Positive and negative sources of emotional arousal enhance long-term word-list retention when induced as long as 30 min after learning

The consolidation of newly formed memories occurs slowly, allowing memories to be altered by experience for some time after their formation. Various treatments, including arousal, can modulate memory consolidation when given soon after learning, but the degree of time-dependency of these treatments in humans has not been studied. Thus, 212 participants learned a word list, which was followed by either a positively or negatively valenced arousing video clip (i.e., comedy or surgery, respectively) after delays of 0, 10, 30 or 45 min. Arousal of either valence induced up to 30 min after learning, but not after 45 min, significantly enhanced one-week retrieval. The findings support (1) the time-dependency of memory modulation in humans and (2) other studies that suggest that it is the degree of arousal, rather than valence that modulates memory. Important implications for developing memory intervention strategies and for preserving and validating witness testimony are discussed.     

Infantile amnesia reconsidered: a cross-cultural analysis

A number of theories have been offered over the past hundred years to explain the phenomenon of infantile amnesia, the common inability to remember autobiographical experiences from the first years of life. Recent comparative studies that examine autobiographical memories in different populations, particularly populations in North America and East Asia, have yielded intriguing findings that provide a unique opportunity to revisit some of the major theoretical views and to propose new accounts. In light of these findings, this article discusses five theoretical explanations for infantile amnesia, including cognitive and social discontinuity, the emergence of the self, early parent-child memory sharing, functions of autobiographical memory, and the complexity of life experience. The reconsideration of infantile amnesia from a cross-cultural perspective suggests that while the basic mechanisms and contributing factors may be universal, the specific ways in which these mechanisms and factors are manifested differ qualitatively across cultures. A theoretical approach that takes the larger cultural context into account can help us understand this long-standing puzzle.     

The reciprocal relation between sleep and memory in infancy: Memory‐dependent adjustment of sleep spindles and spindle‐dependent improvement of memories

Sleep spindle activity in infants supports their formation of generalized memories during sleep, indicating that specific sleep processes affect the consolidation of memories early in life. Characteristics of sleep spindles depend on the infant's developmental state and are known to be associated with trait‐like factors such as intelligence. It is, however, largely unknown which state‐like factors affect sleep spindles in infancy. By varying infants’ wake experience in a within‐subject design, here we provide evidence for a learning‐ and memory‐dependent modulation of infant spindle activity. In a lexical‐semantic learning session before a nap, 14‐ to 16‐month‐old infants were exposed to unknown words as labels for exemplars of unknown object categories. In a memory test on the next day, generalization to novel category exemplars was tested. In a nonlearning control session preceding a nap on another day, the same infants heard known words as labels for exemplars of already known categories. Central–parietal fast sleep spindles increased after the encoding of unknown object–word pairings compared to known pairings, evidencing that an infant's spindle activity varies depending on its prior knowledge for newly encoded information. Correlations suggest that enhanced spindle activity was particularly triggered, when similar unknown pairings were not generalized immediately during encoding. The spindle increase triggered by previously not generalized object–word pairings, moreover, boosted the formation of generalized memories for these pairings. Overall, the results provide first evidence for a fine‐tuned regulation of infant sleep quality according to current consolidation requirements, which improves the infant long‐term memory for new experiences.     

Reconsolidation Reconsidered

Some of the considerations that led to a consolidation interpretation of retrograde amnesia (RA), which states that RA results from the disruption of memory processing and storage when neural activity is interrupted by a brain insult, are reviewed here. The time-dependent gradient of memory loss (i.e., new memories are more vulnerable to amnesia than old memories) that characterizes RA seemed to fit nicely with the notion of a cascade of cellular events occurring during the immediate post-acquisition period that would transform a labile representation into a more stable form (i.e., consolidate the memory). However, a variety of observations came to challenge the storage-disruption model, and among these was the finding of amnesia for old but reactivated memories. A recent study by Nader, Schafe, and LeDoux (2000) provides an important analytic extension of the work on "reconsolidation" by showing that inhibition of protein synthesis in the lateral and basal nuclei of the amygdala immediately following the reactivation of old memory will induce retrograde amnesia. We offer a retrieval-oriented conceptualization to account for the temporal gradient and the "reconsolidation" phenomena.     

