Context extinction and associative learning in Lymnaea

Aerial respiratory behavior in the pond snail Lymnaea was operantly conditioned so that snails learned not to perform aerial respiration in a hypoxic environment. Snails were trained in either the standard context (no food odorant) or a carrot (food-odorant) context. An operant training procedure of two 45-min training sessions with a 1-h interval between the sessions followed by a third 45-min training session 18 h later was sufficient to produce associative learning and long-term memory (LTM) that persisted for at least 5 days. If, however, following the third operant training session snails received three 45-min extinction training sessions, with each extinction session separated by at least a 1-h interval, LTM was not observed when tested the following day. That is, the memory was extinguished. Extinction, however, did not occur if the context of the extinction training was different from the context of the associative training. That is, in the snails trained in the standard context, extinction did not occur if the extinction training sessions were performed in the food-odorant context and vice versa.     

Attentional mechanisms in learned predictiveness

Cues that reliably predict an outcome in an initial phase of training (Phase 1) are learned faster in a second phase of training (Phase 2) than cues that were unreliable in Phase 1. This result is observed despite objectively equal relationships between the cues and the outcomes in Phase 2, and consequently constitutes a nonnormative bias in learning. The present experiments sought to confirm that this learned predictiveness effect is the product of attentional processes (Experiment 1), and to test further whether these processes are under voluntary control or are automatic in nature (Experiment 2). In addition to the usual outcome prediction measure, eye-gaze behavior was also monitored. The results indicated an important role for top-down strategic attentional processes in the learned predictiveness task. In contrast, no evidence for an automatic attentional bias was found.     

Comparing elemental and configural associative theories in human causal learning: a case for attention

In two causal learning experiments with human participants, the authors compared various associative theories that assumed either elemental (unique cue, modified unique cue, replaced elements model, and Harris' model) or configural processing of stimuli (Pearce's theory and a modification of it). The authors used modified patterning problems initially suggested by Redhead and Pearce (1995). Predictions for all theories were generated by computer simulations. Both configural theories and the unique cue approach failed to account for the observations. The replaced elements model was able to account for part of the data, but only if the replacement parameters could vary across discrimination problems. The Harris model and the modified unique cue approach, assuming that the salience of stimuli decreases with an increasing number of stimuli in a compound, successfully accounted for all of our data. This success implies that attentional factors should be explicitly taken into account in associative learning theory.     

Attentional mechanisms associated with repressive distancing

This research explores the role of attentional shift and disengagement in repressive distancing. During a target-detection task in which emotional and neutral facial expressions were used as cues, participants received performance feedback intended to elicit a negative emotional reaction that rendered the task either threatening or not threatening to self-concept. When the task was perceived to threaten self-concept, repressors distanced themselves by rapidly disengaging their attention from the facial expressions rather than by slowly shifting or not shifting their attention to the facial expressions. Attentional disengagement was accompanied by sympathetic nervous system activity suggestive of a defense response. This research provides further insight into the nature and consequences of the interplay of dispositional tendencies, situational contexts, and higher order cognitive influences in attentional behavior.     

Comparison of the rates of associative change during acquisition and extinction

Five experiments used a compound test procedure to compare the rate parameters for the associative changes resulting from reinforcement and nonreinforcement. Experiments 1 and 4, using a magazine-approach procedure in rats, found initial acquisition to proceed more rapidly but to generalize less broadly than extinction. Experiments 2 and 5 repeated these observations in an autoshaping preparation with pigeons. Experiment 3 found no evidence for differential disruption of acquisition and extinction in testing. These results were obtained in a test procedure that compares responding with stimulus compounds in order to remove the differences in overall performance, which have complicated inferences about associative changes in earlier experiments.     

Persistent up-regulation of polyribosomes at synapses during long-term memory,reconsolidation, and extinction of associative memory

Local protein synthesis at synapses can provide a rapid supply of proteins to support synaptic changes during consolidation of new memories, but its role in the maintenance or updating of established memories is unknown. Consolidation requires new protein synthesis in the period immediately following learning, whereas established memories are resistant to protein synthesis inhibitors. We have previously reported that polyribosomes are up-regulated in the lateral amygdala (LA) during consolidation of aversive-cued Pavlovian conditioning. In this study, we used serial section electron microscopy reconstructions to determine whether the distribution of dendritic polyribosomes returns to baseline during the long-term memory phase. Relative to control groups, long-term memory was associated with up-regulation of polyribosomes throughout dendrites, including in dendritic spines of all sizes. Retrieval of a consolidated memory by presentation of a small number of cues induces a new, transient requirement for protein synthesis to maintain the memory, while presentation of a large number of cues results in extinction learning, forming a new memory. One hour after retrieval or extinction training, the distribution of dendritic polyribosomes was similar except in the smallest spines, which had more polyribosomes in the extinction group. Our results demonstrate that the effects of learning on dendritic polyribosomes are not restricted to the transient translation-dependent phase of memory formation. Cued Pavlovian conditioning induces persistent synapse strengthening in the LA that is not reversed by retrieval or extinction, and dendritic polyribosomes may therefore correlate generally with synapse strength as opposed to recent activity or transient translational processes.

