Learning & memory最新文献

Long-term memory (LTM) formation is dependent on neurochemical changes that guarantee that a recently formed memory (short-term memory [STM]) remains in the specific neural circuitry via the consolidation process. The persistence of recognition memory has been evidenced by using behavioral tagging in young adult rats, but it has not been effective on aging. Here, we investigated the effects of treatment with a standardized extract of Ginkgo biloba (EGb) associated with novelty on the consolidation of object location memory (OLM) and its persistence after weak training of spatial object preference in young adult and aged rats. The object location task used in this study included two habituation sessions, training sessions associated or not associated with EGb treatment and contextual novelty, and short-term or long-term retention testing sessions. Altogether, our data showed that treatment with EGb associated with novelty close to the time of encoding resulted in STM that lasted for 1 h and persisted for 24 h for both young adult and aged rats. In aged rats, the cooperative mechanisms induced robust long-term OLM. Our findings support and extend our knowledge about recognition memory in aged rats and the modulating effects of EGb treatment and contextual novelty on the persistence of memory.

Auditory fear conditioning in rats is a widely used method to study learning, memory, and emotional responding. Despite procedural standardizations and optimizations, there is substantial interindividual variability in fear expression during test, notably in terms of fear expressed toward the testing context alone. To better understand which factors could explain this variation between subjects, we here explored whether behavior during training and expression of AMPA receptors (AMPARs) after long-term memory formation in the amygdala could predict freezing during test. We studied outbred male rats and found strong variation in fear generalization to a different context. Hierarchical clustering of these data identified two distinct groups of subjects that independently correlated with a specific pattern of behaviors expressed during initial training (i.e., rearing and freezing). The extent of fear generalization correlated positively with postsynaptic expression of GluA1-containing AMPA receptors in the basolateral nucleus of the amygdala. Our data thus identify candidate behavioral and molecular predictors of fear generalization that may inform our understanding of some anxiety-related disorders, such as posttraumatic stress disorder (PTSD), that are characterized by overgeneralized fear.

The hippocampal formation (HF) facilitates declarative memory, with subfields providing unique contributions to memory performance. Maturational differences across subfields facilitate a shift toward increased memory specificity, with peripuberty sitting at the inflection point. Peripuberty is also a sensitive period in the development of anxiety disorders. We believe HF development during puberty is critical to negative overgeneralization, a common feature of anxiety disorders. To investigate this claim, we examined the relationship between mnemonic generalization and a cross-sectional pubertal maturity index (PMI) derived from partial least squares correlation (PLSC) analyses of subfield volumes and structural connectivity from T1-weighted and diffusion-weighted scans, respectively. Participants aged 9-14 yr, from clinical and community sources, performed a recognition task with emotionally valent (positive, negative, and neutral) images. HF volumetric PMI was positively associated with generalization for negative images. Hippocampal-medial prefrontal cortex connectivity PMI evidenced a behavioral relationship similar to that of the HF volumetric approach. These findings reflect a novel developmentally related balance between generalization behavior supported by the hippocampus and its connections with other regions, with maturational differences in this balance potentially contributing to negative overgeneralization during peripuberty.

A widely accepted view in memory research is that recently stored information can be reactivated during sleep, leading to memory strengthening. Two recent studies have shown that this effect can be reversed in participants with highly disrupted sleep. To test whether weakening of reactivated memories can result directly from sleep disruption, in this experiment we varied the intensity of memory reactivation cues such that some produced sleep arousals. Prior to sleep, participants (local community members) learned the locations of 75 objects, each accompanied by a sound naturally associated with that object. Location recall was tested before and after sleep, and a subset of the sounds was presented during sleep to provoke reactivation of the corresponding locations. Reactivation with sleep arousal weakened memories, unlike the improvement typically found after reactivation without sleep arousal. We conclude that reactivated memories can be selectively weakened during sleep, and that memory reactivation may strengthen or weaken memories depending on additional factors such as concurrent sleep disruption.

Strong evidence has implicated proteasome-mediated protein degradation in the memory consolidation process. However, due to the use of pharmacological approaches, the cell type specificity of this remains unknown. Here, we used neuron-specific and novel astrocyte-specific CRISPR-dCas9-KRAB-MECP2 plasmids to inhibit protein degradation in a cell type-specific manner in the amygdala of male rats. We found that while inhibition of neuronal, but not astrocytic, protein degradation impaired performance during the training session, both resulted in impaired contextual fear memory retention. Together, these data provide the first evidence of a cell type-specific role for protein degradation in the memory consolidation process.

