Learning & memory最新文献

Emotional intensity can produce both optimal and suboptimal effects on learning and memory. While emotional events tend to be better remembered, memory performance can follow an inverted U-shaped curve with increasing intensity. The strength of Pavlovian conditioning tends to increase linearly with the intensity of the aversive outcome, but leads to greater stimulus generalization. Here, we combined elements of episodic memory and Pavlovian conditioning into a single paradigm to investigate the effects of varying outcome intensities on conditioned fear responses and episodic memory. Participants encoded trial-unique images from two semantic categories as conditioned stimuli (CS⁺ and CS^-) before (preconditioning), during, and after (extinction) acquisition. We systematically varied the intensity of the unconditioned stimulus (US) during acquisition between-groups as a nonaversive tone, a low-intensity electrical shock, or a high-intensity electrical shock paired with a loud static noise. Results showed that conditioned skin conductance responses scaled linearly with US intensity during acquisition, with a high-intensity US leading to greater resistance to extinction and stronger 24 h fear recovery. However, 24 h recognition memory produced an inverted U-shaped relationship, with better recognition memory for CSs encoded before (retroactive), during, and following conditioning using a low-intensity US. These findings suggest a dissociation between optimal levels of emotional intensity on explicit and implicit learning and memory performance.

Mammals have evolved with a range of innate drives, such as thirst and hunger, that promote motivated behaviors to ensure survival. A drive for social engagement promotes social interaction and bond formation. While a stable social environment maintains the opportunity for resource sharing and protection, an additional benefit is provided by the social transmission of information. Social experiences, and information obtained from conspecifics, can be used to learn about threats and opportunities in the environment. This review examines the primary forms of social learning and how they can shape behavior. Additionally, while there is much known about the effects of stress on learning and memory, there is much less known about its effects on social learning and memory. This review will therefore dissect the major factors that contribute to social learning and propose how stress may impact these factors. This may serve as a way to formulate new hypotheses about how stress might impact social learning and the effects of social experiences on behavior.

Stress can have profound impacts on memory. However, the directionality of stress effects on memory varies widely across studies, some showing enhancement while others showing impairment. This variability has been attributed to the Yerkes-Dodson Law, which proposes a U-shaped pattern such that too little or too much stress may be associated with cognitive dysfunction. The impact of stress on memory may also depend on what aspects of memory are being measured (e.g., emotional content, gist vs. detail) and how stress is measured (e.g., physiological measures, self-report). Here, we aimed to examine how self-reported perceived stress in the current moment was associated with memory performance. We used an emotional memory task designed to tap into potential gist versus detail trade-offs of stress impacting memory (e.g., target recognition, lure discrimination). Participants (ages 18-35) reported their current level of perceived stress. We replicated prior work showing impaired emotional relative to neutral lure discrimination in young adults in support of a gist versus detail trade-off in emotional memory. However, those with low and high current perceived stress showed better emotional lure discrimination compared to those with moderate current perceived stress. These results are in line with the Yerkes-Dodson Law but suggest that the directionality of the impact of stress on memory may depend on the type of memory measured. Low and high current perceived stress was associated with greater detailed memory, especially for emotional information, which may be maladaptive given gist vs. detail trade-offs in emotional memory.

The lateral entorhinal cortex (LEC) contains glutamatergic projections that innervate the nucleus accumbens (NAc) and may be involved in the encoding of contextual associations with both positive and negative valences, such as those encountered in drug cues or fear conditioning. To determine whether LEC-NAc neurons are activated by the encoding and recall of contexts associated with cocaine or footshock, we measured c-fos expression in these neurons and found that LEC-NAc neurons are activated in both contexts. Specifically, activation patterns of the LEC-NAc were observed in a novel context and reexposure to the same context, highlighting the specific role for LEC-NAc neurons in encoding rather than the valence of a specific event-related memory. Using a combination of circuit-specific chemogenetic tools and behavioral assays, we selectively inactivated LEC-NAc neurons in mice during the encoding and retrieval of memories of contexts associated with cocaine or footshock. Chemogenetic inactivation of LEC-NAc neurons impaired the formation of both positive and negative context-associated memories without affecting the retrieval of an established memory. This finding suggests a critical role for this circuit in the initial encoding of contextual associations. In summary, LEC-NAc neurons facilitate the encoding of contextual information, guiding motivational behaviors without directly mediating the hedonic or aversive properties of these associations.