The formation of long-term memory involves a consolidation phase in the period immediately after learning, during which new proteins are required to stabilize learning-induced synapse remodeling (Davis and Squire 1984; Mayford et al. 2012; Rosenberg et al. 2014; Segal 2017). There is evidence that local protein synthesis in dendrites is essential for consolidation of long-term memory and related forms of synaptic plasticity (Holt and Schuman 2013), but its exact role is not well understood. Dendritic translation can supply new proteins to synapses rapidly, and potentially with synapse-specific spatial precision. Thousands of mRNAs have been identified in dendrites, many of which encode synaptic proteins (Poon et al. 2006; Zhong et al. 2006; Cajigas et al. 2012; Tushev et al. 2018; Middleton et al. 2019), and mRNA is present in dendritic spines (Tiruchinapalli et al. 2003; Hafner et al. 2019). The ability of dendritic mRNAs to remain dormant until they are unmasked by synaptic activity (Doyle and Kiebler 2011; Buxbaum et al. 2014; Hutten et al. 2014) provides a mechanism for rapid and targeted translation at synapses. Synaptic activity during learning triggers a transient up-regulation of new synaptic proteins in dendrites (Redondo and Morris 2011; Moncada et al. 2015), and the spatiotemporal constraints on these new proteins strongly suggest that they are translated locally (Sajikumar et al. 2007; Doyle and Kiebler 2011). We have previously found by serial section transmission electron microscopy (ssTEM) volume reconstruction that polyribosomes and translation factors are up-regulated in dendritic spines in the rat lateral amygdala (LA) 1 h after cued aversive Pavlovian conditioning (Ostroff et al. 2010, 2017; Gindina et al. 2021). These polyribosomes presumably represent translation supporting consolidation, but no studies have addressed whether dendritic translation remains elevated or returns to baseline in the long-term memory phase.Cued aversive Pavlovian conditioning, also referred to as fear or threat conditioning, is an extensively studied learning paradigm in which a sensory cue is paired with an unpleasant stimulus—typically an auditory cue with a mild shock—to create an associative memory between the two (LeDoux 2000; Maren 2001). There is strong evidence that this memory is mediated by protein synthesis-dependent strengthening of LA synapses during a short window after learning. Enhanced synaptic transmission is observed in the LA after conditioning (McKernan and Shinnick-Gallagher 1997; Rogan et al. 1997; Sah et al. 2008), and consolidation requires protein synthesis in the LA immediately after training, but not 6 or 24 h later (Nader et al. 2000; Schafe and LeDoux 2000; Maren et al. 2003). The extracellular signal-regulated/mitogen-activated protein kinase (ERK/MAPK), which regulates translation (Kelleher et al. 2004), is transiently phosphorylated in the LA 1 h after learning, and this phosphorylation is required for both memory consolidation (Schafe et al. 2000) and synaptic plasticity in the LA (Huang et al. 2000; Schafe et al. 2008).Although dormant long-term memories are stable, retrieval induces a new labile phase called reconsolidation, during which the memory can be updated, weakened, or strengthened (Dudai 2012). As in consolidation, postretrieval inhibition of protein synthesis or ERK/MAPK phosphorylation in the LA impairs reconsolidation of the memory and associated synaptic plasticity (Nader et al. 2000; Duvarci et al. 2005; Doyere et al. 2007). A transient supply of necessary new proteins is available to synapses during reconsolidation (Orlandi et al. 2020), but whether these proteins are synthesized in dendrites is unknown. Both consolidation and reconsolidation are impaired by broad protein synthesis inhibitors, and there is substantial evidence that consolidation requires translation initiation, the step in which polyribosomes are formed (Gkogkas et al. 2010; Santini et al. 2014). Interestingly, one study found that inhibition of the predominant initiation process impaired consolidation but not reconsolidation, suggesting that the role of translation differs between the two processes (Hoeffer et al. 2011). Since polyribosomes can be stalled for later reactivation (Richter and Coller 2015), reconsolidation could rely on translation of pre-existing polyribosomes.Reconsolidation is triggered by a small number of retrieval cues, but retrieval with a large number of cues induces extinction learning, in which the cue loses its ability to elicit defensive responses (Myers and Davis 2007). There is ample evidence that plasticity important for extinction occurs in the basolateral amygdala (BLA; which includes the LA), though it is unclear exactly how this relates to the original memory trace in the dorsal LA (Bouton et al. 2021). For instance, consolidation of extinction is impaired by pretraining systemic inhibition of protein synthesis (Suzuki et al. 2004) and by pretraining inhibition of protein synthesis or ERK/MAPK in the BLA (Lin et al. 2003c; Herry et al. 2006). However, the Lin et al. (2003c) study measured the effects of protein synthesis inhibition in the BLA 30 min after extinction training, which is typically thought to reflect short-term memory. Subsequent work by another group found that postextinction training inhibition of protein synthesis impaired reconsolidation, making it difficult to assess the effects on extinction consolidation (Duvarci et al. 2006). There are also ongoing debates about the relative contribution of “erasure” versus “new learning” processes in extinction. Evidence that protein synthesis-dependent depotentiation of CS inputs to the LA contributes to extinction suggests up-regulation of polyribosomes in the LA pyramidal cells storing the original trace (Lin et al. 2003a,b,c; Kim et al. 2009). However, up-regulation of polyribosomes is also possible if extinction plasticity occurs in other cells or regions of the brain, as repeated retrieval trials may strongly trigger reconsolidation processes. Complicating things further, it appears that extinction can halt reconsolidation (Suzuki et al. 2004).To investigate the dynamics of local translation in the context of an established memory, we used ssTEM to quantify dendritic polyribosome distribution in the LA during the long-term memory phase of Pavlovian conditioning, reconsolidation, and consolidation of extinction. We hypothesized that polyribosomes would not be up-regulated in the long-term memory condition relative to controls, since memory maintenance is resistant to protein synthesis inhibition at this time point. We also hypothesized that both retrieval and extinction would induce up-regulation of polyribosomes, but in different patterns; for example, reconsolidation processes could be reflected in polyribosomes near large synapses, but extinction could result in loss of these synapses and perhaps more generalized polyribosome distribution.     

