Associative structure of differential inhibition: implications for models of conditioned inhibition

Following A+/X- training (with A, X, and + being a light, tone, and footshock, respectively), rats received extinction of A and the training context, extinction of the training context alone, or no extinction. The inhibitory potential of X was then assessed with conditioned lick suppression in a neutral context using both summation and retardation tests. Extinction of the training context alone and extinction of A and the training context reduced the inhibitory potential of X appreciably and equally. Hence, what is traditionally called differential inhibition appears to depend not on the excitatory value of A but on the excitatory value of the training context. In conjunction with what is known about other inhibitory training procedures, these results suggest that a conditioned inhibitor is a stimulus that has been paired with little or no reinforcement in the presence of an accompanying stimulus that predicts greater reinforcement.     

Contextual Pavlovian conditioning in the crab Chasmagnathus

In contextual conditioning, a complex pattern of information is processed to associate the characteristics of a particular place with incentive or aversive reinforcements. This type of learning has been widely studied in mammals, but studies of other taxa are scarce. The context-signal memory (CSM) paradigm of the crab Chasmagnathus has been extensively used as a model of learning and memory. Although initially interpreted as habituation, some characteristics of contextual conditioning have been described. However, no anticipatory response has been detected for animals exposed to the training context. Thus, CSM could be interpreted either as an associative habituation or as contextual conditioning that occurs without a context-evoked anticipatory response. Here, we describe a training protocol developed for contextual Pavlovian conditioning (CPC). For each training trial, the context (conditioned stimulus, CS) was discretely presented and finished together with the unconditioned stimulus (US). In agreement with the CSM paradigm, a robust freezing response was acquired during the 15 training trials, and clear retention was found when tested with the US presentation after short (2 and 4 h) and long (1–4 days) delays. This CPC memory showed forward but not simultaneous presentation conditioning and was context specific and protein synthesis dependent. Additionally, a weak CPC memory was enhanced during consolidation. One day after training, CPC was extinguished by repeated CS presentation, while one presentation induced a memory labilisation–reconsolidation process. Finally, we found an anticipatory conditioned response (CR) during the CS presentation for both short-term (4 h) and long-term memory (24 h). These findings support the conditioning nature of the new paradigm.     

Mismatch between what is expected and what actually occurs triggers memory reconsolidation or extinction

In previous experiments on contextual memory, we proposed that the unreinforced re-exposure to the learning context (conditioned stimulus, CS) acts as a switch guiding the memory course toward reconsolidation or extinction, depending on reminder duration. This proposal implies that the system computes the total exposure time to the context, from CS onset to CS offset, and therefore, that the reminder presentation must be terminated for the switching mechanism to become operative. Here we investigated to what extent this requirement is necessary, and we explored the relation between diverse phases in the reconsolidation and extinction processes. We used the contextual memory model of the crab Chasmagnathus which involves an association between the learning context (CS) and a visual danger stimulus (unconditioned stimulus, US). Administration of cycloheximide was used to test the lability state of memory at different time points. The results show that two factors, no-reinforcement during the reminder (i.e., CS re-exposure) and CS offset are the necessary conditions for both processes to occur. Regardless of the reminder duration, memory retrieved by unreinforced CS re-exposure emerges intact and consolidated when tested before CS offset, suggesting that neither reconsolidation nor extinction is concomitant with CS re-exposure. Either process could only be triggered once the definitive mismatch between CS and US is confirmed by CS termination without the expected reinforcement.     

The role of contextual associations in producing the partial reinforcement acquisition deficit

Three conditioned suppression experiments with rats as subjects assessed the contributions of the conditioned stimulus (CS)-context and context-unconditioned stimulus (US) associations to the degraded stimulus control by the CS that is observed following partial reinforcement relative to continuous reinforcement training. In Experiment 1, posttraining associative deflation (i.e., extinction) of the training context after partial reinforcement restored responding to a level comparable to the one produced by continuous reinforcement. In Experiment 2, posttraining associative inflation of the context (achieved by administering unsignaled outcome presentations in the context) enhanced the detrimental effect of partial reinforcement. Experiment 3 found that the training context must be an effective competitor to produce the partial reinforcement acquisition deficit. When the context was down-modulated, the target regained behavioral control thereby demonstrating higher-order retrospective revaluation. The results are discussed in terms of retrospective revaluation, and are used to contrast the predictions of a performance-focused model with those of an acquisition-focused model.     