Binding of arbitrary information into distinct memory representations that can be used to guide behavior is a hallmark of relational memory. What is and is not bound into a memory representation and how those things influence the organization of that representation remain topics of interest. While some information is intentionally and effortfully bound-often the information that is consistent with task goals or expectations about what information may be required later-other information appears to be bound automatically. The present set of experiments sought to investigate whether spatial memory would be systematically influenced by the presence and absence of distinct categories of stimuli on a spatial reconstruction task. In this task, participants must learn multiple item-location bindings and place each item back in its studied location after a short delay. Across three experiments, participants made significantly more within-category errors (i.e., misassigning one item to the location of a different item from the same category) than between-category errors (i.e., misassigning one item to the location of an item from a different category) when categories were perceptually or semantically distinct. These data reveal that category information contributed to the organization of the memory representation and influenced spatial reconstruction performance. Together, these results suggest that categorical information can influence memory organization, and not always to the benefit of overall task performance.

Memory formation is contingent on molecular and structural changes in neurons in response to learning stimuli-a process known as neuronal plasticity. The initiation step of mRNA translation is a gatekeeper of long-term memory by controlling the production of plasticity-related proteins in the brain. The mechanistic target of rapamycin complex 1 (mTORC1) controls mRNA translation, mainly through phosphorylation of the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs) and ribosomal protein S6 kinases (S6Ks). mTORC1 signaling decreases throughout brain development, starting from the early postnatal period. Here, we discovered that in mice, the age-dependent decrease in mTORC1 signaling occurs selectively in excitatory but not inhibitory neurons. Using a gene conditional knockout (cKO) strategy, we demonstrate that either up- or downregulating the mTORC1-4E-BP2 axis in GAD65 inhibitory interneurons, but not excitatory neurons, results in long-term object recognition and object location memory deficits. Our data indicate that the mTORC1 pathway in inhibitory but not excitatory neurons plays a key role in memory formation.

Memory updating is essential for integrating new information into existing representations. However, this process could become maladaptive in conditions like post-traumatic stress disorder (PTSD), when fear memories generalize to neutral contexts. Previously, we have shown that contextual fear memory malleability in rats requires activation of M1 muscarinic acetylcholine receptors in the dorsal hippocampus. Here, we investigated the involvement of this mechanism in the transfer of contextual fear memories to other contexts using a novel fear memory updating paradigm. Following brief reexposure to a previously fear conditioned context, male rats (n = 8-10/group) were placed into a neutral context to evaluate the transfer of fear memory. We also infused the selective M1 receptor antagonist pirenzepine into the dorsal hippocampus before memory reactivation to try to block this effect. Results support the hypothesis that fear memory can be updated with novel contextual information, but only if rats are reexposed to the originally trained context relatively recently before the neutral context; evidence for transfer was not seen if the fear memory reactivation was omitted or if it occurred 6 h before neutral context exposure. The transferred fear persisted for 4 weeks, and the effect was blocked by M1 antagonism. These findings strongly suggest that fear transfer requires reactivation and destabilization of the original fear memory. The novel preclinical model introduced here, and its implication of muscarinic receptors in this process, could therefore inform therapeutic strategies for PTSD and similar conditions.

G protein-gated inwardly rectifying K⁺ (GIRK) channels mediate the postsynaptic inhibitory effect of many neurotransmitters in the hippocampus and are implicated in neurological disorders characterized by cognitive deficits. Here, we show that enhancement or suppression of GIRK channel activity in dorsal CA1 pyramidal neurons disrupted novel object recognition in mice, without impacting open field activity or avoidance behavior. Contextual fear learning was also unaffected, but extinction of contextual fear was disrupted by suppression of GIRK channel activity in male mice. Thus, the strength of GIRK channel activity in dorsal CA1 pyramidal neurons regulates select cognitive task performance in mice.

Previous studies have shown that the formation of new memories can be influenced by prior experience. This includes work using Pavlovian fear conditioning in rodents that has shown that an initial fear conditioning experience can become associated with and facilitate the acquisition of new fear memories, especially when they occur close together in time. However, most of the prior studies used only males as subjects, resulting in questions about the generalizability of the findings from this work. Here we tested whether prior contextual fear conditioning would facilitate later learning of cued fear conditioning in both male and female rats, and if there were differences based on the interval between the two conditioning episodes. Our results showed that levels of cued fear were not influenced by prior contextual fear conditioning or by the interval between training; however, females showed lower levels of cued fear. Freezing behavior in the initial training context differed by sex, with females showing lower levels of contextual fear, and by the type of initial training, with rats given delayed shock showing higher levels of fear than rats given immediate shock during contextual fear conditioning. These results indicate that contextual fear conditioning does not prime subsequent cued fear conditioning and that female rats express lower levels of cued and contextual fear conditioning than males.