即刻消退缺损的原因分析及其神经生物学机制

即刻消退缺损(immediate extinction deficit, IED)是指在条件性恐惧习得后, 立即进行的消退训练不能长期抑制恐惧记忆的现象。IED可能与消退起始时的应激水平和事件分割等因素有关。在高应激水平下, 消退记忆的巩固受损导致IED; 而在中等或较低的应激水平条件下, 即刻消退有效但效果可能容易受事件分割的影响。IED的神经生物学机制涉及应激激活蓝斑去甲肾上腺素能系统, 去甲肾上腺素引起杏仁核基底外侧核(basolateral amygdala, BLA)过度兴奋, 然后BLA通过投射突触抑制在恐惧消退中起核心作用的内侧前额叶神经元的活动。未来研究应注意即刻消退缺损引起的长期后果, 并深入探讨如何优化即刻消退在临床上的应用。     

Effects of extinction in multiple contexts on the renewal of associative tolerance to ethanol

The Pavlovian analysis of drug tolerance describes how the contexts of drug administration participate in the elicitation of compensatory conditioned responses that are, at least partly, responsible for tolerance. Findings indicate that if an association is acquired in one context and extinguished in another one, when exposing the subjects to the acquisition context, renewal of the conditioned response will take place. Ambiguous evidence exists about whether or not this effect diminishes when extinguishing the association in multiple contexts. This investigation evaluates the existence of the phenomenon of renewal of tolerance to ethanol, and whether it diminishes by the extinction in multiple contexts. Evidence of renewal of tolerance to ethanol in rats was found, but no diminution was observed when extinguishing in multiple contexts.     

