups). The number of sequential movements and the centre of mass displacement – corresponding to goal and movement-based components, respectively – were assessed.Results showed that relative to the CTRL groups, the PP and MIP groups improved performance during acquisition. Importantly, only the MIP_sleep group further improved performance after a night of sleep; participants of other groups stabilised their performance after consolidation. Additionally, the number of sequential movements and the centre of mass displacement evolved conjointly without being influenced by the type of training or the nature of the consolidation.To conclude, these results confirm that sleep contributes to the consolidation of gross motor sequence learning acquired with MIP but not PP. The relationship between the goal- and movement-based components of a gross motor sequential task is discussed.