Learning & memory最新文献

An inability to reduce fear in nonthreatening environments characterizes many anxiety disorders. The pathway from the ventral subiculum (vSUB) to the bed nucleus of the stria terminalis (BNST) is more active in safe contexts than in aversive ones, as indexed by FOS expression. Here, we used chemogenetic techniques to specifically activate the vSUB-BNST pathway during both context and cued fear expression by expressing a Cre-dependent hM3D(Gq) receptor in BNST-projecting vSUB neurons. Activation of the vSUB-BNST pathway reduced context but not cued fear expression. These data suggest that the vSUB-BNST pathway contributes to behavioral responses to nonaversive contexts.

Retrieving existing memories before new learning can lead to retroactive facilitation. Three experiments examined whether interpolated retrieval is associated with retroactive facilitation and memory interdependence that reflects integrative encoding. Participants studied two lists of cue-response word pairs that repeated across lists (A-B, A-B), appeared in list 1 (A-B, -), or included the same cues with changed responses in each list (A-B, A-C). For A-B, A-C pairs, the tasks interpolated between lists required recall of list 1 (B) responses (with or without feedback) or restudy of complete list 1 (A-B) pairs. In list 2, participants only studied pairs (experiment 1) or studied pairs, attempted to detect changed (C) responses, and attempted to recall list 1 responses for detected changes (experiments 2 and 3). On a final cued recall test, participants attempted to recall list 1 responses, indicated whether responses changed between lists, and if so, attempted to recall list 2 responses. Interpolated retrieval was associated with subsequent retroactive facilitation and greater memory interdependence for B and C responses. These correlational findings are compatible with the view that retrieval retroactively facilitates memories, promotes coactivation of existing memories and new learning, and enables integrative encoding that veridically binds information across episodes.

Fear conditioning is a laboratory paradigm commonly used to investigate aversive learning and memory. In context fear conditioning, a configuration of elemental cues (conditioned stimulus [CTX]) predicts an aversive event (unconditioned stimulus [US]). To quantify context fear acquisition in humans, previous work has used startle eyeblink responses (SEBRs), skin conductance responses (SCRs), and verbal reports, but different quantification methods have rarely been compared. Moreover, preclinical intervention studies mandate recall tests several days after acquisition, and it is unclear how to induce and measure context fear memory retention over such a time interval. First, we used a semi-immersive virtual reality paradigm. In two experiments (N = 23 and N = 28), we found successful declarative learning and memory retention over 7 d but no evidence of other conditioned responses. Next, we used a configural fear conditioning paradigm with five static room images as CTXs in two experiments (N = 29 and N = 24). Besides successful declarative learning and memory retention after 7 d, SCR and pupil dilation in response to CTX onset differentiated CTX⁺/CTX^- during acquisition training, and SEBR and pupil dilation differentiated CTX⁺/CTX^- during the recall test, with medium to large effect sizes for the most sensitive indices (SEBR: Hedge's g = 0.56 and g = 0.69; pupil dilation: Hedge's g = 0.99 and g = 0.88). Our results demonstrate that with a configural learning paradigm, context fear memory retention can be demonstrated over 7 d, and we provide robust and replicable measurement methods to this end.

Prefrontal cortical and striatal areas have been identified by inactivation or lesion studies to be required for behavioral flexibility, including selecting and processing of different types of information. In order to identify these networks activated selectively during the acquisition of new reward contingency rules, rats were trained to discriminate orientations of bars presented in pseudorandom sequence on two video monitors positioned behind the goal sites on a T-maze with return arms. A second group already trained in the visual discrimination task learned to alternate left and right goal arm visits in the same maze while ignoring the visual cues still being presented. In each experimental group, once the rats reached criterion performance, the brains were prepared after a 90-min delay for later processing for c-fos immunohistochemistry. While both groups extinguished a prior strategy and acquired a new rule, they differed by the identity of the strategies and previous learning experience. Among the 28 forebrain areas examined, there were significant increases in the relative density of c-fos immunoreactive cell bodies after learning the second rule in the prefrontal cortex cingulate, the prelimbic and infralimbic areas, the dorsomedial striatum and the core of the nucleus accumbens, the ventral subiculum, and the central nucleus of the amygdala. These largely correspond to structures previously identified in inactivation studies, and their neurons fire synchronously during learning and strategy shifts. The data suggest that this dynamic network may underlie reward-based selection for action-a type of cognitive flexibility.

