Learning & memory最新文献

Individual differences in reinforcement sensitivity may shape associative learning processes. We investigated how behavioral inhibition and activation systems (BIS/BAS), that is, variation in avoidance versus approach tendencies, modulate awareness of stimulus-outcome contingencies during appetitive conditioning (with monetary rewards) and aversive conditioning (with electric shocks) in N = 62 uninstructed participants (54 women). BAS "reward responsiveness" was found to predict subjective expectancy of appetitive (but not aversive) outcomes, independent of extraversion and neuroticism. BIS was unrelated to contingency awareness. Results highlight reward sensitivity as a distinct trait, facilitating conscious detection and processing of reward contingencies.

Memory generalization involves the transfer of conditioned fear responses to novel contexts, a phenomenon observed in systems consolidation, whereby a time-dependent reduction in discrimination precision occurs due to the reorganization of brain regions supporting memory retrieval. To understand the fine temporal structure of this process across sexes, young adult female and male rats were trained in contextual fear conditioning and tested in the same or one of three distinct novel contexts at 2, 28, or 45 days post-training. Neutral contexts were designed to allow graded levels of fear expression relative to the training context, and sex differences were evident at the recent memory test. This pattern, however, disappeared over time due to partial generalization, with fear converging into similar, higher values, grouped into two levels for both sexes. In all experiments, females were better discriminators and displayed lower fear responses than males, apparently prioritizing different sensory modalities, with multivariate analysis suggesting that chamber size was salient for females and floor texture for males. This study is the first to compare fear responses between adult female and male rats across multiple neutral contexts and time points revealing several dimorphic findings.

Extinguished responses are prone to renew outside the context where extinction occurred. Two experiments compared extinction and renewal following either a 1 day conditioning-to-extinction interval or a 27 day interval. Rats received tone-shock pairings in Context A, and extinction in Context B. Testing occurred in Context A (Experiment 1) or C (Experiment 2). Extinction occurred at a similar rate after both retention intervals. Robust renewal was also observed and was not affected by the conditioning-to-extinction retention interval. Results are discussed with respect to prior research on the timing of extinction, the neurobiology of recent and remote memory retrieval, and translational relevance.

Insufficient sleep compromises the cAMP signaling pathway in the hippocampus, negatively impacting hippocampus-dependent memory. In the current study, we explored whether selective PDE4B or selective PDE4D inhibition can improve hippocampus-dependent spatial memory in the object location test (OLT) in mice after sleep deprivation (SD). The results demonstrated that SD impaired the OLT performance, and both A-33 and zatolmilast protected against the negative consequences of SD when administered at the start and middle of the SD period. These findings suggest that both PDE4B and PDE4D subfamilies contribute to the beneficial effect of PDE4 inhibition against SD-induced memory consolidation impairment.

Social anxiety disorder (SAD) stands as a prevalent psychiatric condition characterized by the apprehension of scrutiny and embarrassment in social settings, leading to anxiety symptoms, avoidance behaviors, and impaired social and occupational functioning. Despite the efficacy of various evidence-based treatments, a substantial portion of patients remain unresponsive. In this study, we used the socially enriched environment test (SEE, developed in our laboratory) to assess behaviors associated with social anxiety disorder after intervention, using various therapeutic strategies. We tested, in male mice, the effects of acute oxytocin injection, behavioral extinction, and high-frequency stimulation of the infralimbic (IL) cortex on social anxiety induced by a social fear conditioning paradigm. The SEE test revealed three behavioral changes, including reduced social interaction, reduced collective object exploration, and increased freezing behavior. Oxytocin and high-frequency stimulation of the IL cortex affected all these behavioral changes, while extinction training affected two (social interaction and freezing behavior). In conclusion, the SEE test is a reliable tool for exploring social anxiety behaviors in mice. Moreover, it can be used to evaluate different therapeutic approaches, providing valuable information on innovative therapeutic strategies for the effective treatment of SAD.