Memory is well known to decline over the course of healthy aging. However, memory is not a monolith and draws from different kinds of representations. Historically, much of our understanding of age-related memory decline stems from recognition of isolated studied items. In contrast, real-life events are often remembered as narratives, and this kind of information is generally missed in typical recognition memory studies. Here, we designed a task to tax mnemonic discrimination of event details, directly contrasting perceptual and narrative memory. Older and younger adults watched an episode of a television show and later completed an old/new recognition test featuring targets, novel foils, and similar lures in narrative and perceptual domains. While we observed no age-related differences on basic recognition of repeated targets and novel foils, older adults showed a deficit in correctly rejecting perceptual, but not narrative, lures. These findings provide insight into the vulnerability of different memory domains in aging and may be useful in characterizing individuals at risk for pathological cognitive decline.

How the dynamic evolution of forgetting changes for different material types is unexplored. By using a common experimental paradigm with stimuli of different types, we were able to directly cross-examine the emerging dynamics and found that even though the presentation sets differ minimally by design, the obtained curves appear to fall on a discrete spectrum. We also show that the resulting curves do not depend on physical time but rather on the number of items shown. All measured curves were compatible with our previously developed mathematical model, hinting to a potential common underlying mechanism of forgetting.

During sleep, recently acquired episodic memories (i.e., autobiographical memories for specific events) are strengthened and transformed, a process termed consolidation. These memories are contextual in nature, with details of specific features interwoven with more general properties such as the time and place of the event. In this study, we hypothesized that the context in which a memory is embedded would guide the process of consolidation during sleep. To test this idea, we used a spatial memory task and considered changes in memory over a 10-h period including either sleep or wake. In both conditions, participants (N = 62) formed stories that contextually bound four objects together and then encoded the on-screen spatial position of all objects. Results showed that the changes in memory over the sleep period were correlated among contextually linked objects, whereas no such effect was identified for the wake group. These results demonstrate that context-binding plays an important role in memory consolidation during sleep.

Sleep consolidates procedural memory for motor skills, and this process is associated with strengthened functional connectivity in hippocampal-striatal-cortical areas. It is unknown whether similar processes occur for procedural memory that requires cognitive strategies needed for problem-solving. It is also unclear whether a full night of sleep is indeed necessary for consolidation to occur, compared with a daytime nap. We examined how resting-state functional connectivity within the hippocampal-striatal-cortical network differs after offline consolidation intervals of sleep, nap, or wake. Resting-state fMRI data were acquired immediately before and after training on a procedural problem-solving task that requires the acquisition of a novel cognitive strategy and immediately prior to the retest period (i.e., following the consolidation interval). ROI to ROI and seed to whole-brain functional connectivity analyses both specifically and consistently demonstrated strengthened hippocampal-prefrontal functional connectivity following a period of sleep versus wake. These results were associated with task-related gains in behavioral performance. Changes in functional communication were also observed between groups using the striatum as a seed. Here, we demonstrate that at the behavioral level, procedural strategies benefit from both a nap and a night of sleep. However, a full night of sleep is associated with enhanced functional communication between regions that support problem-solving skills.

As we age, the added benefit of sleep for memory consolidation is lost. One of the hallmark age-related changes in sleep is the reduction of sleep spindles and slow waves. Gray matter neurodegeneration is related to both age-related changes in sleep and age-related changes in memory, including memory for problem-solving skills. Here, we investigated whether spindles and slow waves might serve as biological markers for neurodegeneration of gray matter and for the related memory consolidation deficits in older adults. Forty healthy young adults (20-35 yr) and 30 healthy older adults (60-85 yr) were assigned to either nap or wake conditions. Participants were trained on the Tower of Hanoi in the morning, followed by either a 90-min nap opportunity or period of wakefulness, and were retested afterward. We found that age-related changes in sleep spindles and slow waves were differentially related to gray matter intensity in young and older adults in brain regions that support sleep-dependent memory consolidation for problem-solving skills. Specifically, we found that spindles were related to gray matter in neocortical areas (e.g., somatosensory and parietal cortex), and slow waves were related to gray matter in the anterior cingulate, hippocampus, and caudate, all areas known to support problem-solving skills. These results suggest that both sleep spindles and slow waves may serve as biological markers of age-related neurodegeneration of gray matter and the associated reduced benefit of sleep for memory consolidation in older adults.