Activation and role of the medial prefrontal cortex (mPFC) in extinction of ethanol-induced associative learning in mice

Although the medial prefrontal cortex (mPFC) has been shown to be integrally involved in extinction of a number of associative behaviors, its role in extinction of alcohol (ethanol)-induced associative learning has received little attention. Previous reports have provided evidence supporting a role for the mPFC in acquisition and extinction of amphetamine-induced conditioned place preference (CPP) in rats, however, it remains unknown if this region is necessary for extinction of ethanol (EtOH)-induced associative learning in mice. Using immunohistochemical analysis of phosphorylated and unphosphorylated cAMP response element-binding protein (CREB), the current set of experiments first showed that the prelimbic (PL) and infralimbic (IL) subregions of the mPFC exhibited dynamic responses in phosphorylation of CREB to a Pavlovian-conditioned, EtOH-paired cue. Interestingly, CREB phosphorylation within these regions was sensitive to manipulations of the EtOH-cue contingency-that is, the cue-induced increase of pCREB in both the PL and IL was absent following extinction. In order to confirm a functional role of the mPFC in regulating the extinction process, we then showed that electrolytic lesions of the mPFC following acquisition blocked subsequent extinction of EtOH-CPP. Together, these experiments indicate a role for the PL and IL subregions of the mPFC in processing changes of the EtOH-cue contingency, as well as in regulating extinction of EtOH-induced associative learning in mice.     

Mediated configural learning in rats

Three experiments investigated mediated configural learning in male rats. In Experiment 1, after exposure to audio-visual compounds AX and BY, rats received trials where X was paired with shock, and Y was not. The idea that conditioning with X enables the evoked configural representation of AX to be linked to shock received support from the facts that while AX provoked more fear than BX, there was no difference between BY and AY. Similarly, Experiment 2 showed that after exposure to AX and BY, separate pairings of X and Y with shock resulted in more fear to AX and BY than AY and BX. In Experiment 3, rats in group consistent received separate exposures to A and X in Context C, and B and Y in D, while those in group inconsistent received A and X (and B and Y) in both C and D. After rats had received shocks in both C and D, rats in group consistent showed more fear to AX and BY than to BX and AY, but this was not the case in group inconsistent. These results indicate that configural representations, formed either by presenting auditory and visual stimuli as parts of a compound or in a shared context, are subject to a process of mediated learning.     

S-R associations, their extinction, and recovery in an animal model of anxiety: a new associative account of phobias without recall of original trauma

Associative accounts of the etiology of phobias have been criticized because of numerous cases of phobias in which the client does not remember a relevant traumatic event (i.e., Pavlovian conditioning trial), instructions, or vicarious experience with the phobic object. In three lick suppression experiments with rats as subjects, we modeled an associative account of such fears. Experiment 1 assessed stimulus-response (S-R) associations in first-order fear conditioning. After behaviorally complete devaluation of the unconditioned stimulus, the target stimulus still produced strong conditioned responses, suggesting that an S-R association had been formed and that this association was not significantly affected when the outcome was devalued through unsignaled presentations of the unconditioned stimulus. Experiments 2 and 3 examined extinction and recovery of S-R associations. Experiment 2 showed that extinguished S-R associations returned when testing occurred outside of the extinction context (i.e., renewal) and Experiment 3 found that a long delay between extinction and testing also produced a return of the extinguished S-R associations (i.e., spontaneous recovery). These experiments suggest that fears for which people cannot recall a cause are explicable in an associative framework, and indicate that those fears are susceptible to relapse after extinction treatment just like stimulus-outcome (S-O) associations.     

Using variability to guide dimensional weighting: associative mechanisms in early word learning

At 14 months, children appear to struggle to apply their fairly well-developed speech perception abilities to learning similar sounding words (e.g., bih/dih; Stager & Werker, 1997). However, variability in nonphonetic aspects of the training stimuli seems to aid word learning at this age. Extant theories of early word learning cannot account for this benefit of variability. We offer a simple explanation for this range of effects based on associative learning. Simulations suggest that if infants encode both noncontrastive information (e.g., cues to speaker voice) and meaningful linguistic cues (e.g., place of articulation or voicing), then associative learning mechanisms predict these variability effects in early word learning. Crucially, this means that despite the importance of task variables in predicting performance, this body of work shows that phonological categories are still developing at this age, and that the structure of noninformative cues has critical influences on word learning abilities.     

Brain mechanisms of extinction of the classically conditioned eyeblink response

It is well established that the cerebellum and its associated circuitry are essential for classical conditioning of the eyeblink response and other discrete motor responses (e.g., limb flexion, head turn, etc.) learned with an aversive unconditioned stimulus (US). However, brain mechanisms underlying extinction of these responses are still relatively unclear. Behavioral studies have demonstrated extinction as an active learning process distinct from acquisition. Experimental data in eyeblink conditioning suggest that plastic changes specific to extinction may play an important role in this process. Both cerebellar and hippocampal systems may be involved in extinction of these memories. The nature of this phenomenon and identification of the neural substrates necessary for extinction of originally learned responses is the topic of this review.     

