"The effects of neurotoxic hippocampal lesions on two effects of context after fear extinction": Errata.

Reports an error in the original article by R. J. Frohardt et al (Behavioral Neuroscience, 2000 [Apr], Vol 114[2], 227-240). On page 229, there is an error in the Method section. The second full sentence on that page should read: Neurotoxic lesions of hippocampus were produced by injections of a mixture of 5.0 μg ibotenic acid and 5.0 μg NMDA per 0.5 ml of normal saline. (The following abstract of this article originally appeared in record 2000-15286-001): Three conditioned suppression experiments with rats examined the role of the hippocampus in 2 effects of context after extinction. Reinstatement is the context-specific recovery of fear to an extinguished conditioned stimulus (CS) that occurs following independent presentations of the unconditioned stimulus (UCS), after extinction. Renewal is the recovery of fear when the CS is presented in the context in which it was conditioned, after extinction in a different context. Results indicated that neurotoxic lesions of the hippocampus, performed before conditioning, abolished reinstatement, which depends on context-UCS associations, but not renewal, which does not. This dissociation is not the result of differences in the recentness of context learning that ordinarily governs the two effects… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of the rat hippocampal system in several effects of context in extinction.

The effect of fornix lesions on some effects of manipulating the context on performance in extinction were studied. In renewal, subjects' responding to an extinguished CS recovered when the CS was presented in the context in which it had been conditioned after extinction in a different context. In reinstatement, it recovered when the CS was tested after independent presentation of the unconditioned stimulus (UCS; an effect mediated by contextual conditioning.) In spontaneous recovery, it recovered after the passage of time, that is, when the CS was tested in a new temporal context. In the conditioned suppression method, fornix lesions had no effect on conditioning, extinction, renewal, or spontaneous recovery; however, they abolished the reinstatement effect. The results suggest that the hippocampal system may be important in the formation of context–UCS associations, but not in other types of learning about the context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned stimulus familiarity determines effects of MK-801 on fear extinction.

Six experiments studied the role of conditioned stimulus (CS) familiarity in determining the effects of the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 on fear extinction. Systemic administration of MK-801 (0.1 mg/kg) impaired initial extinction but not reextinction learning. MK-801 impaired reextinction learning when the CS was relatively novel during reextinction training but not initial extinction learning when the CS was relatively familiar during initial extinction training. A context change failed to reinstate the sensitivity of initial fear extinction learning about a relatively familiar CS to MK-801. These experiments show that CS familiarity is an important determinant of effects of MK-801 on fear extinction learning: MK-801 impaired extinction learning about novel stimuli but spared extinction learning about familiar stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of context on performance to conditioned stimuli with mixed histories of reinforcement and nonreinforcement.

Five conditioned suppression experiments, with 160 Wistar rats, explored the role of the conditioning history of the conditioned stimulus (CS) in determining the effects of contextual fear on performance to the CS. Contextual fear was produced by postconditioning exposure to unconditioned stimulus/stimuli (UCS) alone in the context of conditioning; it was independently assessed with context-preference tests. When the number of reinforced and nonreinforced trials was equated across extinction, partial reinforcement, and latent inhibition procedures, only the extinction procedure produced a CS whose performance was subsequently affected (i.e., augmented) by contextual fear. Contextual fear's relatively unique augmenting effect on fear of an extinguished CS was abolished by extensive, but not by less extensive, reacquisition training. Results indicate that, depending on the CS's conditioning history, contextual fear either augments or has little effect on fear of the CS. It is suggested that augmentation by context should be viewed as the restoration of fear that is otherwise depressed by extinction. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Associative effects of US preexposure: Modulation of conditioned responding by an excitatory training context.

