Learning & Memory

Exposure-based therapy is effective in treating anxiety, but a return of fear in the form of relapse is common. Exposure is based on the extinction of Pavlovian fear conditioning. Both animal and human studies point to increased arousal during immediate compared to delayed extinction (>+24 h), which presumably impairs extinction learning and increases the subsequent return of fear. Impaired extinction learning under arousal might interfere with psychotherapeutic interventions. The aim of the present study was to investigate whether arousal before extinction differs between extinction groups and whether arousal before extinction predicts the return of fear in a later (retention) test...

Posttranslational modification of histone proteins is critical for memory formation. Recently, we showed that monoubiquitination of histone H2B at lysine 120 (H2Bub) is critical for memory formation in the hippocampus. However, the transcriptome controlled by H2Bub remains unknown. Here, we found that fear conditioning in male rats increased or decreased the expression of 86 genes in the hippocampus but, surprisingly, siRNA-mediated knockdown of the H2Bub ligase, Rnf20 , abolished changes in all but one of these genes...

From early in life, we encounter both controllable environments, in which our actions can causally influence the reward outcomes we experience, and uncontrollable environments, in which they cannot. Environmental controllability is theoretically proposed to organize our behavior. In controllable contexts, we can learn to proactively select instrumental actions that bring about desired outcomes. In uncontrollable environments, Pavlovian learning enables hard-wired, reflexive reactions to anticipated, motivationally salient events, providing "default" behavioral responses...

Lapses in attention can negatively impact later memory of an experience. Attention and encoding resources are thought to decline as more experiences are encountered in succession, accounting for the primacy effect in which memory is better for items encountered early compared to late in a study list. However, accessing prior knowledge during study can facilitate subsequent memory, suggesting a potential avenue to counteract this decline. Here, we investigated the extent to which semantic associations-shared meaning between experiences-can counteract declines in encoding resources...

Memories of prior rewards bias our actions and future decisions. To determine the neural correlates of an appetitive associative learning task, we trained male mice to discriminate a reward-predicting cue over the course of 7 d. Encoding, recent recall, and remote recall were investigated to determine the areas of the brain recruited at each stage of learning. Using cFos as a proxy for neuronal activity, we found unique brain-wide patterns of activity across days that seem to correlate with distinct stages of learning...

The odor span task (OST) infers working memory capacity (WMC) by requiring rodents to discriminate between previously presented and session-novel odors to obtain a hidden food reward. Here, rats' responses to session-novel odors and food rewards were assessed to determine whether rats use mitigating strategies in the OST. Rats accurately responded to session-novel odors but also reliably responded to the food reward alone and performed at chance when both a session-novel odor and food reward were presented in separate locations...

We investigated whether retrograde amnesia for the stress-induced impairment of extinction retrieval shares similar characteristics with original acquisition memories. The first experiment demonstrated that cycloheximide administered shortly after a single restraint stress session alleviated the impairment of extinction retrieval but not when administered following a longer delay (i.e., the amnesia for stress is time-dependent). A second experiment showed that the retrograde amnesia for stress could be alleviated by a second brief exposure to the stressor...

Memory retrieval is strikingly susceptible to external states (environment) and internal states (mood states and alcohol), yet we know little about the underlying mechanisms. We examined how internally generated states influence successful memory retrieval using the functional magnetic resonance imaging (fMRI) of laboratory mice during memory retrieval. Mice exhibited a strong tendency to perform memory retrieval correctly only in the reinstated mammillary body-inhibited state, in which mice were trained to discriminate auditory stimuli in go/no-go tasks...

There is debate as to whether a time-dependent transformation of the episodic-like memory network is observed for nonepisodic tasks, including procedural motor memory. To determine how motor memory networks reorganize with time and practice, mice performed a motor task in a straight alley maze for 1 d (recent), 20 d of continuous training (continuous), or testing 20 d after the original training (remote), and then regional c-Fos expression was assessed. Elevated hippocampal c-Fos accompanied remote, but not continuous, motor task retrieval after 20 d, suggesting that the hippocampus remains engaged for nonhabitual remote motor memory retrieval...

Male and female 3xTg-AD mice between 5 and 24 mo of age and their B6129F2/J wild-type controls were tested on a series of 18 olfactory discrimination and reversal tasks in an operant olfactometer. All mice learned the odor discriminations and reversals to a criterion of 85% correct, but the 3xTg-AD mice made fewer errors than the B6129F2/J mice in the odor discriminations and in the first six reversal learning tasks. Many mice showed evidence of near errorless learning, and on the reversal tasks the 3xTg-AD mice showed more instances of near errorless learning than the B6129F2/J mice...