Attentional mechanisms in visual signal detection: the effects of simultaneous and delayed noise and pattern masks

The attentional cuing effects in detection and some discrimination tasks depend on the use of backward masks and on the presence of external noise in the display. These effects have been attributed to an interruption masking mechanism, which terminates stimulus processing prematurely, and an external noise exclusion mechanism, which minimizes the perceptual effects of noise. To test whether the dependencies on masking and external noise are expressions of a single mechanism, observers detected grating patch stimuli, masked with noise masks or pattern masks, presented either simultaneously or after a delay of 60-90 msec. Contrary to an external noise exclusion account, but consistent with an interruption masking account, cuing effects were largest when the masks were delayed. However, weaker cuing effects were obtained with simultaneous masks, contrary to an interruption masking account. These results suggest that attentional effects in simple visual judgments are affected by mechanisms of both kinds.     

Perceptual specialization and configural face processing in infancy

Adults’ face processing expertise includes sensitivity to second-order configural information (spatial relations among features such as distance between eyes). Prior research indicates that infants process this information in female faces. In the current experiments, 9-month-olds discriminated spacing changes in upright human male and monkey faces but not in inverted faces. However, they failed to process matching changes in upright house stimuli. A similar pattern of performance was exhibited by 5-month-olds. Thus, 5- and 9-month-olds exhibited specialization by processing configural information in upright primate faces but not in houses or inverted faces. This finding suggests that, even early in life, infants treat faces in a special manner by responding to changes in configural information more readily in faces than in non-face stimuli. However, previously reported differences in infants’ processing of human versus monkey faces at 9 months of age (but not at younger ages), which have been associated with perceptual narrowing, were not evident in the current study. Thus, perceptual narrowing is not absolute in the sense of loss of the ability to process information from other species’ faces at older ages.     

Attentional focus, processing load, and Stroop interference

Although the effects of attentional focus and perceptual load on selective attention when targets and distractors are distinct objects that occupy separate locations are well known, there has been little examination of their role when both relevant and irrelevant information pertains to the same object. In four experiments, participants were shown Stroop color words or strings of letters in a task of speeded color identification. When the participants' attentional focus was manipulated via cue validity or precue size, greater Stroop interference was observed when the attentional focus was narrow than when it was broad. However, when the participants were induced to adopt a comparable attentional focus in a dual-task paradigm, the differential Stroop interference was eliminated. Furthermore, contrary to the prediction of the perceptual load hypothesis, different levels of processing load did not lead to differential Stroop interference. These results emphasize the importance of stimulus structure in understanding distractor processing. They indicate that when relevant and irrelevant information pertains to the same object, narrowing attentional focus increases distractor processing, and perceptual load has a negligible effect on the extent of distractor processing.     

Attentional Overload,stress, and simulate Driving Performance

This study tests the hypothesis that driver stress is associated with performance impairment because stress-prone drivers are vulnerable to overload of attentional resources. Eighty young-adult subjects performed a simulated drive concurrently with a grammatical reasoning task, presented either visually or auditorily. Priority assigned to the 2 tasks was also manipulated. In general, the patterns of dual-task interference predicted by attentional resource theory were not found, although interference was apparent with the auditory reasoning task. Measures of vulnerability to driver stress and intrusive cognitions were related to impaired lateral control mainly when task demands were relatively low, contrary to the overload hypothesis. These data indicate that performance in this task paradigm is characterized by adaptive mobilization of effort to meet changing task demands. Stressed drivers adapted to high levels of demand fairly efficiently, but they may be at risk of performance impairment when the task requires relatively little active control. Advantages and disadvantages of the simulator approach are discussed.     

Evidence for Distinct Attentional Bottlenecks in Attention Switching and Attentional Blink Tasks

E. Weichselgartner and G. A. Sperling (1987), using rapid serial visual presentation (RSVP), estimated that attention could be moved to a new spatial location within 300-400 ms. H. J. Müller and P. M. Rabbit (1989) used a spatial cuing task and found a similar time course for voluntarily redeploying attention. A separate phenomenon known as the attentional blink (AB) also follows a similar time course, yet occurs when participants attend to a single spatial location. The present study found that attention can be shifted more quickly than previously estimated and that part of the deficit observed during searches of spatially distinct RSVP streams is due to an AB. The results support some early and late selection accounts for the temporal dynamics of visual attention and suggest different bottlenecks during visual selection. The implications for visual search and visual processing are discussed.