Conducted 2 experiments with 120 naive Sprague-Dawley rats to examine factors that contribute to retarded emergence of conditioned responding to a conditioned stimulus/stimuli (CS) trained in a context in which unsignaled unconditioned stimulus/stimuli (UCS) had previously been administered. In both experiments, water-deprived Ss were used in a conditioned lick suppression task to measure the conditioned response (CR) elicitation potential of the CS and the training context. From Exp I, it was determined that nonreinforced exposure to the excitatory context after UCS preexposure and prior to CS–UCS pairings in that context eliminated the CR deficit observed on a subsequent test of the CS. From Exp II, it was determined that the recovery induced by contextual deflation after CS training was specific to deflation of the context in which the CS was trained as opposed to another excitatory context. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Slow reacquisition following extinction: Context, encoding, and retrieval mechanisms.

Investigated the slow reacquisition (RAQ) of responding in rats that occurs when the conditioned stimulus/stimuli (CS) and unconditioned stimulus/stimuli (UCS) are paired again after prolonged extinction training. In Exp 1, an extinguished CS acquired less suppression than a novel CS during a final conditioning phase, but more suppression than CSs that had received comparable nonreinforcement without initial conditioning. In Exp 2, CS–UCS pairings resumed in the context of extinction caused the least RAQ of suppression: Pairings in a neutral context produced better RAQ, while return of the CS to the conditioning context caused an immediate renewal of responding to the CS. In Exp 3, a return of the CS to the extinction context after RAQ training caused renewed extinction performance and interfered with performance appropriate to RAQ. This effect was not due to demonstrable inhibitory conditioning of the extinction context. Results suggest that representations of conditioning and extinction (or CS–UCS and CS–no UCS relations) are both retained through extinction and that performance appropriate to either phase can be cued by the corresponding context. RAQ may thus be slow when the context retrieves an extinction memory. Similar mechanisms may also play a role in other Pavlovian interference paradigms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Observational fear conditioning in the acquisition and extinction of attentional bias for threat: An experimental evaluation.

Anxious persons show automatic and strategic attentional biases for threatening information. Yet, the mechanisms and processes that underlie such biases remain unclear. The central aim of the present study was to elucidate the relation between observational threat learning and the acquisition and extinction of biased threat processing by integrating emotional Stroop color naming tasks within an observational differential fear conditioning procedure. Forty-three healthy female participants underwent several consecutive observational fear conditioning phases. During acquisition, participants watched a confederate displaying mock panic attacks (UCS) paired with a verbal stimulus (CS+), but not with a second nonreinforced verbal stimulus (CS-). As expected, participants showed greater magnitude electrodermal and verbal-evaluative (e.g., distress, fear) conditioned responses to the CS+ over the CS- word. Participants also demonstrated slower color-naming latencies to CS+ compared to the CS- word following acquisition and showed attenuation of this preferential processing bias for threat following extinction. Findings are discussed broadly in the context of the interplay between fear learning and processing biases for threat as observed in persons suffering from anxiety disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential control by context in the inflation and reinstatement paradigms.

Examined, in 5 conditioned suppression experiments, the influence of summation between fear of the CS and the context in experimental paradigms in which the rat is exposed to UCSs following conditioning or extinction. Context-preference tests assessed contextual fear. In Exps I–III with 88 female Wistar rats, the inflation paradigm, in which fear of a CS paired with a weak UCS is enhanced by exposure to intense UCS alone, was investigated. Results show that the contextual fear that was present when the target CS was tested was reduced by presenting the intense UCSs in a different context, by exposing Ss to the context following their presentation, and by signaling the intense UCSs with a 2nd CS. In Exp IV with 32 female Wistar rats, UCS exposures following conditioning or extinction both produced contextual fear, but only fear of the extinguished CS was reinstated by that fear. In Exp V with 32 female Wistar rats, identical amounts of contextual fear reinstated fear of an extinguished CS, but not a nonextinguished CS, when the 2 types of CSs were arranged to evoke comparable amounts of fear prior to testing. It is suggested that contextual fear plays a role in the reinstatement paradigm but not in the inflation paradigm. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampectomy disrupts trace eye-blink conditioning in rabbits.