Intolerance of uncertainty and novelty facilitated extinction: The impact of reinforcement schedule

Individuals who score high in intolerance of uncertainty (IU) display reduced threat extinction. Recently, it was shown that replacing threat associations with novel associations during extinction learning (i.e., presenting a novel tone 100% of the time) can promote threat extinction retention in individuals with high IU. This novelty facilitated extinction (NFE) effect could be driven by the tone's novelty or reliability. Here, we sought to address this question by adjusting the reliability of the novel tone (i.e., the reinforcement rate) during NFE. We measured skin conductance response during an associative learning task in which participants (n = 92) were assigned to one of three experimental groups: standard extinction, NFE 100% reinforcement, or NFE 50% reinforcement. For standard extinction, compared to NFE 100% and 50% reinforcement groups, we observed a trend for greater recovery of the conditioned response during extinction retention. Individuals with high IU relative to low IU in the standard extinction group demonstrated a larger recovery of the conditioned response during extinction retention. These findings tentatively suggest that NFE effects are driven by the novelty rather than the reliability of the new stimulus. The implications of these findings for translational and clinical research in anxiety disorder pathology are discussed.     

Survival of the partial reinforcement extinction effect after contextual shifts

The effects of contextual shifts on the partial reinforcement extinction effect (PREE) were studied in autoshaping with rats. Experiment 1 established that the two contexts used subsequently were easily discriminable and equally salient. In Experiment 2, independent groups of rats received acquisition training under partial reinforcement (PRF) or continuous reinforcement (CRF). Significant PREEs were observed whether extinction occurred in the same or in a different context. In Experiment 3, after PRF or CRF acquisition training, each group received extinction of the same conditioned stimulus in both the same and different contexts. PREEs were observed under both conditions, although extinction was accelerated after a contextual shift. These results were discussed in relation to the role of mediational states in the PREE.     

Adrenergic transmission facilitates extinction of conditional fear in mice

Extinction of classically conditioned fear, like its acquisition, is active learning, but little is known about its molecular mechanisms. We recently reported that temporal massing of conditional stimulus (CS) presentations improves extinction memory acquisition, and suggested that temporal spacing was less effective because individual CS exposures trigger two opposing processes: (1) fear extinction, which is favored by CS massing, and (2) fear incubation (increase), which is favored by spacing. We here report the effects of manipulating the adrenergic system during massed or spaced CS presentations in fear-conditioned mice. We administered yohimbine (5 mg/kg), an alpha(2)-receptor antagonist, or propranolol (10 mg/kg), a beta-receptor antagonist, systemically prior to CS presentation sessions and recorded both short- and long-term changes in conditional freezing. Yohimbine treatment facilitated extinction of both cue and context fear with massed protocols. When given before spaced CS presentations, propranolol led to a persistent incubation of cue fear, whereas yohimbine led to persistent extinction, compared with vehicle-treated animals, which showed no change in fear. These results suggest that norepinephrine positively modulates the formation of fear extinction memories in mice. They also provide clear evidence that spaced CS presentations trigger both fear-reducing (extinction) and fear-increasing (incubation) mechanisms.     