The mnemonic discrimination task (MDT) is a widely used cognitive assessment tool. Performance in this task is believed to indicate an age-related deficit in episodic memory stemming from a decreased ability to pattern-separate among similar experiences. However, cognitive processes other than memory ability might impact task performance. In this study, we investigated whether nonmnemonic decision-making processes contribute to the age-related deficit in the MDT. We applied a hierarchical Bayesian version of the Ratcliff diffusion model to the MDT performance of 26 younger and 31 cognitively normal older adults...

This study investigated how humans process probabilistic-associated information when encountering varying levels of uncertainty during implicit visual statistical learning. A novel probabilistic cueing validation paradigm was developed to probe the representation of cues with high (75% probability), medium (50%), low (25%), or zero levels of predictiveness in response to preceding targets that appeared with high (75%), medium (50%), or low (25%) transitional probabilities (TPs). Experiments 1 and 2 demonstrated a significant negative association between cue probe identification accuracy and cue predictiveness when these cues appeared after high-TP but not medium-TP or low-TP targets, establishing exploration-like cue processing triggered by lower-uncertainty rather than high-uncertainty inputs...

An in vitro analog of learning that a food is inedible provided insight into mechanisms underlying the learning. Aplysia learn to stop responding to a food when they attempt but fail to swallow it. Pairing a cholinergic agonist with an NO donor or histamine in the Aplysia cerebral ganglion produced significant decreases in fictive feeding in response to the cholinergic agonist alone. Acetylcholine (ACh) is the transmitter of chemoreceptors sensing food touching the lips. Nitric oxide (NO) and histamine (HA) signal failed attempts to swallow food...

Historically, the development of valid and reliable methods for assessing higher-order cognitive abilities (e.g., rule learning and transfer) has been difficult in rodent models. To date, limited evidence supports the existence of higher cognitive abilities such as rule generation and complex decision-making in mice, rats, and rabbits. To this end, we sought to develop a task that would require mice to learn and transfer a rule. We trained mice to visually discriminate a series of images (image set, six total) of increasing complexity following three stages: (1) learn a visual target, (2) learn a rule (ignore any new images around the target), and finally (3) apply this rule in abstract form to a comparable but new image set...

To date, there is insufficient evidence to explain the role of adenosinergic receptors in the reconsolidation of long-term spatial memory. In this work, the role of the adenosinergic receptor family (A1, A2A, A2B, and A3) in this process has been elucidated. It was demonstrated that when infused bilaterally into the hippocampal CA1 region immediately after an early nonreinforced test session performed 24 h posttraining in the Morris water maze task, adenosine can cause anterograde amnesia for recent and late long-term spatial memory...

Fear memory formation and recall are highly regulated processes, with the central amygdala (CeA) contributing to fear memory-related behaviors. We recently reported that a remote fear memory engram is resident in the anterior basolateral amygdala (aBLA). However, the extent to which downstream neurons in the CeA participate in this engram is unknown. We tested the hypothesis that CeA neurons activated during fear memory formation are reactivated during remote memory retrieval such that a CeA engram participates in remote fear memory recall and its associated behavior...

While the benefits of sleep for associative memory are well established, it is unclear whether single-item memories profit from overnight consolidation to the same extent. We addressed this question in a preregistered, online study and also investigated how the temporal proximity between learning and sleep influences overnight retention. Sleep relative to wakefulness improved retention of item and associative memories to similar extents irrespective of whether sleep occurred soon after learning or following a prolonged waking interval...

Emotional memories are processed during sleep; however, the specific mechanisms are unclear. Understanding such mechanisms may provide critical insight into preventing and treating mood disorders. Consolidation of neutral memories is associated with the coupling of NREM sleep slow oscillations (SOs) and sleep spindles (SPs). Whether SO-SP coupling is likewise involved in emotional memory processing is unknown. Furthermore, there is an age-related emotional valence bias such that sleep consolidates and preserves reactivity to negative but not positive emotional memories in young adults and positive but not negative emotional memories in older adults...

Episodic memories are thought to be stabilized through the coordination of cortico-hippocampal activity during sleep. However, the timing and mechanism of this coordination remain unknown. To investigate this, we studied the relationship between hippocampal reactivation and slow-wave sleep up and down states of the retrosplenial cortex (RTC) and prefrontal cortex (PFC). We found that hippocampal reactivations are strongly correlated with specific cortical states. Reactivation occurred during sustained cortical Up states or during the transition from up to down state...

Sleep promotes the stabilization of memories in adulthood, with a growing literature on the benefits of sleep for memory in infants and children. In two studies, we examined the role of sleep in the retention and generalization of nonadjacent dependencies (NADs; e.g., a-X-b/c-X-d phrases) in an artificial language. Previously, a study demonstrated that over a delay of 4 h, 15 mo olds who nap after training retain a general memory of the NAD rule instead of memory for specific NADs heard during training. In experiment 1, we designed a replication of the nap condition used in the earlier study but tested 18-mo-old infants...