The role of the hippocampus (HPC) in trace eye-blink conditioning was evaluated using a 100-ms tone conditioned stimulus/stimuli (CS), a 300- or 500-ms trace interval, and a 150-ms air puff unconditioned stimulus/stimuli (UCS). Rabbits received complete hippocampectomy (dorsal & ventral), sham lesions or neocortical lesions. Hippocampectomy produced differential effects in relation to the trace interval used. With a 300-ms trace interval, HPC-lesioned Ss showed profound resistance to extinction after acquisition. With a 500-ms trace interval, HPC-lesioned Ss did not learn the task (only 22% conditioned responses [CRs] after 25 sessions, whereas controls showed >80% after 10 sessions), and on the few trials in which a CR occurred, most were "nonadaptive" short-latency CRs (i.e., they started during or just after the CS and always terminated prior to UCS onset). The authors conclude that the HPC encodes a temporal relationship between CS and UCS, and when the trace interval is long enough (e.g., 500 ms), that the HPC is necessary for associative learning of the conditioned eye-blink response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NMDA receptor antagonist MK-801 blocks learning of conditioned stimulus-unconditioned stimulus contiguity but not fear of conditioned stimulus in goldfish (Carassius auratus L.).

The blockade of learning of Pavlovian fear conditioning by the N-methyl-D-aspartic acid (NMDA)-receptor antagonist MK-801 was examined in 166 goldfish. In previously untrained fish, MK-801 blocked learning of a light-off or a tone conditioned stimulus (CS) paired with an electrical shock unconditioned stimulus (UCS). Pretraining on the light-off CS did not affect the rate of learning of the tone CS but protected the tone learning from disruption by MK-801. Switching from the light-off to the tone CS changed the identity of the CS but not its temporal contiguity with the UCS. Pretraining consisting of pseudoconditioning of the light-off CS did not protect subsequent tone learning from blockade by MK-801. Thus, the NMDA receptor functions are necessary for learning related to the temporal contiguity of the CS and UCS but not to the identity of the CS as a cue to the occurrence of the fearful effects of the UCS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid reacquisition in conditioning of the rabbit's nictitating membrane response.

Reacquisition after extinction often appears faster than original acquisition. However, data from conditioned suppression studies indicate that this effect may arise from spontaneous recovery and reinstatement of unextinguished contextual stimuli related to the unconditioned stimulus/stimuli (UCS). In the present experiments using the rabbit nictitating membrane preparation, spontaneous recovery was eradicated before reacquisition training. UCS contextual stimuli were controlled by retaining the UCS during extinction through explicit unpairings of the conditioned stimulus/stimuli (CS) and UCS. Attempts were also made to drive the associative strength of the CS into the inhibitory region by differential conditioning and conditioned inhibition procedures. In all cases, reacquisition was very rapid in comparison with a rest control. The results are discussed with respect to their implications for CS and UCS processing models of conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reevaluating evaluative conditioning: A nonassociative explanation of conditioning effects in the visual evaluative conditioning paradigm.

In 2 studies, the authors investigated whether evaluative conditioning (EC) is an associative phenomenon. Experiment 1 compared a standard EC paradigm with nonpaired and no-treatment control conditions. EC effects were obtained only when the conditioned stimulus (CS) and unconditioned stimulus (UCS) were rated as perceptually similar. However, similar EC effects were obtained in both control groups. An earlier failure to obtain EC effects was reanalyzed in Experiment 2. Conditioning-like effects were found when comparing a CS with the most perceptually similar UCSs used in the procedure but not when analyzing a CS rating with respect to the UCS with which it was paired during conditioning. The implications are that EC effects found in many studies are not due to associative learning and that the special characteristics of EC (conditioning without awareness and resistance to extinction) are probably nonassociative artifacts of the EC paradigm. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinstatement of Conditioned Fear in Humans Is Context Dependent and Impaired in Amnesia.