条件性恐惧记忆消退返回的性别差异

采用预期判断任务考察男女性对已消退的条件性恐惧记忆是否会出现消退返回的现象。结果表明: (1)在对已习得的条件性恐惧记忆消退后4个小时进行测试, 被试整体会出现明显的消退返回现象; (2)对消退返回现象的性别差异进行比较, 女性比男性的消退返回现象更突出, 并且差异显著; (3)与男性相比, 女性对条件性恐惧记忆具有易习得难消退的趋势, 但是性别差异不显著。研究结果验证了消退返回现象存在的普遍性, 并且有着显著的性别差异, 为以后对创伤后应激障碍患者的治疗应考虑性别因素提供了心理学依据。     

Extinction of goal tracking also eliminates the conditioned reinforcing effects of an appetitive conditioned stimulus

Previous studies have suggested that the effects of extinction are response-specific. The present study investigated whether an extinction treatment that eliminated goal tracking elicited by an appetitive conditioned stimulus (CS) would also eliminate the conditioned reinforcing effects of that CS. Rats were first trained on a goal-tracking procedure in which an auditory CS was paired with a food unconditioned stimulus. Animals learned to approach the location where the food was delivered. In a subsequent phase, rats in one group received extinction training that eliminated the goal-tracking elicited by the CS. Rats in the other group did not experience extinction of the food-paired CS. Then, both groups received a test for conditioned reinforcement in which leverpresses resulted in the brief presentation of the stimulus previously paired with food. This stimulus did not act as a conditioned reinforcer in the group that had been subjected to extinction training, but did serve as a conditioned reinforcer in the group that did not experience extinction. These results indicate that the effects of extinction generalize from the approach-eliciting to the conditioned reinforcing effects of an appetitive CS.     

Interaction between the basolateral amygdala and dorsal hippocampus is critical for cocaine memory reconsolidation and subsequent drug context-induced cocaine-seeking behavior in rats

Contextual stimulus control over instrumental drug-seeking behavior relies on the reconsolidation of context-response-drug associative memories into long-term memory storage following retrieval-induced destabilization. According to previous studies, the basolateral amygdala (BLA) and dorsal hippocampus (DH) regulate cocaine-related memory reconsolidation; however, it is not known whether these brain regions interact or independently control this phenomenon. To investigate this question, rats were trained to lever press for cocaine reinforcement in a distinct environmental context followed by extinction training in a different context. Rats were then briefly re-exposed to the cocaine-paired context to destabilize cocaine-related memories, or they were exposed to an unpaired context. Immediately thereafter, the rats received unilateral microinfusions of anisomycin (ANI) into the BLA plus baclofen/muscimol (B/M) into the contralateral (BLA/DH disconnection) or ipsilateral DH, or they received contralateral or ipsilateral microinfusions of vehicle. They then remained in their home cages overnight or for 21 d, followed by additional extinction training and a test of cocaine-seeking behavior (nonreinforced active lever responding). BLA/DH disconnection following re-exposure to the cocaine-paired context, but not the unpaired context, impaired subsequent drug context-induced cocaine-seeking behavior relative to vehicle or ipsilateral ANI + B/M treatment. Prolonged home cage stay elicited a time-dependent increase, or incubation, of drug-context-induced cocaine-seeking behavior, and BLA/DH disconnection inhibited this incubation effect despite some recovery of cocaine-seeking behavior. Thus, the BLA and DH interact to regulate the reconsolidation of cocaine-related associative memories, thereby facilitating the ability of drug-paired contexts to trigger cocaine-seeking behavior and contributing to the incubation of cocaine-seeking behavior.     

The effects of context extinction on US signal value

Two experiments with rats examined the effects of context extinction on responding to the signal value of an unconditioned stimulus (US). In Experiment 1, US signal value was first trained when a single food pellet signaled the delivery of three additional pellets. After training, rats received either context extinction (CE) or home cage (HC) exposure before testing US signal value by single food pellet presentations. Results showed responding was significantly reduced in Group CE compared to Group HC. Experiment 2 replicated Experiment 1 and showed that exposure to a different context did not reduce responding to the signal value of a US. The results complement research by Kehoe et al. [Kehoe, E. J., Weidemann, G., & Dartnall, S. (2004). Apparatus exposure produces profound declines in conditioned nictitating-membrane responses to discrete conditioned stimuli by the rabbit (Oryctolagus cuniculus). Journal of Experimental Psychology: Animal Behavior Processes, 30, 259–270.] and have key implications for prominent theories of conditioning.     

