Durable Memories Research Articles

Parallel Engagement of Regions Associated with Encoding and Later Retrieval Forms Durable Memories.

The fate of a memory is partly determined at initial encoding. However, the behavioral consequences of memory formation are often tested only once and shortly after learning, which leaves the neuronal predictors for the formation of durable memories largely unknown. Here, we hypothesized that durable memory formation (as opposed to weak or no memory formation) is reflected through increased activation in the medial temporal lobes and prefrontal cortex, and more consistent processing (i.e., stronger pattern similarity) across encoding material. Thirty-four human subjects studied unique picture-location associations while undergoing fMRI and performed a cued recall test immediately after study as well as 48 h later. Associative memories were defined as "weak" if they were retrieved during the immediate test only. Conversely, "durable" memories persisted also after 48 h. The posterior cingulate cortex showed increased pattern similarity during successful memory formation, independent of the eventual durability. For durable memory encoding, we found increased activation in medial and inferior temporal, prefrontal, and parietal regions. This was accompanied by stronger pattern similarity in lateral prefrontal and parietal regions, as well as in anterior and posterior midline structures that were also engaged during later memory retrieval. Thus, we show that pattern similarity, or consistent processing, in the posterior cingulate cortex predicts associative memory formation at encoding. If this is paralleled by additional activation increases in regions typically related to encoding, and by consistent processing in regions involved in later retrieval, formed memories appear durable for at least 48 h. Successful memory formation is typically associated with increased neuronal activation in medial temporal and prefrontal regions at encoding, but memory is often assessed only once and shortly after study. Here, we addressed memory durability, and investigated the neuronal underpinnings of encoding for associations remembered over a longer period of time, less long, or immediately forgotten. We showed that durable memory formation is dependent on increased activation in the hippocampus and neocortical regions related to encoding, and on consistent processing of associative memory traces in midline structures that are involved in later memory retrieval. These findings highlight how durable memories are formed.

Decoupling of large-scale brain networks supports the consolidation of durable episodic memories

At a large scale, the human brain is organized into modules of interconnected regions, some of which play opposing roles in supporting cognition. In particular, the Default-Mode Network (DMN) has been linked to operations on internal representations, while task-positive networks are recruited during interactions with the external world. Here, we test the hypothesis that the generation of durable long-term memories depends on optimal recruitment of such antagonistic large-scale networks. As long-term memory consolidation is a process ongoing for days and weeks after an experience, we propose that individuals characterized by strong decoupling of the DMN and task-positive networks at rest operate in a mode beneficial for the long-term stabilization of episodic memories. To capture network connectivity unaffected by transient task demands and representative of brain behavior outside an experimental setting, 87 participants were scanned during rest before performing an associative encoding task. To link individual resting-state functional connectivity patterns to time-dependent memory consolidation processes, participants were given an unannounced memory test, either after a brief interval or after a retention period of ~6 weeks. We found that participants with a resting state characterized by high synchronicity in a DMN-centered network system and low synchronicity between task-positive networks showed superior recollection weeks after encoding. These relationships were not observed for information probed only hours after encoding. Furthermore, the two network systems were found to be anticorrelated. Our results suggest that this memory-relevant antagonism between DMN and task-positive networks is maintained through complex regulatory interactions between the systems.

Mechanisms underlying encoding of short-lived versus durable episodic memories.

We continuously encounter and process novel events in the surrounding world, but only some episodes will leave detailed memory traces that can be recollected after weeks and months. Here, our aim was to monitor brain activity during encoding of events that eventually transforms into long-term stable memories. Previous functional magnetic resonance imaging (fMRI) studies have shown that the degree of activation of different brain regions during encoding is predictive of later recollection success. However, most of these studies tested participants' memories the same day as encoding occurred, whereas several lines of research suggest that extended post-encoding processing is of crucial importance for long-term consolidation. Using fMRI, we tested whether the same encoding mechanisms are predictive of recollection success after hours as after a retention interval of several weeks. Seventy-eight participants were scanned during an associative encoding task and given a source memory test the same day or after ∼6 weeks. We found a strong link between regional activity levels during encoding and recollection success over short time intervals. However, results further showed that durable source memories, i.e., events recollected after several weeks, were not simply the events associated with the highest activity levels at encoding. Rather, strong levels of connectivity between the right hippocampus and perceptual areas, as well as with parts of the self-referential default-mode network, seemed instrumental in establishing durable source memories. Thus, we argue that an initial intensity-based encoding is necessary for short-term encoding of events, whereas additional processes involving hippocampal-cortical communication aid transformation into stable long-term memories.