A contextual reinstatement procedure was developed to assess the contributions of environmental cues and hippocampal function in the recovery of conditioned fear following extinction in humans. Experiment 1 showed context specificity in the recovery of extinguished skin conductance responses after presentations of an auditory unconditioned stimulus. Experiment 2 demonstrated that fear recovery did not generalize to an explicitly unpaired conditioned stimulus. Experiment 3 replicated the context dependency of fear recovery with a shock as an unconditioned stimulus. Two amnesic patients failed to recover fear responses following reinstatement in the same context, despite showing initial fear acquisition. These results extend the known functions of the human hippocampus and highlight the importance of environmental contexts in regulating the expression of latent fear associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiation or diminution of discrete motor unconditioned responses (rabbit eyeblink) to an aversive Pavlovian unconditioned stimulus by two associative processes: Conditioned fear and a conditioned diminution of unconditioned stimulus processing.

In 2 experiments using the rabbit conditioned eyeblink preparation, the conditions under which a Pavlovian conditioned stimulus/stimuli (CS) potentiates or diminishes the unconditioned response (UCR) were examined. Results indicate that, after discrimination training (CS+ vs CS–), the CS+ diminished UCR amplitude at the training interstimulus interval (ISI). When CS+ trials were segregated into trials on which a conditioned response (CR) did or did not occur, the CS+ diminished the UCR when it elicited a CR, but not when a CR failed to occur. When the CS-unconditioned stimulus (UCS) interval was lengthened to 10 sec, the CS+ reliably potentiated the eyeblink UCR on CR trials but did not potentiate responding on trials on which a CR was absent. Results are discussed in terms of the modulatory effects and temporal properties of conditioned fear and an associatively produced decrement in UCS processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pavlovian conditioned inhibition.

Examined the notion of conditioned inhibition and suggests a definition in terms of the learned ability of a stimulus to control a response tendency opposed to excitation. 2 techniques of measuring inhibition are outlined: (1) the summation procedure in which an inhibitor reduces the response that would normally be elicited by another stimulus, and (2) the retardation of acquisition procedure in which an inhibitor is retarded in the acquisition of an excitatory CR. Examples of the use of these procedures are given for a variety of UCS modalities. Several possible operations for generating conditioned inhibitors are reviewed: extinction following excitatory conditioning, discriminative conditioning, arrangement of a negative correlation between CS and a UCS, use of an extended CS-UCS interval, and presentation of a stimulus in conjunction with UCS termination. These operations suggest that conditioned inhibitors are not generated either by simple extinction procedures or by pairing a stimulus with UCS termination. By contrast, for both salivary and fear conditioning the other procedures do appear to generate inhibitors. Most of the procedures generating conditioned inhibitors can be described as arranging a negatively correlated CS and UCS. (2 p. ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of yohimbine on the extinction of conditioned fear: A role for context.

Six experiments with rat subjects examined the effect of yohimbine, an alpha-2 adrenergic autoreceptor antagonist, on the extinction of conditioned fear to a tone. Experiments 1 and 2 demonstrated that systemic administration of yohimbine (1.0 mg/kg) facilitated a long-term decrease in freezing after extinction, and this depended on pairing drug administration with extinction training. However, Experiments 3 and 4 demonstrated that yohimbine did not eradicate the original fear learning: Freezing was renewed when the tone was tested outside of the extinction context. Experiments 5 and 6 found that the contextually specific attenuation of fear produced by yohimbine transferred to another extinguished conditional stimulus (CS) and not to a nonextinguished CS. The results suggest that yohimbine, when administered in the presence of a neutral context, creates a form of inhibition in that context that allows that specific context to reduce fear of an extinguished CS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analysis of the associative and occasion-setting properties of contexts participating in a Pavlovian discrimination.