Differential roles for hippocampal areas CA1 and CA3 in the contextual encoding and retrieval of extinguished fear

Recent studies demonstrate that context-specific memory retrieval after extinction requires the hippocampus. However, the contribution of hippocampal subfields to the context-dependent expression of extinction is not known. In the present experiments, we examined the roles of areas CA1 and CA3 of the dorsal hippocampus in the context specificity of extinction. After pairing an auditory conditional stimulus (CS) with an aversive footshock (unconditional stimulus or US), rats received extinction sessions in which the CS was presented without the US. In Experiment 1, pretraining neurotoxic lesions in either CA1 or CA3 eliminated the context dependence of extinguished fear. In Experiment 2, lesions of CA1 or CA3 were made after extinction training. In this case, only CA1 lesions impaired the context dependence of extinction. Collectively, these results reveal that both hippocampal areas CA1 and CA3 contribute to the acquisition of context-dependent extinction, but that only area CA1 is required for contextual memory retrieval.     

Assessing the role of alternative response rates and reinforcer rates in resistance to extinction of target responding when combining stimuli

Studies of behavioral momentum reveal that reinforcing an alternative response in the presence of a target response reduces the rate of target responding but increases its persistence, relative to training the target response on its own. Because of the parallels between these studies and differential‐reinforcement techniques to reduce problem behavior in clinical settings, alternative techniques to reduce problem behavior without enhancing its persistence are being explored. One potential solution is to train an alternative response in a separate stimulus context from problem behavior before combining the alternative stimulus with the target stimulus. The present study assessed how differences in reinforcement contingencies and rate for alternative responding influenced resistance to extinction of target responding when combining alternative and target stimuli in pigeons. Across three experiments, alternative stimuli signaling a response–reinforcer dependency and greater reinforcer rates more effectively decreased the persistence of target responding when combining alternative and target stimuli within the same extinction tests, but not when compared across separate extinction tests. Overall, these findings reveal that differences in competition between alternative and target responding produced by contingencies of alternative reinforcement could influence the effectiveness of treating problem behavior through combining stimulus contexts.     

RESISTANCE TO EXTINCTION AND RELAPSE IN COMBINED STIMULUS CONTEXTS

Reinforcing an alternative response in the same context as a target response reduces the rate of occurrence but increases the persistence of that target response. Applied researchers who use such techniques to decrease the rate of a target problem behavior risk inadvertently increasing the persistence of the same problem behavior. Behavioral momentum theory asserts that the increased persistence is a function of the alternative reinforcement enhancing the Pavlovian relation between the target stimulus context and reinforcement. A method showing promise for reducing the persistence‐enhancing effects of alternative reinforcement is to train the alternative response in a separate stimulus context before combining with the target stimulus in extinction. The present study replicated previous findings using pigeons by showing that combining an “alternative” richer VI schedule (96 reinforcers/ hr) with a “target” leaner VI schedule (24 reinforcers/hr) reduced resistance to extinction of target responding compared with concurrent training of the alternative and target responses (totaling 120 reinforcers/hr). We also found less relapse with a reinstatement procedure following extinction with separate‐context training, supporting previous findings that training conditions similarly influence both resistance to extinction and relapse. Finally, combining the alternative stimulus context was less disruptive to target responding previously trained in the concurrent schedule, relative to combining with the target response trained alone. Overall, the present findings suggest the technique of combining stimulus contexts associated with alternative responses with those associated with target responses disrupts target responding. Furthermore, the effectiveness of this disruption is a function of training context of reinforcement for target responding, consistent with assertions of behavioral momentum theory.     