'Memory and molecular turnover,' 30years after inception.

In 1984 Sir Francis Crick hypothesized that memory is recorded in the brain as reversible modifications to DNA and protein, but acknowledged that most biomolecules turn over too rapidly to account for long-term memories. To accommodate this possible paradox he modeled an enzymatic mechanism to maintain modifications on hemi-modified multimeric symmetrical molecules. While studies on the turnover of chromatin modifications that may be involved in memory are in their infancy, an exploration of his model in the light of modern epigenetics produced somewhat surprising results. The molecular turnover rates for two classes of chromatin modifications believed to record and store durable memories were approximated from experiments using diverse approaches and were found to be remarkably short. The half-lives of DNA cytosine methylation and post-translationally modified nucleosomal histones are measured in hours and minutes, respectively, for a subset of sites on chromatin controlling gene expression. It appears likely that the turnover of DNA methylation in the brain and in neurons, in particular, is even more rapid than in other cell types and organs, perhaps accommodating neuronal plasticity, learning, and memory. The machinery responsible for the rapid turnover of DNA methylation and nucleosomal histone modifications is highly complex, partially redundant, and appears to act in a sequence specific manner. Molecular symmetry plays an important part in maintaining site-specific turnover, but its particular role in memory maintenance is unknown. Elucidating Crick’s paradox, the contradiction between rapid molecular turnover of modified biomolecules and long-term memory storage, appears fundamental to understanding cognitive function and neurodegenerative disease.

Multibit Data Storage States Formed in Plasma-Treated MoS2 Transistors

New multibit memory devices are desirable for improving data storage density and computing speed. Here, we report that multilayer MoS2 transistors, when treated with plasmas, can dramatically serve as low-cost, nonvolatile, highly durable memories with binary and multibit data storage capability. We have demonstrated binary and 2-bit/transistor (or 4-level) data states suitable for year-scale data storage applications as well as 3-bit/transistor (or 8-level) data states for day-scale data storage. This multibit memory capability is hypothesized to be attributed to plasma-induced doping and ripple of the top MoS2 layers in a transistor, which could form an ambipolar charge-trapping layer interfacing the underlying MoS2 channel. This structure could enable the nonvolatile retention of charged carriers as well as the reversible modulation of polarity and amount of the trapped charge, ultimately resulting in multilevel data states in memory transistors. Our Kelvin force microscopy results strongly support this hypothesis. In addition, our research suggests that the programming speed of such memories can be improved by using nanoscale-area plasma treatment. We anticipate that this work would provide important scientific insights for leveraging the unique structural property of atomically layered two-dimensional materials in nanoelectronic applications.

A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid-induced spatial memory improvements in young rats

The increase in incidence and prevalence of neurodegenerative diseases highlights the need for a more comprehensive understanding of how food components may affect neural systems. In particular, flavonoids have been recognized as promising agents capable of influencing different aspects of synaptic plasticity resulting in improvements in memory and learning in both animals and humans. Our previous studies highlight the efficacy of flavonoids in reversing memory impairments in aged rats, yet little is known about the effects of these compounds in healthy animals, particularly with respect to the molecular mechanisms by which flavonoids might alter the underlying synaptic modifications responsible for behavioral changes. We demonstrate that a 3-week intervention with two dietary doses of flavonoids (Dose I: 8.7 mg/day and Dose II: 17.4 mg/day) facilitates spatial memory acquisition and consolidation (24 recall) (p < 0.05) in young healthy rats. We show for the first time that these behavioral improvements are linked to increased levels in the polysialylated form of the neural adhesion molecule (PSA-NCAM) in the dentate gyrus (DG) of the hippocampus, which is known to be required for the establishment of durable memories. We observed parallel increases in hippocampal NMDA receptors containing the NR2B subunit for both 8.7 mg/day (p < 0.05) and 17.4 mg/day (p < 0.001) doses, suggesting an enhancement of glutamate signaling following flavonoid intervention. This is further strengthened by the simultaneous modulation of hippocampal ERK/CREB/BDNF signaling and the activation of the Akt/mTOR/Arc pathway, which are crucial in inducing changes in the strength of hippocampal synaptic connections that underlie learning. Collectively, the present data supports a new role for PSA-NCAM and NMDA-NR2B receptor on flavonoid-induced improvements in learning and memory, contributing further to the growing body of evidence suggesting beneficial effects of flavonoids in cognition and brain health.