In 3 conditioned suppression experiments with 64 male Wistar rats, contextual control of performance to a conditioned stimulus (CS) was generated by alternating CS–unconditioned stimulus (UCS) pairings in Context A with CS presentations alone in Context B. Suppression to the CS during discrimination training and during tests of the CS in a 3rd context suggested that Contexts A and B had both acquired an ability to modulate performance. Whether the contexts modulated behavior through their direct associations with the UCS or through their abilities to occasion-set the CS–UCS relation was explored. There was no evidence of direct context–UCS associations in either context. Repeated extinction exposures to Context A following discrimination training did not affect its ability to modulate CS performance. Excitatory conditioning of Context B, however, abolished its ability to modulate. It is suggested that demonstrable context–UCS associations are not necessary for the contextual control of CS performance and that although the parallel is not perfect, contexts share several critical properties with stimuli that occasion-set CS–UCS relations. The possible role of configural conditioning is discussed. (54 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat

The hippocampus is believed to be an important structure for learning tasks that require temporal processing of information. The trace classical conditioning paradigm requires temporal processing because the conditioned stimulus (CS) and the unconditioned stimulus (US) are temporally separated by an empty trace interval. The present study sought to determine whether the hippocampus was necessary for rats to perform a classical trace fear conditioning task in which each of 10 trials consisted of an auditory tone CS (1 5-s duration) followed by an empty 30-s trace interval and then a fear-producing floor-shock US (0.5-s duration). Several weeks prior to training, animals were anesthetized and given aspiration lesions of the neocortex (NEO; n = 6), hippocampus and overlying neocortex (HIPP; n = 7), or no lesions at all (control; n = 6). Approximately 24 h after trace conditioning, NEO and control animals showed a significant decrease in movement to a CS-alone presentation that was indicative of a conditioned fear response. Animals in the HIPP group did not show conditioned fear responses to the CS alone, nor did a pseudoconditioning group (n = 7) that was trained with unpaired CSs and USs. Furthermore, all groups except the HIPP group showed conditioned fear responses to the original context in which they received shock USs. One week later, HIPP, NEO, and control animals received delay fear-conditioning trials with no trace interval separating the CS and US. Six of seven HIPP animals could perform the delay version, but none could perform the trace version. This result suggests that the trace fear task is a reliable and useful model for examining the neural mechanisms of hippocampally dependent learning.     

Conditioning the unconditioned response: Modification of the rabbit's (Oryctolagus cuniculus) unconditioned nictitating membrane response.

Conditioning-specific reflex modification (CRM) occurs when classical conditioning modifies responding to a unconditioned stimulus/stimuli (UCS) in the absence of a conditioned stimulus (CS). Three experiments monitored rabbit (Oryctolagus cuniculus) nictitating membrane unconditioned responses to 5 intensities and 4 durations of periorbital electrical stimulation before and after CS or UCS manipulation. CRM occurred after 12 days of CS-UCS pairings but not following unpaired CS/UCS presentations or restraint. CRM survived CS-alone and CS/UCS-unpaired extinction of the conditioned response (CR) but not presentations of the UCS alone, although CRs remained intact. Thus, CRs could be weakened without eliminating CRM and CRM could be weakened without eliminating CRs. Data indicate CRM is a reliable, associative effect that is more than a generalized CR and may not be explained by habituation, stimulus generalization, contextual conditioning, or bidirectional conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The benzodiazepine midazolam does not impair Pavlovian fear conditioning but regulates when and where fear is expressed.

Rats were injected with a benzodiazepine (midazolam) and shocked after presentation of an auditory conditioned stimulus (CS). They were then tested for fear reactions (freezing) to the CS in either the original context or a 2nd context after either a short (1-day) or long (21-day) retention interval. Rats tested in the original context froze less after 1 day than rats tested after that interval in the 2nd context or rats tested after 21 days. Moreover, rats tested after the long interval in the original context froze less than rats tested after that interval in the 2nd context. Therefore, midazolam does not impair the acquisition of conditioned fear but regulates when and where that fear is expressed. These effects of midazolam were interpreted as a contextually controlled deficit in the expression of conditioned fear that is similar to that associated with latent inhibition and extinction (M. E. Bouton, 1993). (PsycINFO Database Record (c) 2010 APA, all rights reserved)