Postconditioning isolation disrupts contextual conditioning: an experimental analysis

Contextual-fear conditioning requires a lengthy retention period to fully emerge. This phenomenon might reflect the consolidation of a representation of the context that can be used to evoke fear. To investigate this hypothesis, 25 day-old rats that were returned to their home cages after conditioning were compared with rats that were isolated in a novel room. Isolation disrupted contextual but not auditory-cue fear conditioning when the conditioning-isolation interval was 2 hr or less, but not when it was 24 hr. Preexposure to the context prevented the isolation effect, and isolation disrupted this effect of context preexposure. These results support the consolidation hypothesis and the view that contextual- and auditory-cue fear conditioning depend on different processes.     

A selective role for corticosterone in contextual-fear conditioning.

The contribution of corticosterone to contextual- and auditory-cue fear conditioning was examined. Adrenalectomized rats showed reduced contextual-fear conditioning when tested 24 hr after conditioning; however, neither immediate contextual- nor auditory-cue fear conditioning was impaired. Contextual-fear conditioning in adrenalectomized rats with corticosterone replacement during the 4-day interval separating surgery and conditioning matched the level of controls. Moreover, rats exposed to the context prior to adrenalectomy showed normal long-term contextual-fear conditioning. Corticosterone replacement administered after the conditioning episode also negated the effects of adrenalectomy. Thus, corticosterone's role in fear conditioning is selective: It appears to contribute to the neural processes that support the consolidation of a long-term memory representation of the context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Familiarity-based stimulus generalization of conditioned suppression in rats is dependent on the perirhinal cortex.

We report that bilateral, excitoxic lesions of the perirhinal cortex attenuate rats' familiarity-based stimulus generalization. After surgery, rats were preexposed either to 2 auditory stimuli (A and B) or to only 1 auditory stimulus (B). Following preexposure, all rats received pairings of A and a footshock before assessment of generalized responding (conditioned suppression) to B. Sham rats' generalization was greater when preexposure was to both A and B than when preexposure was to B only. That pattern was abolished in lesioned rats, though no general deficiency was found in other measures of auditory processing. Our findings suggest that the perirhinal cortex is required for rats to encode familiarity as part of stimulus representations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conserved regulatory element involved in the early onset of Hoxb6 gene expression

When administered before training to 23-day-old Long-Evans rats, scopolamine hydrobromide significantly impaired both contextual and auditory-cue fear conditioning in a dose-dependent manner. Methylscopolamine which does not cross the blood-brain barrier, however, had no effect on either form of conditioned fear. Scopolamine administered up to 3 h after training also impaired both forms of fear conditioning when administered following a single pairing of the auditory cue and shock. When rats received three pairings, however, a posttraining treatment with scopolamine only impaired contextual fear conditioning. These results suggest that central cholinergic systems are involved in the posttrial processes that establish the memory trace for the conditioning experience.     

The effects of FG7142 on two types of forgetting in 18-day-old rats.

The authors studied the role of gamma-aminobutyric acid (GABA) in 2 types of forgetting of fear in the developing rat. One type of forgetting studied was that observed after an intermediate retention interval (the "Kamin effect"); the other type studied was that observed after a longer interval (infantile amnesia). Rats were given pairings of an auditory conditioned stimulus with shock, and learned fear was assessed by freezing. Forgetting at an intermediate retention interval (1 hr) was not alleviated by the GABAA receptor partial inverse agonist FG7142 (0, 1, 5, or 10 mg/kg), whereas forgetting at a longer retention interval (48 hr) was alleviated. These results suggest that in the developing rat, forgetting observed at different retention intervals is mediated by different physiological mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogenetic differences in the expression of conditioned stimulus conditioning: effects of retention interval

Preweanling 17-day-old rats were tested for retention of the conditioned emotional response after a 5-min or 24-hr retention interval. For a variety of conditioning parameters (i.e., variation in conditioned stimulus modality, unconditioned stimulus intensity, number of training trials), conditioned responding was consistently weaker after 5 min than after 24 hr. This apparent "incubation," or "hypermnesic," effect was not found in adult rats, even when comparable conditioning levels were indicated on the 24-hr test. The transient short-term retention deficit observed in 17-day-old preweanlings was alleviated by placing the pup in its home cage during the 5-min retention interval or by extending the conditioning session. Fifteen-day-old rat pups did not benefit from home cage exposure or extended training and displayed the transient short-term retention deficit regardless. The results are discussed in terms of age-related effects on time-dependent memory consolidation.     

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)     

Role of primary motivation in stimulus preexposure effects.

It is currently a matter of debate whether the deficit in conditioning observed after stimulus preexposure is one of acquisition or one of performance. The major criticism of performance-based theories is their inability to specify what is learned during nonreinforced preexposure that may influence subsequent acquisition of conditioned responding. Experiments 1 and 2 used an excitatory appetitive conditioning procedure and Experiment 3 used an inhibitory appetitive conditioning procedure, with rats as subjects, and consistently found that the effects of preexposure to a stimulus transferred to conditioning only when the reinforcer was relevant to the motivational state in which that preexposure was conducted. This finding suggests that during preexposure, rats learn that a stimulus is unrelated to events of relevance to their current motivational state. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Amygdala Modulates Hippocampus-Dependent Context Memory Formation and Stores Cue-Shock Associations.

