Learning & memory最新文献

Emotional events hold a privileged place in our memories, differing in accuracy and structure from memories for neutral experiences. Although much work has focused on the pronounced differences in memory for negative experiences, there is growing evidence that positive events may lead to more holistic, or integrated, memories. However, it is unclear whether these affect-driven changes in memory structure, which have been found in highly controlled laboratory environments, extend to real-world episodic memories. We ran experiments that assessed memory for experiences created in the laboratory (Experiment 1) and, using smartphones, memories for everyday experiences (Experiment 2). We complement these design innovations with a novel analysis approach to model memory accuracy and integration in both settings. Consistent with past findings, emotional events were subjectively remembered more strongly. These studies also revealed that features of more positive events were indeed more integrated within memory, both in the laboratory and the real world. These effects were specific to participants' emotional responses to the events during encoding rather than general emotional states at the time of retrieval, and reflected a general increase in integration between multiple memory features. Together, these results demonstrate robust differences in memory for positive events, introduce a novel measure of memory integration, and highlight the importance of assessing the impact of emotion on memory beyond the laboratory.

Agency beliefs influence how humans learn from different contexts and outcomes. Research demonstrates that stressors, such as exposure to early-life adversity (ELA), are associated with both agency beliefs and learning, but how these processes interact remains unclear. The current study investigated whether exposure to ELA influences agency and interacts with reinforcement learning in adults. Replicating prior behavioral and computational work, ELA resulted in decreased learning, while increased adversity severity was associated with decreased latent agency beliefs. These findings suggest that exposure to adversity in childhood has a nuanced impact on reinforcement learning and agency beliefs in adulthood.

Social isolation is a risk factor for cognitive impairment. Adolescents may be particularly vulnerable to these effects, because they are in a critical period of development marked by significant physical, hormonal, and social changes. However, it is unclear if the effects of social isolation on learning and memory are similar in both sexes or if they persist into adulthood after a period of recovery. We socially isolated male and female 129Sv/Ev mice throughout adolescence (postnatal days 29-56), provided a 2-week resocialization recovery period, and then tested spatial learning and cognitive flexibility in the active place avoidance task. After behavioral testing, mice were injected with 5'-bromo-2'-deoxyuridine (BrdU) so that lasting effects of social isolation on cell proliferation in the dentate gyrus could be examined. Tissue was also stained for doublecortin (DCX). We found that in males, isolation led to a modest impairment in the rate of initial spatial learning, whereas in females, initial learning was unaffected. However, when the location of the shock zone was switched during the conflict variant of the task, cognitive flexibility was impaired in females only. Similarly, social isolation reduced cell proliferation and the number of immature neurons in the ventral dentate gyrus only in females. Together, these findings indicate that social isolation during adolescence differentially impairs spatial processing in males and females, with effects that persist into adulthood.

Stressful and emotionally arousing experiences induce the release of noradrenergic and glucocorticoid hormones that synergistically strengthen memories but differentially regulate qualitative aspects of memory. This highlights the need for sophisticated behavioral tasks that allow for the assessment of memory quality. The dual-event inhibitory avoidance task for rats is such a behavioral task designed to evaluate both the strength and specificity of memory. The noradrenergic stimulant yohimbine given systemically immediately after the training session was found to enhance both the strength and specificity of memory, whereas the glucocorticoid corticosterone induced a generalized strengthening of memory. As mice are the preferred species for targeted gene and neural circuit manipulations, we here aimed to set up the dual-event inhibitory avoidance task for mice, and to replicate the effects of systemic yohimbine and corticosterone administration on memory strength and specificity. Whereas noninjected control mice efficiently acquired the task and selectively avoided the test context previously associated with footshock, the introduction of posttraining intraperitoneal injections induced testing order effects and substantially increased variability both within groups and across experiments, precluding a thorough investigation of stress hormone effects on memory specificity. Thus, whereas the dual-event inhibitory avoidance task can be used to test the specificity of memory in mice, our findings indicate that intraperitoneal injections impact performance. Therefore, this task is less suitable to assess stress hormone effects on memory specificity in mice.

Chronic stress typically leads to deficits in fear extinction. However, when a delay occurs from the end of chronic stress and the start of fear conditioning (a "recovery"), rats show improved context-cue discrimination, compared to recently stressed rats or nonstressed rats. The infralimbic cortex (IL) is important for fear extinction and undergoes neuronal remodeling after chronic stress ends, which could drive improved context-cue discrimination. Here, glutamatergic IL neurons of Sprague-Dawley male rats were targeted for inhibition using inhibitory designer receptors exclusively activated by designer drugs (DREADDs) and daily injections of clozapine N-oxide (CNO) during a 21-day recovery period from chronic stress. Histological verification confirmed DREADDs in the IL with some spread to nearby medial prefrontal cortex (PFC) regions. CNO administration was then discontinued before fear conditioning started and behavioral testing thereafter so that behavioral assessments occurred without neuronal inhibition. Fear conditioning involved presenting male rats with three tone-foot shock pairings on 1 day, which was followed by 2 days of 15 tone-alone extinction sessions. Daily and repeated inhibition of mainly IL neurons during the 21-day recovery period did not disrupt fear learning or fear extinction in all groups (controls, stressed rats without a recovery, and stressed rats with a recovery). However, chronically stressed rats given a recovery and with DREADD activation showed impaired spontaneous recovery, indicating a failure to form a tone-foot shock association. The findings show that daily inhibition of mainly IL neurons prior to fear conditioning and extinction depends upon the changes that occur during the recovery period following the end of chronic stress.