Amygdala modulation of memory consolidation: interaction with other brain systems

There is a strong consensus that the amygdala is involved in mediating influences of emotional arousal and stress on learning and memory. There is extensive evidence that the basolateral amygdala (BLA) is a critical locus of integration of neuromodulatory influences regulating the consolidation of several forms of memory. Many drug and stress hormone influences converge in activating the release of norepinephrine (NE) within the BLA. Evidence from studies using in vivo microdialysis and high-performance liquid chromatography indicates that increases in amygdala NE levels assessed following inhibitory avoidance training correlate highly with subsequent retention. Other evidence indicates that NE influences on memory consolidation require muscarinic cholinergic activation within the BLA provided by projections from the nucleus basalis magnocellularis (NB). Evidence from several experiments indicates that activation of the BLA plays an essential role in modulating memory consolidation processes involving other brain regions. These findings provide strong support for the hypothesis that the BLA plays a critical role in regulating the consolidation of lasting memories of significant experiences.     

Studies on retrograde and anterograde amnesia of olfactory memory after denervation of the hippocampus by entorhinal cortex lesions

The effect of hippocampal denervation on olfactory memory in rats was tested after interrupting the lateral olfactory tract projections at the level of the entorhinal cortex. When lesioned animals were trained to learn new odors, they showed no evidence of retention 3 h after acquisition. These results confirm earlier data on rapid forgetting in rats after hippocampal deafferentation and are in parallel to the anterograde amnesia typically found in humans with hippocampal damage. On the other hand, preoperatively learned information was minimally impaired after hippocampal deafferentation even if it was acquired within less than 1 h before the lesion. This finding differs from reports on humans as well as monkeys with hippocampal damage where memories formed during a critical time span of months or even years before the lesion are found to be impaired. This may suggest that the consolidation process in humans and rodents has different time scales or that the roles of the human and the rat hippocampal structure in memory formation are somewhat different.     

Reconsolidation reconsidered

Some of the considerations that led to a consolidation interpretation of retrograde amnesia (RA), which states that RA results from the disruption of memory processing and storage when neural activity is interrupted by a brain insult, are reviewed here. The time-dependent gradient of memory loss (i.e., new memories are more vulnerable to amnesia than old memories) that characterizes RA seemed to fit nicely with the notion of a cascade of cellular events occurring during the immediate post-acquisition period that would transform a labile representation into a more stable form (i.e., consolidate the memory). However, a variety of observations came to challenge the storage-disruption model, and among these was the finding of amnesia for old but reactivated memories. A recent study by Nader, Schafe, and LeDoux (2000) provides an important analytic extension of the work on “reconsolidation” by showing that inhibition of protein synthesis in the lateral and basal nuclei of the amygdala immediately following the reactivation of old memory will induce retrograde amnesia. We offer a retrieval-oriented conceptualization to account for the temporal gradient and the “reconsolidation” phenomena.     

情绪唤醒影响记忆巩固过程的神经生理机制

白鼠和人类都对情绪唤醒的经历有更好的记忆。情绪唤醒影响记忆巩固的神经生理机制主要有以下几种方式:(a)情绪唤醒或急性应激,会引发个体内部应激激素的释放,从而增强其记忆巩固过程。(b1)杏仁核的激活对情绪唤醒影响记忆巩固过程十分重要,杏仁核内部去甲肾上腺素(NE)的释放影响记忆巩固过程。(b2)杏仁核投射到负责不同类型记忆加工的脑区,如海马和皮层,从而影响记忆。(c)应激激素影响记忆巩固的过程中,杏仁核内NE的激活在这一过程中扮演着重要角色。综上,情绪唤醒影响记忆巩固的过程,涉及到激素调节、神经调节及二者的共同作用。     

On the role of hippocampal protein synthesis in the consolidation and reconsolidation of object recognition memory

Upon retrieval, consolidated memories are again rendered vulnerable to the action of metabolic blockers, notably protein synthesis inhibitors. This has led to the hypothesis that memories are reconsolidated at the time of retrieval, and that this depends on protein synthesis. Ample evidence indicates that the hippocampus plays a key role both in the consolidation and reconsolidation of different memories. Despite this fact, at present there are no studies about the consequences of hippocampal protein synthesis inhibition in the storage and post-retrieval persistence of object recognition memory. Here we report that infusion of the protein synthesis inhibitor anisomycin in the dorsal CA1 region immediately or 180 min but not 360 min after training impairs consolidation of long-term object recognition memory without affecting short-term memory, exploratory behavior, anxiety state, or hippocampal functionality. When given into CA1 after memory reactivation in the presence of familiar objects, ANI did not affect further retention. However, when administered into CA1 immediately after exposing animals to a novel and a familiar object, ANI impaired memory of both of them. The amnesic effect of ANI was long-lasting, did not happen after exposure to two novel objects, following exploration of the context alone, or in the absence of specific stimuli, suggesting that it was not reversible but was contingent on the reactivation of the consolidated trace in the presence of a salient, behaviorally relevant novel cue. Our results indicate that hippocampal protein synthesis is required during a limited post-training time window for consolidation of object recognition memory and show that the hippocampus is engaged during reconsolidation of this type of memory, maybe accruing new information into the original trace.     

