Neurobiology of Learning and Memory最新文献

Reinstating the context present at encoding during the test phase generally enhances recognition memory compared with changing the context when specific item–context associations are established during encoding. However, it remains unclear whether context reinstatement improves the performance in differentiating between old and similar items in recognition memory tests and what underlying cognitive processes are involved. Using the context reinstatement paradigm together with event-related potentials (ERP), we examined the context-dependent effects of background scenes on recognition discrimination among similar objects. Participants were instructed to associate intentionally specific objects with background scenes during the encoding phase and subsequently complete an object recognition memory task, during which old and similar new objects were presented superimposed over the studied old or similar new background scenes. Electroencephalogram was recorded to measure the electrophysiological manifestations of cognitive processes associated with episodic retrieval. Behavioral results revealed enhanced performance in differentiating old from similar objects in the old context, as opposed to the similar context condition. Importantly, ERP results indicated a more pronounced recollection-related parietal object old/new effect in the old context compared to the similar context condition. This suggests that the ability to distinguish between old and similar objects in recognition memory is primarily driven by recollection rather than familiarity, particularly when the encoding context is reinstated during the test phase. Our findings are in line with the account that the impact of context reinstatement on object recognition memory is attributable to the enhanced recollection of specific item–context associations during retrieval and provides evidence for the specificity of episodic associative representations.

The reminder of a previously-learned memory can render that memory vulnerable to disruption or change in expression. Such memory alterations have been viewed as supportive of the framework of memory reconsolidation. However, alternative interpretations and inconsistencies in the replication of fundamental findings have raised questions particularly in the domain of human declarative memory. Here we present a series of related experiments, all of which involve the learning of a declarative memory, followed 1–2 days later by memory reminder. Post-reminder learning of interfering material did result in modulation of subsequent recall at test, but the precise manifestation of that interference effect differed across experiments. With post-reminder performance of a visuospatial task, a quantitative impairment in test recall performance was observed within a visual list-learning paradigm, but not in a foreign vocabulary learning paradigm. These results support the existence of reminder-induced memory processes that can lead to the alteration of subsequent memory performance by interfering tasks. However, it remains unclear whether these effects are reflective of modulation or impairment of the putative memory reconsolidation process.

Remembering an unfamiliar person and the contextual conditions of that encounter is important for adaptive future behavior, especially in a potentially dangerous situation. Initiating defensive behavior in the presence of former dangerous circumstances can be crucial. Recent studies showed selective electrocortical processing of faces that were previously seen in a threat context compared to a safety context, however, this was not reflected in conscious recognition performance. Here, we investigated whether previously seen threat-faces, that could not be remembered, were capable to activate defensive psychophysiological response systems. During an encoding phase, 50 participants with low to moderate levels of anxiety viewed 40 face pictures with neutral expressions (6 s each), without an explicit learning instruction (incidental learning task). Each half of the faces were presented with contextual background colors that signaled either threat-of-shock or safety. In the recognition phase, all old and additional new faces (total of 60) were presented intermixed without context information. Participants had to decide whether a face was new or had been presented previously in a threatening or a safe context. Results show moderate face recognition independent of context conditions. Startle reflex and skin conductance responses (SCR) were more pronounced for threat compared to safety during encoding. For SCR, this differentiation was enhanced with higher levels of depression and anxiety. There were no differential startle reflex or SCR effects during recognition. From a clinical perspective, these findings do not support the notion that perceptual biases and physiological arousal directly relate to threat-associated identity recognition deficits in healthy and clinical participants with anxiety and trauma-related disorders.

In the present studies, we assessed the effect of the 5-HT_1A receptor (R) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on motor and exploratory behaviors, object and place recognition and dopamine transporter (DAT) and serotonin transporter (SERT) binding in the rat brain. In Experiment I, motor/exploratory behaviors were assessed in an open field after injection of either 8-OH-DPAT (0.1 and 3 mg/kg) or vehicle for 30 min without previous habituation to the open field. In Experiment II, rats underwent a 5-min exploration trial in an open field with two identical objects. After injection of either 8-OH-DPAT (0.1 and 3 mg/kg) or vehicle, rats underwent a 5-min test trial with one of the objects replaced by a novel one and the other object transferred to a novel place. Subsequently, N-o-fluoropropyl-2b-carbomethoxy-3b-(4-[¹²³I]iodophenyl)-nortropane ([¹²³I]FP-CIT; 11 ± 4 MBq) was injected into the tail vein. Regional radioactivity accumulations were determined post mortem with a well counter. In both experiments, 8-OH-DPAT dose-dependently increased ambulation and exploratory head-shoulder motility, whereas rearing was dose-dependently decreased. In the test rial of Experiment II, there were no effects of 8-OH-DPAT on overall activity, sitting and grooming. 8-OH-DPAT dose-dependently impaired recognition of object and place. 8-OH-DPAT (3 mg/kg) increased DAT binding in the dorsal striatum relative to both vehicle and 0.1 mg/kg 8-OH-DPAT. Furthermore, in the ventral striatum, DAT binding was decreased after 3 mg/kg 8-OH-DPAT relative to vehicle. Findings indicate that motor/exploratory behaviors, memory for object and place and regional dopamine function may be modulated by the 5-HT_1AR. Since, after 8-OH-DPAT, rats exhibited more horizontal and less (exploratory) vertical motor activity, while overall activity was not different between groups, it may be inferred, that the observed impairment of object recognition was not related to a decrease of motor activity as such, but to a decrease of intrinsic motivation, attention and/or awareness, which are relevant accessories of learning. Furthermore, the present findings on 8-OH-DPAT action indicate associations not only between motor/exploratory behavior and the recognition of object and place but also between the respective parameters and the levels of available DA in dorsal and ventral striatum.