Glucocorticoids are potent memory modulators that can modify behavior in an adaptive or maladaptive manner. Elevated glucocorticoid levels after learning promote memory consolidation at recent time points, but their effects on remote time points are not well established. Here we set out to assess whether corticosterone (CORT) given after learning modifies remote fear memory. To that end, mice were exposed to a mild auditory fear conditioning paradigm followed by a single 2 mg/kg CORT injection, and after 28 d, auditory memory was assessed. Neuronal activation was investigated using immunohistochemistry for the immediate early gene c-Fos, and coactivation of brain regions was determined using a correlation matrix analysis. CORT-treated mice displayed significantly less remote auditory memory retrieval. While the net activity of studied brain regions was similar compared with the control condition, CORT-induced remote memory impairment was associated with altered correlated activity between brain regions. Specifically, connectivity of the lateral amygdala with the basal amygdala and the dorsal dentate gyrus was significantly reduced in CORT-treated mice, suggesting disrupted network connectivity that may underlie diminished remote memory retrieval. Elucidating the pathways underlying these effects could help provide mechanistic insight into the effects of stress on memory and possibly provide therapeutic targets for psychopathology.

Neuropeptides are widely used as neurotransmitters in vertebrates and invertebrates. In vertebrates, a detailed understanding of their functions as transmitters has been hampered by the complexity of the nervous system. The marine mollusk Aplysia, with a simpler nervous system and many large, identified neurons, presents several advantages for addressing this question and has been used to examine the roles of tens of peptides in behavior. To screen for other peptides that might also play roles in behavior, we observed immunoreactivity in individual neurons in the central nervous system of adult Aplysia with antisera raised against the Aplysia peptide FMRFamide and two mammalian peptides that are also found in Aplysia, cholecystokinin (CCK) and neuropeptide Y (NPY), as well as serotonin (5HT). In addition, we observed staining of individual neurons with antisera raised against mammalian somatostatin (SOM) and peptide histidine isoleucine (PHI). However, genomic analysis has shown that these two peptides are not expressed in the Aplysia nervous system, and we have therefore labeled the unknown peptides stained by these two antibodies as X_SOM and X_PHI There was an area at the anterior end of the cerebral ganglion that had staining by antisera raised against many different transmitters, suggesting that this may be a modulatory region of the nervous system. There was also staining for X_SOM and, in some cases, FMRFamide in the bag cell cluster of the abdominal ganglion. In addition, these and other studies have revealed a fairly high degree of colocalization of different neuropeptides in individual neurons, suggesting that the peptides do not just act independently but can also interact in different combinations to produce complex functions. The simple nervous system of Aplysia is advantageous for further testing these ideas.

While fear generalizes widely, extinction is stimulus-specific. Using a hybrid conditioning/episodic memory paradigm, subjects encoded nonrepeating category exemplars during fear conditioning and extinction. Twenty-four hours later, a surprise memory test included old, similar, and novel category exemplars. Results showed strong dissociation between pattern completion (generalization) and pattern separation (discrimination) in episodic memory for items encoded during fear conditioning versus extinction, respectively. These data suggest that directly threat-conditioned stimuli are better recognized at the expense of mnemonic precision, whereas discrimination is enhanced for extinguished stimuli. Overly precise extinction memory may be a contributing factor to fear relapse.

Training on one task (task A) can disrupt learning on a subsequently trained task (task B), illustrating anterograde learning interference. We asked whether the induction of anterograde learning interference depends on the learning stage that task A has reached when the training on task B begins. To do so, we drew on previous observations in perceptual learning in which completing all training on one task before beginning training on another task (blocked training) yielded markedly different learning outcomes than alternating training between the same two tasks for the same total number of trials (interleaved training). Those blocked versus interleaved contrasts suggest that there is a transition between two differentially vulnerable learning stages that is related to the number of consecutive training trials on each task, with interleaved training presumably tapping acquisition, and blocked training tapping consolidation. Here, we used the blocked versus interleaved paradigm in auditory perceptual learning in a case in which blocked training generated anterograde-but not its converse, retrograde-learning interference (A→B, not B←A). We report that anterograde learning interference of training on task A (interaural time difference discrimination) on learning on task B (interaural level difference discrimination) occurred with blocked training and diminished with interleaved training, with faster rates of interleaving leading to less interference. This pattern held for across-day, within-session, and offline learning. Thus, anterograde learning interference only occurred when the number of consecutive training trials on task A surpassed some critical value, consistent with other recent evidence that anterograde learning interference only arises when learning on task A has entered the consolidation stage.

The hippocampus supports distinctive encoding, enabling discrimination of perceptions from similar memories. Here, an experimental and individual differences approach examined the role of encoding quality in the classification of similar lures. An object recognition task included thought probes during study and similar lures at test. On-task study reports were associated with lure discrimination in within-subject and between-subjects analyses. Within-subject on-task reports were also associated with false classifications of lures as studied objects. These results are compatible with the view that quality encoding supports memory-based rejection of lures but also engenders false alarms when perceptions and memories are inaccurately compared.