De novo mRNA synthesis is required for both consolidation and reconsolidation of fear memories in the amygdala

Memory consolidation is the process by which newly learned information is stabilized into long-term memory (LTM). Considerable evidence indicates that retrieval of a consolidated memory returns it to a labile state that requires it to be restabilized. Consolidation of new fear memories has been shown to require de novo RNA and protein synthesis in the lateral nucleus of the amygdala (LA). We have previously shown that de novo protein synthesis in the LA is required for reconsolidation of auditory fear memories. One key question is whether protein synthesis during reconsolidation depends on already existing mRNAs or on synthesis of new mRNAs in the amygdala. In the present study, we examined the effect of mRNA synthesis inhibition during consolidation and reconsolidation of auditory fear memories. We first show that intra-LA infusion of two different mRNA inhibitors dose-dependently impairs long-term memory but leaves short-term memory (STM) intact. Next, we show that intra-LA infusion of the same inhibitors dose-dependently blocks post-reactivation long-term memory (PR-LTM), whereas post-reactivation short-term memory (PR-STM) is left intact. Furthermore, the same treatment in the absence of memory reactivation has no effect. Together, these results show that both consolidation and reconsolidation of auditory fear memories require de novo mRNA synthesis and are equally sensitive to disruption of de novo mRNA synthesis in the LA.     

System consolidation of memory during sleep

Over the past two decades, research has accumulated compelling evidence that sleep supports the formation of long-term memory. The standard two-stage memory model that has been originally elaborated for declarative memory assumes that new memories are transiently encoded into a temporary store (represented by the hippocampus in the declarative memory system) before they are gradually transferred into a long-term store (mainly represented by the neocortex), or are forgotten. Based on this model, we propose that sleep, as an offline mode of brain processing, serves the ‘active system consolidation’ of memory, i.e. the process in which newly encoded memory representations become redistributed to other neuron networks serving as long-term store. System consolidation takes place during slow-wave sleep (SWS) rather than rapid eye movement (REM) sleep. The concept of active system consolidation during sleep implicates that (a) memories are reactivated during sleep to be consolidated, (b) the consolidation process during sleep is selective inasmuch as it does not enhance every memory, and (c) memories, when transferred to the long-term store undergo qualitative changes. Experimental evidence for these three central implications is provided: It has been shown that reactivation of memories during SWS plays a causal role for consolidation, that sleep and specifically SWS consolidates preferentially memories with relevance for future plans, and that sleep produces qualitative changes in memory representations such that the extraction of explicit and conscious knowledge from implicitly learned materials is facilitated.     

Retrieval failure versus memory loss in experimental amnesia: definitions and processes

For at least 40 years, there has been a recurring argument concerning the nature of experimental amnesia, with one side arguing that amnesic treatments interfere with the formation of enduring memories and the other side arguing that these treatments interfere with the expression of memories that were effectively encoded. The argument appears to stem from a combination of (1) unclear definitions and (2) real differences in the theoretical vantages that underlie the interpretation of relevant data. Here we speak to how the field might avoid arguments that are definitional in nature and how various hypotheses fare in light of published data. Existing but often overlooked data favor very rapid (milliseconds) synaptic consolidation, with experimental amnesia reflecting, at least in part, deficits in retrieval rather than in the initial storage of information.     

Networks of neurons, networks of genes: an integrated view of memory consolidation

Investigations into the mechanisms of memory formation have abided by the central tenet of the consolidation theory-that memory formation occurs in stages which differ in their requirement for protein synthesis. The current most widely accepted hypothesis posits that new memories are encoded as neural activity-induced changes in synaptic efficacy, and stabilization of these changes requires de novo protein synthesis. However, the basic assumptions of this view have been challenged by concerns regarding the specificity of the effects of the protein synthesis inhibitors used to support the claim. Studies on immediate-early genes (IEGs), in particular Arc, provide a distinct and independent perspective on the issue of the requirement of new protein synthesis in synaptic plasticity and memory consolidation. The IEG Arc and its protein are dynamically induced in response to neuronal activity, and are directly involved in synaptic plasticity and memory consolidation. Although we provide extensive data on Arc's properties to address the requirement of genomic and proteomic responses in memory formation, Arc is merely one element in a network of genes that interact in a coordinated fashion to serve memory consolidation. From gene expression and other studies, we propose the view that the stabilization of a memory trace is a continuous and ongoing process, which does not have a discrete endpoint and cannot be reduced to a single deterministic "molecular cascade". Rather, memory traces are maintained within metastable networks, which must integrate and update past traces with new ones. Such an updating process may well recruit and use many of the plasticity mechanisms necessary for the initial encoding of memory.     