The effects of physical context changes and multiple extinction contexts on two forms of renewal in a conditioned suppression task with humans

Three experiments examined the effects of physical context changes and multiple extinction contexts on the renewal of conditioned suppression in humans. A conditioned suppression task used an undesirable event as the unconditional stimulus (US). One conditional stimulus (CS+) predicted the occurrence of the US and another (CS−) predicted US absence. In Experiment 1 (N = 32), conditioned suppression was acquired to the CS+ in one context and extinguished in a different context. An increase in suppression was found for the CS+ and not for the CS− when subsequent test trials were conducted in the acquisition context (ABA renewal). Experiment 2 (N = 32) tested for ABC Renewal and showed increased suppression to both the CS+ and CS− when test was conducted in a novel context. Experiment 3 (N = 80) showed that these two effects were abolished when extinction was conducted in multiple contexts. The experiments extend the ABA renewal of conditioned suppression found with non-human animal subjects and the reduction of renewal by extinction in multiple contexts. Context changes may also facilitate cue competition effects after training with elementary stimuli, as shown by the effects of US omission in the ABA and ABC renewal groups.     

Contextual control of negative transfer produced by prior CS-US pairings

When a conditioned stimulus (CS) is repeatedly paired with a weak unconditioned stimulus (US) prior to being paired with a stronger US in a second conditioning phase, interference, or negative transfer, is often observed during Phase 2. Two conditioned suppression experiments with rat subjects examined the effect of a context switch between phases in this “Hall-Pearce negative transfer paradigm.” In Experiment 1, negative transfer was obtained when the context remained the same for both phases, but there was no evidence of negative transfer when the context was switched between phases. Experiment 2 was designed to control for familiarity with the Phase 2 context, and showed that a context switch between phases again attenuated negative transfer. The effect of context on negative transfer was also similar to its effect on latent inhibition produced under comparable conditions. The results are not consistent with a model proposed by J. M. Pearce and G. Hall (Psychological Review, 87, 532–555, 1980), which ascribes no major role to the context in this situation, but are consistent with A. R. Wagner's (In S. H. Hulse, H. Fowler, & W. K. Honig, Eds., Cognitive Processes in Animal Behavior, pp. 177–209. Hillsdale NJ: Erlbaum, 1978) short-term memory model of conditioning, or with the view that contexts may signal specific CS-US relations. The results extend previous research on other interference paradigms, like latent inhibition and extinction, where context may play a similar role.     

Occasional reinforced trials during extinction can slow the rate of rapid reacquisition

Two appetitive conditioning experiments with rats examined reacquisition after conditioned responding was eliminated by either extinction or by a partial reinforcement procedure in which reinforced trials were occasionally presented among many nonreinforced trials. In Experiment 1, reacquisition to a conditional stimulus (CS) that had been conditioned and extinguished was more rapid than acquisition in a group that had received no prior conditioning. However, the addition of occasional reinforced trials to extinction slowed this rapid reacquisition effect. Experiment 2 replicated the result and showed that a procedure in which the CS and the unconditional stimulus (US) were unpaired in extinction interfered even further with reacquisition. The results suggest that rapid reacquisition is ordinarily produced when reinforced trials provide a contextual cue that can renew responding by signaling other acquisition trials (Ricker & Bouton, 1996). The effects of partial reinforcement in extinction are surprising from several theoretical perspectives and have useful clinical implications.     

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.     

Conditioned suppression of an avoidance response by a stimulus paired with food

Three food-deprived Long-Evans rats were exposed to a non-discriminated shock avoidance procedure. Superimposed upon this operant avoidance baseline were periodic presentations of a conditioned stimulus that was paired with food, the unconditioned stimulus. These pairings resulted in increases in the rate of shock over that recorded when the conditioned stimulus was not present. A traditional suppression ratio failed to reveal any differential effect of the conditioned stimulus on the overall rate of avoidance responding, although all subjects showed a consistent pattern of pausing and postshock response bursts during presentations of the conditioned stimulus. When food was withheld during a final extinction phase, the conditioned stimulus ceased to occasion increases in shock rates and disruptive postshock response bursts were eliminated. An analysis of conditioned suppression procedures is proposed that stresses not only operant-Pavlovian or appetitive-aversive incompatibility, but also the manner in which the baseline schedule of reinforcement affects operant behavior changes that are elicited by the superimposed Pavlovian procedure.