Spatial behavior and seizure-induced changes in c-fos mRNA expression in young and old rats

The subcellular processes of gene induction and expression in the hippocampus are likely to underlie some of the known age-related impairments in spatial learning and memory. It is well established that immediate-early genes are rapidly and transiently induced in response to neuronal activity and this expression is required for stabilization of durable memories. To examine whether age-related memory impairment might be caused, in part, by differences in the level of cellular activation or subcellular processing, c-fos expression in CA1 pyramidal and dentate gyrus granule cells in the dorsal hippocampus of young and old rats was determined using fluorescence in situ hybridization and reverse transcription polymerase chain reaction. No significant age differences were found in the numbers of pyramidal or granule cells that show c-fos expression; however, c-fos mRNA transcripts were altered in these 2 cell types in aged animals. These findings suggest that though the networks of cells that participate in behavior or seizure-induced activity are largely maintained in aged rats, their RNA transcript levels are altered. This might, in part, contribute to cognitive deficits frequently observed with advancing age.

Capacity-Enhancing Synaptic Learning Rules in a Medial Temporal Lobe Online Learning Model

Medial temporal lobe structures are responsible for recording the continuous stream of autobiographical memories that define our unique personal history. Remarkably, these areas can construct durable memories from brief exposures to the constantly changing activity patterns arriving from antecedent cortical areas. Using a computer model of the hippocampal Schaffer collateral pathway that incorporates evidence for dendritic spikes in CA1 pyramidal neurons, we searched for biologically-plausible long-term potentiation (LTP) and homeostatic depression (HD) rules that maximize "online" learning capacity. We found memory utilization is most efficient when (1) very few synapses are modified to store each pattern, (2) LTP, the learning operation, is dendrite-specific and gated by distinct pre- and postsynaptic thresholds, (3) HD, the forgetting operation, co-occurs with LTP and targets least-recently potentiated synapses, and (4) both LTP and HD are all-or-none, leading de facto to binary-valued synaptic weights. In networks containing up to 40 million synapses, the learning scheme led to order-of-magnitude capacity increases compared to conventional plasticity rules.

Memories for emotional autobiographical events following unilateral damage to medial temporal lobe

Abnormalities of both memory and emotion have been reported in patients with unilateral damage to the anteromedial temporal lobe, probably reflecting the functions of the amygdala and hippocampus in these processes. Emotion and memory are also known to interact: emotional experiences often leave remarkably durable autobiographical memories. To explore this interaction, and to extend prior studies to the domain of autobiographical memory, we investigated the recollection of real-life emotional events in patients with unilateral damage to the anteromedial temporal lobe. Twenty-three patients who had undergone unilateral temporal lobectomy for the treatment of epilepsy (12 left, 11 right) and 20 healthy comparison participants completed an emotional autobiographical memory test. Participants were asked to recollect their five most emotional memories from any time in their lives and then they completed a word-cued autobiographical memory task. Participants dated each memory and gave ratings on scales of pleasantness, intensity, significance, novelty, vividness and frequency of rehearsal. Left temporal lobectomy (LTL) and healthy comparison groups generated similar numbers of pleasant and unpleasant memories, whereas the right temporal lobectomy (RTL) group produced significantly fewer memories of unpleasant events (P < 0.01). When memories were further categorized according to pleasantness and intensity, the RTL group produced significantly fewer unpleasant/high intensity memories than the other groups (P < 0.01). All groups reported more memories from between the ages of 10 and 30 (the so-called autobiographical memory 'bump'). The results demonstrate a positive bias in the recollection of autobiographical memory following right-sided anteromedial temporal damage. This finding is consistent with the notion that the right, but not the left, anteromedial temporal lobe is involved in the retrieval of negatively valenced, high-intensity memories.

Neural Correlates of Successful and Unsuccessful Verbal Memory Encoding

Recent neuroimaging studies suggest that episodic memory encoding involves a network of neocortical structures which may act interdependently with medial temporal lobe (mTL) structures to promote the formation of durable memories, and that activation in certain structures is modulated according to task performance. Functional magnetic resonance imaging (fMRI) was used to determine the neural structures recruited during a verbal episodic encoding task and to examine the relationship between activation during encoding and subsequent recognition memory performance across subjects. Our results show performance-correlated activation during encoding both in neocortical and medial temporal structures. Neocortical activations associated with later successful and unsuccessful recognition memory were found to differ not only in magnitude, but also in hemispheric laterality. These performance-related hemispheric effects, which have not been previously reported, may correspond to between-subject differences in encoding strategy.