Classic models propose that forming lasting visual memories involves coordinated interactions between visually selective neocortical structures and the hippocampus during memory consolidation. However, the precise role of visually selective neocortical structures in memory consolidation remains elusive, given their potential contributions spanning from initial perceptual encoding to subsequent memory reactivation. We capitalized on a unique opportunity, involving direct recording from the posterior parahippocampus and its subsequent resection in a neurological patient, to investigate the impact of scene-selective neocortical lesions on visual memory consolidation. First, with intracranial EEG, we confirmed the functional relevance of the patient's resected tissues in representing a specific visual category, in this case, scene images. Subsequently, we identified disruption of memory for scenes relative to faces and objects during the participant's postoperative visit. This finding prompted a comprehensive analysis of visual memory across different visual categories in this participant, as well as an examination of similar functions in other neurological patients with intact parahippocampi and a cohort of online participants. Through these within- and between-participant comparisons, we identified greater time-dependent reduction in visual memory for scene images following the resection of the posterior parahippocampus. Importantly, these changes in memory retention could not be attributed to a general reduction in initial memory encoding following neocortical lesions. Our findings, therefore, suggest that reactivating scene-selective neocortical areas is essential for converting transient visual perceptual experiences into lasting long-term scene memories.

Spatial working memory (SWM) relies on the integrity of the medial septum area (MSA) and its ability to drive theta (4-12 Hz) oscillations in the hippocampus. This study tested the hypothesis that optogenetic theta stimulation of the MSA would enhance choice accuracy on a hippocampus-dependent task in rats. We delivered either excitatory or control theta stimulation during the delay period (10 or 30 sec) of a delayed alternation (DA) task. We show that MSA theta stimulation improved choice accuracy on the 30 sec delay trials, providing strong support for the notion that MSA theta stimulation boosts SWM.

Evidence suggests a role for monoubiquitination of histone H2B, a regulator of increased gene transcription, in memory formation. However, whether monoubiquitination of histone H2A (H2Aubi), a transcriptional repressor, is involved in memory formation has not been explored. We found global and gene-specific decreases in H2Aubi in the amygdala following fear conditioning. H2Aubi decreased at Pten, an inhibitor of PI3K-AKT-mTOR signaling, which occurred concurrently with increases in PTEN expression. CRISPR-dCas9 mediated upregulation of the H2Aubi ligase, Ring1b, in the amygdala enhanced contextual memory. These results suggest that decreases in transcriptionally repressive H2Aubi in the amygdala functions to constrain fear memory strength.

Sign-tracking, a conditioned response in which animals engage with reward-predictive cues, is a powerful behavioral tool for assessing Pavlovian motivation. In rodents, it is most frequently studied via automatic readouts, such as deflections of levers that act as reward cues. These readouts have been immensely helpful, but they may not be ideal for some tasks and paradigms. For example, animals can show a range of sign-tracking responses to a lever cue that do not result in lever deflection, and a reduction in deflections when animals are exposed to an omission contingency (i.e., when lever deflection cancels reward) hides the fact that the animals are still sign-tracking in other ways. Here, we analyzed the behavior of sign-tracking animals through both video monitoring and automatic task readouts in Pavlovian conditioning. This analysis aided in the classification of sign-tracking animals and revealed that lever deflections do not result from any identifiable pattern of sign-tracking. We then used omission and extinction procedures to unmask detailed behavior changes that can only be detected with video data. Automated readouts showed similar reductions of lever deflection in both task conditions. However, detailed behavioral analysis revealed quite distinct behavioral adaptations to these conditions with sign-tracking decreasing entirely during extinction while many sign-tracking behaviors (biting, sniffing, etc.) seemed to remain persistent during omission despite the decrease in deflections. Detailed behavioral analysis was thus critical for capturing sign-tracking maintenance, persistence, and loss.

Apolipoprotein E (ApoE) is a protein that is important for lipid storage, transport, and metabolism. APOE gene variants are associated with Alzheimer's disease, as well as attentional function in healthy humans. Previous research has shown that Apoe transcription is increased following stimulation of the pathway between the locus coeruleus (LC) and frontal cortex (FC) in mice. This result suggests that Apoe may affect attentional function by virtue of its expression in circuits that control attention. Does Apoe causally regulate attention, or is its expression simply a byproduct of neuronal activity in the LC and FC? To answer this question, we synthetically induced Apoe transcription in the FC of male and female mice, and subsequently tested their ability to learn a touchscreen-based rodent version of the continuous performance test of sustained attention (the rCPT). We found that increased Apoe transcription impaired performance when attentional demand was increased in male mice, while in female mice, increased Apoe transcription significantly accelerated rCPT learning. We further found that this increase in Apoe transcription affected one metric of the open field test, as well as cellular activity in the FC in a sex-dependent manner. The results of this study provide insight into how Apoe causally regulates translationally relevant behaviors in rodent models.