Neurobiology of Learning and Memory

Animals rely on learned cues to guide their behaviour for rewards such as food. The Pavlovian-instrumental transfer (PIT) task can be used to investigate the influence of Pavlovian stimuli on instrumental responding. Ghrelin, an orexigenic peptide, and its receptor, growth hormone secretagogue receptor 1A (GHS-R1A), has received growing interest for its role in reward-motivated learning and behaviours. A significant population of GHS-R1A have been identified within the ventral tegmental area (VTA), a critical node in the mesolimbic reward circuit that is necessary for the expression of PIT...

Preclinical studies show that inhibiting the actin motor ATPase nonmuscle myosin II (NMII) with blebbistatin (Blebb) in the basolateral amgydala (BLA) depolymerizes actin, resulting in an immediate, retrieval-independent disruption of methamphetamine (METH)-associated memory in male and female adult and adolescent rodents. The effect is highly selective, as NMII inhibition has no effect in other relevant brain regions (e.g., dorsal hippocampus [dPHC], nucleus accumbens [NAc]), nor does it interfere with associations for other aversive or appetitive stimuli, including cocaine (COC)...

In female rats and humans, reproductive experience (i.e., pregnancy) alters the behavioral, hormonal and molecular substrates of fear extinction. Here, we assessed whether the role of a central neural substrate of fear extinction, the basolateral amygdala (BLA), also changes following reproductive experience. Nulliparous (virgin) and primiparous (one prior pregnancy) female rats received infusions of the GABAA agonist, muscimol, to temporarily inactivate the BLA prior to fear conditioning or extinction training...

Classically interpreted as a competition between opposite memories (A vs B), anterograde interference (AI) also emerges in the absence of competing memories (A vs A), suggesting that mechanisms other than those involved in memory competition contribute to AI. To investigate this, we tested the hypothesis that extending motor practice would enhance a first memory, but come at the cost of reduced learning capabilities when subsequently exposed to a second learning session of the same task. Based on converging biological evidence, AI was expected to depend upon the degree of extended practice of the initial exposure...

This paper describes the relationship between performance in a decision-making task and the emergence of task-relevant representations. Participants learnt two tasks in which the appropriate response depended on multiple relevant stimuli and the underlying stimulus-outcome associations were governed by a latent feature that participants could discover. We divided participants into good and bad performers based on their overall classification rate and computed behavioural accuracy for each feature value. We found that participants with better performance had a better representation of the latent feature space...

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...

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...

The purpose of the present investigation was to test how acute stress and levels of circulating estrogens together influence acquisition and retention of spatial learning, as well as explorative behaviors in female rats. We used the hippocampus-dependent Open-field Tower Maze (OFTM) task to assess acquisition followed by a retention test (reacquisition) that was given 48 hours later. Immediately prior to acquisition, experimental rats were exposed to an acute restraint stress and were trained under bright lights...

The hippocampus is usually associated with recall memory, whereas its contribution to familiarity-based memory is debated. Growing evidence support the idea that this structure participates to any cognitive process performed on scene representations. In parallel, differences in functional specialisation and cortical connectivity were found across the longitudinal and transverse axes of the hippocampus. Here we reanalysed functional MRI data from 51 participants showing stronger engagement of the hippocampus in recall, familiarity-based recognition and rejection, and visual discrimination, of scenes compared to single objects...

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...

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...

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...

In the present studies, we assessed the effect of the 5-HT1A 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...

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...

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...

The deleterious effects of sleep loss on sleep-dependent memory and emotional function have been documented in the current literature. Yet, the effects of insomnia-induced chronic sleep disturbance on emotional short-term memory have been scarcely investigated. Twenty-one participants with subclinical insomnia disorder (SID) and 20 healthy participants (healthy control, HC) performed a delayed recognition task of emotional faces, and event-related potentials (ERPs) involved in memory encoding, retention, and retrieval of faces across different emotional valances were assessed...

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...

The Nociceptin/Orphanin FQ (N/OFQ) system has been shown to modulate various aspects of long-term memory. It is therefore important to study the effects on memory impairment by nociceptin receptor (NOP) agonists under preclinical development. In the present study, we investigated the effect of systemic injection of two small molecule selective NOP agonists, AT-202 and AT-524, in the object location memory task in male and female mice. Since high doses of NOP agonists have been shown to induce sedation, we first determined the sedative doses for the two compounds and found them to be higher in female than in male mice...

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...

Early life stress (ELS), including experiences with abuse and neglect, are related to several negative health outcomes in adulthood. One area that has received attention is the increased rate of substance abuse disorder in individuals who had experienced ELS. Given the critical role habitual behavior in the development of substance abuse, ELS may affect the trajectory of neural development such that habitual responding is more dominant than in individuals who did not experience ELS. Here, we examine learning of a probabilistic classification task (the Weather Prediction Task) in healthy young adults who reported significant ELS and those that did not...