The effects of acute stress on memory encoding are complex, and we do not yet know all of the conditions that can determine whether stress at encoding improves or impairs memory. Recent work has found that changing contexts between encoding and stress can abolish the effects of post-encoding stress on memory, suggesting that context may play an important role in the effects of stress on memory. However, the role of context in the effects of stress on memory encoding is not yet known. We addressed this gap by examining the effects of context on the influence of acute stress on memory encoding. In a 2 × 2 experimental design, participants (N = 103) completed either a stressor (i.e., Socially Evaluated Cold Presser Test) or control task (i.e., warm water control) before completing a memory encoding task, which occurred in either in the same room as or a different room from the stressor or control task. Memory retrieval was tested for each participant within the context that they completed the encoding task. We found that, relative to nonstressed (i.e., control) participants, stressed participants who switched contexts prior to encoding showed better memory for both negative and neutral images. In contrast, when the stressor or control task occurred in the same room as memory encoding, stress had no beneficial effect on memory. These results highlight the importance of the ongoing context as a determinant of the effects of stress on memory encoding and present a challenge to current theoretical accounts of stress and memory.

A single bout of cardiovascular exercise (CE) performed after practice can facilitate the consolidation of motor memory. However, the effect is variable and may be modulated by different factors such as the motor task’s or participant’s characteristics and level of awareness during encoding (implicit vs explicit learning). This study examines the effects of acute CE on the consolidation of motor sequences learned explicitly and implicitly, exploring the potential moderating effect of fitness level and awareness. Fifty-six healthy adults (24.1 ± 3.3 years, 32 female) were recruited. After practicing with either the implicit or explicit variant of the Serial Reaction Time Task (SRTT), participants either performed a bout of 16 min of vigorous CE or rested for the same amount of time. Consolidation was quantified as the change in SRTT performance from the end of practice to a 24 h retention test. Fitness level (V̇O_2peak) was determined through a graded exercise test. Awareness (implicit vs explicit learning) was operationalized using a free recall test conducted immediately after retention. Our primary analysis indicated that CE had no statistically significant effects on consolidation, regardless of the SRTT’s variant utilized during practice. However, an exploratory analysis, classifying participants based on the level of awareness gained during motor practice, showed that CE negatively influenced consolidation in unfit participants who explicitly acquired the motor sequence. Our findings indicate that fitness level and awareness in sequence acquisition can modulate the interaction between CE and motor memory consolidation. These factors should be taken into account when assessing the effects of CE on motor memory.

Conditioned responding gradually stops during successful extinction learning. The renewal effect is defined as the recovery of a extinguished conditioned response when the context of extinction is different from acquisition. The stress hormone cortisol is known to have an influence on extinction memory and associative learning. Different effects of cortisol on behaviour and brain activity have been observed with respect to stress timing, duration, and intensity. However, the influence of cortisol prior to the initial encoding of stimulus-outcome associations on extinction learning, renewal and its behavioural and neurobiological correlates is still largely unknown. In our study, 60 human participants received 20 mg cortisol or placebo and then learned, extinguished, and recalled the associations between food stimuli presented in distinct contexts and different outcomes in three subsequent task phases. Learning performance during acquisition and extinction phases was equally good for both treatment groups. In the cortisol group, significantly more participants showed renewal compared to placebo. In the subgroup of participants with renewal, cortisol treated participants showed significantly better extinction learning performance compared to placebo. Participants showing renewal had in general difficulties with recalling extinction memory, but in contrast to placebo, the cortisol group exhibited a context-dependent impairment of extinction memory recall. Imaging analyses revealed that cortisol decreased activation in the hippocampus during acquisition. The cortisol group also showed reduced dorsolateral prefrontal cortex activation when extinction learning took place in a different context, but enhanced activation in inferior frontal gyrus during extinction learning without context change. During recall, cortisol decreased ventromedial prefrontal cortex activation. Taken together, our findings illustrate cortisol as a potent modulator of extinction learning and recall of extinction memory which also promotes renewal.