Fading in

Patient H.M. can form new memories and maintain them for a few seconds before they fade away. From a neurobiological perspective, this amnesia is usually attributed to the absence of memory consolidation, that is, memory storage. An alternative view holds that this impairment reflects that the memory is present but cannot be retrieved. This debate has been unresolved for decades. Here, we will consider some of the arguments that make it so difficult to resolve this issue. In addition, some recent work will be discussed that has gone beyond the shortcomings of previous experimental approaches to strongly suggest that amnesia can be due to a retrieval impairment that can be overcome with a reminder--an example of memories fading in. Finally, this review will suggest some strategies for resolving this debate.     

The temporal dynamics of consolidation and reconsolidation decrease during postnatal development

The temporal dynamics of consolidation and reconsolidation of taste/odor aversion memory are evaluated during rat pup growth at postnatal days 3, 10, and 18. This is assessed through the temporal gradients of efficacy of a protein synthesis inhibitor (anisomycin) in inducing amnesia after either acquisition (consolidation) or reactivation (reconsolidation). The results show a progressive reduction with age of the delay during which the inhibitor is able to induce amnesia. Control experiments rule out a reduction of anisomycin efficacy due to blood brain barrier growth or decrease in protein synthesis inhibition. Thus, these results present the first evidence that the protein synthesis-dependent phase of memory stabilization requires less time with age. This decrease occurs in parallel for consolidation and reconsolidation. Such changes in the dynamics of memory processing could contribute to the cognitive improvement associated with development.     

Muscarinic cholinergic influences in memory consolidation

The central cholinergic system and muscarinic cholinergic receptor (mR) activation have long been associated with cognitive function. Although mR activation is no doubt involved in many aspects of cognitive functioning, the extensive evidence that memory is influenced by cholinergic treatments given after training either systemically or intra-cranially clearly indicates that cholinergic activation via mRs is a critical component in modulation of memory consolidation. Furthermore, the evidence indicates that activation of mRs in the basolateral amygdala (BLA) plays an essential role in enabling other neuromodulatory influences on memory consolidation. Memory can also be affected by posttraining activation of mRs in the hippocampus, striatum and cortex. Evidence of increases in hippocampal and cortical acetylcholine (ACh) levels following learning experiences support the view that endogenous ACh release is involved in long-term memory consolidation. Furthermore, the findings indicating that mR drug treatments influence plasticity in the hippocampus and in sensory cortices strongly suggest that mR activation is involved in the storage of information in these brain regions.     

行为干预情绪记忆再巩固：从实验室到临床转化

重新激活已经储存的记忆会重返暂时不稳定的状态, 需要经历重新稳定, 称为记忆再巩固。在这期间可以通过多种行为手段破坏、强化或更新原始记忆痕迹, 这为开发一种革命性的情绪记忆障碍治疗方法开辟了道路。然而, 即使在简单的实验模型中引发记忆再巩固的条件也是复杂的, 这给临床转化带来了困难与挑战。未来研究可以设置更具生态效应的基础模型, 寻求引发以及干预再巩固的最佳方式, 从神经生理、细胞分子层面进一步深化其内在机理研究。     

Fragment memories mark the end of childhood amnesia

Adults described and dated two kinds of first remembrances: a personal event memory (the recollection of a personal episode that had occurred at some time in some place) and a memory fragment (an isolated memory moment having no event context and remembered, perhaps, as an image, a behavior, or an emotion). First fragment memories were judged to have originated substantially earlier in life than first event memories--approximately 3 1/3 years of age for first fragment memories versus roughly 4 years of age for first event memories. We conclude that the end of childhood amnesia is marked not by our earliest episodic memories, but by the earliest remembered fragments of childhood experiences.     

Islands of memory: Autobiographical remembering in amnestics

In amnestics with anterograde amnesia, memories of post-onset autobiographical experiences, if present at all, are typically barren and impoverished. However, there have been sporadic reports of islands of memory—memories that are vivid, detailed, and specific to time and place. The aim of this study was to verify the presence of such memories and examine their incidence rate. Anterograde amnestics were interviewed in their home using a narrative interviewing strategy with a view to describing memory in everyday life. Each autobiographical memory of a post-onset event was coded for quantity-length, and quality-episodicity. In just over half of the amnestics (8 out of 14), a memory that was lengthy, rich in personal details, and localisable was recollected. The quantitative and qualitative aspects of these island memories were significantly different from the other autobiographical memories that the amnestics supplied. These memories were at odds with what would be expected on the basis of their performance on standardised memory instruments. Our findings suggest there is occasionally more variability in remembering of autobiographical experiences in some amnestics than has traditionally been believed.