Remodeling of Synaptic Actin Induced by Photoconductive Stimulation

Use-dependent synapse remodeling is thought to provide a cellular mechanism for encoding durable memories, yet whether activity triggers an actual structural change has remained controversial. We use photoconductive stimulation to demonstrate activity-dependent morphological synaptic plasticity by video imaging of GFP-actin at individual synapses. A single tetanus transiently moves presynaptic actin toward and postsynaptic actin away from the synaptic junction. Repetitive spaced tetani induce glutamate receptor-dependent stable restructuring of synapses. Presynaptic actin redistributes and forms new puncta that label for an active synapse marker FM5-95 within 2 hr. Postsynaptic actin sprouts projections toward the new presynaptic actin puncta, resembling the axon-dendrite interaction during synaptogenesis. Our results indicate that activity-dependent presynaptic structural plasticity facilitates the formation of new active presynaptic terminals.

Dissociative detachment and memory impairment: Reversible amnesia or encoding failure?

The authors propose that clinicians endeavor to differentiate between reversible and irreversible memory failures in patients with dissociative symptoms who report “memory gaps” and “lost time”. The classic dissociative disorders, such as dissociative amnesia and dissociative identity disorder, entail reversible memory failures associated with encoding experience in altered states. The authors propose another realm of memory failures associated with severe dissociative detachment that may preclude the level of encoding of ongoing experience needed to support durable autobiographical memories. They describe how dissociative detachment may be intertwined with neurobiological factors that impair memory, and they spell out the significance of distinguishing reversible and irreversible memory impairment for diagnosis, patient education, psychotherapy, and research.

Is Posttraumatic Stress Disorder an Overlearned Survival Response? An Evolutionary-Learning Hypothesis

Contemporary learning theories of posttraumatic stress disorder (PTSD) provide an explanation for the phobic avoidant features but do not account fully for the intrusive phenomena that are so characteristic of the disorder. This article hypothesizes that a primitive learning center in the limbic system rehearses traumatic memories immediately following exposure to trauma, thus inducing durable memories of the sources of novel threat. It is postulated that the mechanism developed during early evolution when, in the absence of cognitive mechanisms, automatic learning following single exposure to novel threat would have conferred survival value on the species. With evolution of the brain, a second cortical pathway developed for the cognitive processing of trauma memories. It is possible that synchrony between the two phylogentically distinct pathways may be lost in vulnerable individuals under conditions of extreme stress resulting in failure of cortical inhibition of limbic trauma rehearsal mechanisms. A mismatch between archaic biological mechanisms and novel cues in the modern environment also may play a role in triggering traumatic memories and associated fight and flight reactions. The intrusive phenomena of PTSD thus may reflect an "overlearned survival response" in those in whom the putative limbic rehearsal mechanism evades cortical control. The heuristic value and limitations of such an evolutionary-learning theory are discussed.

Durable write-once optical disk memories for 800nmusing silver island films

Durable write-once (WO) optical disk media have been demonstrated by using silver island films with a protection layer of fluorine-contained polymers. The reflectance of the silver island films is high at the wavelength of 800 nm and can be greatly lowered by laser irradiation, owing to the thermal deformation of the islands. Laser writing has been experimentally confirmed at almost the same line speed as that of compact discs (CDs). Therefore it is expected that a CD-compatible write-once optical disc can be realised.

Strength of scopolamine-induced amnesia as a function of time between training and testing

Variations in the strength of scopolamine-induced amnesia as a function of age of the habit were studied in Swiss Webster mice. Animals were trained in an active avoidance task to a criterion of 9/10 avoidances and immediately following training injected with scopolamine hydrochloride (1.0 mg/kg) or saline. Retention of the avoidance learning was evaluated by testing different groups of animals 1, 3, 7, 10, 14, and 28 days following training. The retention test consisted of five trials in which the CS but not the UCS was presented. Results indicated that saline-treated mice exhibited near-perfect retention up to 14 days post-training with forgetting beginning to be apparent at 28 days. Scopolamine treatment produced strong amnesia in animals tested 1 and 3 days post-training but normal retention in animals tested 7 and 10 days after learning. The amnesia abruptly reappeared at 14 days after which time it remained stable. The marked similarity of the scopolamine retention curve to changes in the strength of memory of discrimination learning in undertrained rats reported by Deutsch suggested that scopolamine resulted in the storage of a weak memory of the avoidance response. To explore this idea further we trained mice to a criterion (4/5) which would result in a weak avoidance response and tested different groups 1, 3, 10, 14, and 28 days following learning. Results showed that strength of the memory of avoidance learning increased up to 10 days and then decreased abruptly at 14 days thus replicating the general shape of the retention curve produced by injecting scopolamine following strong training. These data suggest that scopolamine disrupts processes essential for the formation of durable memories.