The amygdala and prefrontal cortex (PFC) undergo dramatic changes in structure, function, and regional connectivity in early life, ultimately stabilizing in early adulthood. Pathways between these two structures underlie many forms of emotional learning, including the extinction of conditioned fear. Here we sought to characterize changes in extinction-related medial PFC (mPFC) → amygdala functional connectivity across development that might explain adolescent impairments in extinction. The retrograde tracer Fluorogold was infused into the amygdala of postnatal day (P)22–23 (juvenile), P31-32 (adolescent), or ≥ P69 (adult) rats, which were then exposed to fear conditioning and extinction training. Brains were collected following extinction or context exposure and processed for expression of pMAPK (as a marker of learning-dependent plasticity) in prelimbic (PL) and infralimbic (IL) amygdala-projecting neurons. Consistent with previous findings, amygdala-projecting mPFC neurons were located primarily in layers (L)II/III and V of the mPFC. We noted that mPFC LII/III projected predominantly to the ipsilateral basolateral amygdala, whereas LV projected bilaterally and targeted multiple amygdalar nuclei. Extinction was not associated with changes in extinction-related plasticity in the PL-amygdala pathways in any age group. No changes were seen in LII/III of the IL, but extinction-related plasticity in LV amygdala-projecting IL neurons decreased linearly across development. These findings suggest that extinction-related functional connectivity between the IL and the amygdala undergoes fundamental changes across development that may contribute to alterations in fear suppression across development.

The presentation of novel stimuli induces a reliable dopamine release in the insular cortex (IC) from the ventral tegmental area (VTA). The novel stimuli could be associated with motivational and emotional signals induced by cortical glutamate release from the basolateral amygdala (BLA). Dopamine and glutamate are essential for acquiring and maintaining behavioral tasks, including visual and taste recognition memories. In this study, we hypothesize that the simultaneous activation of dopaminergic and glutamatergic projections to the neocortex can underlie synaptic plasticity. High-frequency stimulation of the BLA-IC circuit has demonstrated a reliable long-term potentiation (LTP), a widely acknowledged synaptic plasticity that underlies memory consolidation. Therefore, the concurrent optogenetic stimulation of the insula’s glutamatergic and dopaminergic terminal fibers would induce reliable LTP. Our results confirmed that combined photostimulation of the VTA and BLA projections to the IC induces a slow-onset LTP. We also found that optogenetically-induced LTP in the IC relies on both glutamatergic NMDA receptors and dopaminergic D1/D5 receptors, suggesting that the combined effects of these neurotransmitters can trigger synaptic plasticity in the neocortex. Overall, our findings provide compelling evidence supporting the essential role of both dopaminergic and glutamatergic projections in modulating synaptic plasticity within the IC. Furthermore, our results suggest that the synergistic actions of these projections have a pivotal influence on the formation of motivational memories.

Memory is critical for many cognitive functions, from remembering facts, to learning complex environmental rules. While memory encoding occurs during wake, memory consolidation is associated with sleep-related neural activity. Further, research suggests that individual differences in alpha frequency during wake (∼7 – 13 Hz) modulate memory processes, with higher individual alpha frequency (IAF) associated with greater memory performance. However, the relationship between wake-related EEG individual differences, such as IAF, and sleep-related neural correlates of memory consolidation has been largely unexplored, particularly in a complex rule-based memory context. Here, we aimed to investigate whether wake-derived IAF and sleep neurophysiology interact to influence rule learning in a sample of 35 healthy adults (16 males; mean age = 25.4, range: 18 – 40). Participants learned rules of a modified miniature language prior to either 8hrs of sleep or wake, after which they were tested on their knowledge of the rules in a grammaticality judgement task. Results indicate that sleep neurophysiology and wake-derived IAF do not interact but modulate memory for complex linguistic rules separately. Phase-amplitude coupling between slow oscillations and spindles during non-rapid eye-movement (NREM) sleep also promoted memory for rules that were analogous to the canonical English word order. As an exploratory analysis, we found that rapid eye-movement (REM) sleep theta power at posterior regions interacts with IAF to predict rule learning and proportion of time in REM sleep predicts rule learning differentially depending on grammatical rule type. Taken together, the current study provides behavioural and electrophysiological evidence for a complex role of NREM and REM sleep neurophysiology and wake-derived IAF in the consolidation of rule-based information.