Early life trauma has been shown to facilitate habitual behavior, which may predispose individuals toward perpetuating maladaptive behaviors. However, previous investigations did not account for other traumatic childhood experiences like racial/ethnic discrimination exposure, nor have they examined the interaction of trauma and habits on real-world adverse outcomes. To examine these effects, we recruited 96 young adults (20.06 ± 1.89 years old) in a study probing early life racial/ethnic discrimination influences on habitual learning, and the conjunctive influences of early life discrimination and habit on disordered eating and substance use. To measure habit responses, participants completed a noise avoidance task during which they responded to abstract stimuli via associated keyboard presses to avoid an aversive screaming sound, after which they performed a devaluation test to measure avoidance habit responses. Participants then completed a series of questionnaires examining early life racial/ethnic discrimination exposure, disordered eating and substance use, and other psychological characteristics. Hierarchical regression results showed that certain early life discrimination subtypes, particularly threat/aggression experienced due to racial/ethnic background, significantly predicted habitual responding above and beyond the effects of psychological confounds. Additionally, overall early life discrimination exposure positively predicted binge eating, but no variables of interest predicted alcohol and drug use. These results expand on extant literature showing the negative impacts of childhood stressors on behavioral control and real-world outcomes.

Stressful events are typically well remembered, but their effects on memory for surrounding neutral events and the underlying mechanisms remain less clear. We hypothesized that stress would enhance memory for events surrounding the stressor, contingent on the memory of the stressor itself. Additionally, we predicted that memory for neutral events would be modulated by pairing them with stressor-related cues. To test these hypotheses, 122 healthy participants encoded a series of images before and after experiencing a stressful or control episode. During encoding, images were preceded by cues from stressor or control contexts. Memory for the stress or control episode and the encoded images was tested 24 h later. Our results showed enhanced memory prioritization, reflected in better memory for central versus peripheral features, for the stressful compared to the control episode. Exposure to the stressful episode further enhanced memory for neutral images preceding the stressor. However, this memory boost occurred only in participants with enhanced memory prioritization for the stressor. Memory for stimuli encoded after the stressor remained unaffected, and there was no evidence for the proposed cueing mechanism. These findings indicate that stressful events enhance memory consolidation only when these events themselves are distinctly represented in memory.

In humans, psychological loss, whether social or nonsocial, can lead to clinical depression, anxiety disorders, and social memory impairments. Researchers have modeled combined social and nonsocial loss in rodents by transitioning them from social, enriched environments (EE) to individual housing, affecting behaviors related to avoidance, stress coping, and cognitive function. However, it remains unclear if these effects are driven by social or nonsocial loss. We examined the effects of nonsocial loss by housing adult male mice in EE before moving them to standard cages, where they were pair-housed, and compared this to mice experiencing complete social loss. Continuous EE reduced social investigation time while leaving social memory intact, also decreasing avoidance behavior. Nonsocial loss restored social investigation and avoidance behavior to control levels, while social loss impaired social memory and increased avoidance. In rodents, social memory and avoidance require ventral hippocampus (vHIP) neuronal oscillations, which involve parvalbumin-positive (PV+) inhibitory interneurons. We found decreased vHIP PV intensity in the social loss group, with no differences in the nonsocial loss group. Most PV+ cells are surrounded by perineuronal nets (PNNs) concentrating GABA_A receptors in their lattice-like holes. Social loss decreased GABA_A-δ expression, a subunit associated with extrasynaptic receptors, across PNN+ soma and in PNN holes, while nonsocial loss reduced gephyrin in these regions. These findings suggest social and nonsocial losses differentially affect vHIP function and behavior, with social loss having a more pronounced impact through mechanisms involving PV+ interneurons, PNN structure, and neurotransmitter receptor expression.

Vagus nerve stimulation (VNS) is a therapeutic intervention previously shown to enhance fear extinction in rats. VNS is approved for use in humans for the treatment of epilepsy, depression, and stroke, and it is currently under investigation as an adjuvant to exposure therapy in the treatment of PTSD. However, the mechanisms by which VNS enhances extinction of conditioned fear remain unresolved. VNS increases norepinephrine levels in extinction-related pathways, but recent studies indicate that norepinephrine release from the locus coeruleus interferes with extinction learning. The purpose of this study is to elucidate the role of the locus coeruleus (LC) in VNS-enhanced fear extinction. Adult male and female tyrosine hydroxylase (Th)-Cre rats were implanted with a stimulating cuff electrode around the left cervical vagus nerve, and a Cre-dependent viral vector expressing the inhibitory opsin ArchT3.0 was infused bilaterally into the LC. Rats then underwent auditory fear conditioning followed by extinction training. During extinction training, rats were divided into four treatment groups: Sham stimulation, Sham with LC inhibition, VNS, and VNS with LC inhibition. Consistent with previous findings, VNS treatment during extinction training significantly reduced freezing 24 h and 2 weeks later. This effect was blocked by optogenetic LC inhibition, suggesting that VNS enhances extinction by engaging the LC.