Preexposing rats to the context facilitates subsequent contextual fear conditioning. This effect depends on the hippocampus (J. W. Rudy, R. M. Barrientos, & R. C. O'Reilly, 2002). The authors report that inactivating the basolateral region of the amygdala (BLA) by injecting muscimol, a GABAA agonist, before or after preexposure reduced this effect. In contrast, bilateral injections of anisomycin, a protein synthesis inhibitor, into BLA did not impair the consolidation of the context memory. However, when injected after fear conditioning, anisomycin impaired consolidation of both contextual and auditory-cue fear conditioning. Results are consistent with 2 ideas about the amygdala's contribution to memory: (a) It modulates memory formation in other regions of the brain, and (b) it is a storage site for cue-shock associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual control over conditioned responding in a latent inhibition paradigm.

We used 1-, 2-, and 3-context designs to study the control exerted by contexts over freezing in rats exposed to a conditioned stimulus (CS) in advance of its pairing with a shock unconditioned stimulus. The latent inhibition observed when preexposure, conditioning, and testing occurred in the same context was attenuated if preexposure occurred in a different context to conditioning and testing. Latent inhibition (i.e., attenuated performance) was restored in a CS-specific manner if preexposure and testing occurred in the same context and conditioning in a different one. Latent inhibition was also reduced by a long retention interval but remained specific for a particular context–CS relation. Finally, CS preexposure resulted in contextual control over the expression of excitatory conditioned performance. The results are discussed in terms of memory, associative, and associative-performance models of CS-preexposure effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Single neurons in the medial prefrontal cortex of the rat exhibit tonic and phasic coding during trace fear conditioning.

Trace fear conditioning is a learning task that requires the association of an auditory conditioned stimulus (CS) and a shock unconditioned stimulus (US) that are separated by a 20-s trace interval. Single neuron activity was recorded from the prelimbic and infralimbic areas of the medial prefrontal cortex in rats during trace fear conditioning or nonassociative unpaired training. Prelimbic neurons showed learning-related increases in activity to the CS and US, whereas infralimbic neurons showed learning-related decreases in activity to these stimuli. A subset of prelimbic neurons exhibited sustained increases in activity during the trace interval. These sustained prelimbic responses may provide a bridging code that allows for overlapping representations of CS and US information within the trace fear conditioning circuit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporally graded, context-specific retrograde amnesia and its alleviation by context preexposure: Effects of postconditioning exposures to morphine in the rat.

Five experiments studied retrograde impairments in Pavlovian fear conditioning following prolonged exposure to the opioid receptor agonist morphine. Injections of morphine commencing 1-7 days but not 14 days after conditioning produced amnesia for that conditioning episode. This amnesia was (a) selective such that morphine impaired freezing to the conditioning context but not to the auditory conditioned stimulus, (b) independent of the interval between the last injection of morphine and test, and (c) accompanied by a failure of contextual discrimination. Context preexposure protected context conditioning and discrimination from the amnestic effects of morphine. These results show that retrograde deficits in contextual fear conditioning are mediated by failures to consolidate a contextual representation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Outcome Pre- and Postexposure Effects: Retention Interval Interacts With Primacy and Recency.

Effects of outcome-alone pretraining and posttraining exposure were investigated in conditioned suppression experiments conducted within a sensory preconditioning preparation with rats. Experiment 1 found that interference by outcome postexposure was stronger than that by outcome preexposure, suggesting a recency effect. Experiment 2 found that after a long retention interval, outcome preexposure produced more interference than outcome postexposure, suggesting a shift from recency to primacy with increasing retention interval. Experiment 3 showed that presentation of a priming stimulus that had been embedded within the earlier phase of treatment also caused a shift from recency to primacy. These results suggest that, at least in a sensory preconditioning paradigm, retrievability of outcome-alone exposure memory is an important determinant of any outcome-alone exposure effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Factors governing single-trial contextual fear conditioning in the weanling rat.

Although contextual fear conditioning emerges later in development than explicit-cue fear conditioning, little is known about the stimulus parameters and biological substrates required at early ages. The authors adapted methods for investigating hippocampus function in adult rodents to identify determinants of contextual fear conditioning in developing rats. Experiment 1 examined the duration of exposure required by weanling rats at postnatal day (PND) 23 to demonstrate contextual fear conditioning. This experiment demonstrated that 30 s of context exposure is sufficient to support conditioning. Furthermore, preexposure enhanced conditioning to an immediate footshock, the context preexposure facilitation effect (CPFE), but had no effect on contextual conditioning to a delayed shock. Experiment 2 demonstrated that N-methyl-D-aspartate (NMDA) receptor inactivation during preexposure impairs contextual learning at PND 23. Thus, the conjuctive representations underlying the CPFE are NMDA-dependent as early as PND23 in the rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NMDA Receptor Modulation of Incidental Learning in Pavlovian Context Conditioning.

Rats exposed to a footshock show conditional fear when reexposed to the shock context. Immediate presentation of shock after placement in the context significantly reduces this fear. Preexposure to the context in the absence of shock, coupled with a minimum preshock interval during training, overcomes this immediate shock deficit. Because rats learn about the context during preexposure and express that learning after being reinforced, the context preexposure effect is an aversive analogue of latent learning. The authors examined the effect of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphovalerate (APV) on the facilitatory effect of context preexposure. Rats were preexposed to a chamber after APV administration. The next day they were placed in the same chamber without drug and received shock 35 s later. APV blocked the facilitatory effect of preexposure. Therefore NMDA receptors are important for contextual latent learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Isolation reduces contextual but not auditory-cue fear conditioning: A role for endogenous opioids.

Isolation for several hours after fear conditioning reduces contextual but not auditory-cue fear conditioning (J. W. Rudy, 1996). This isolation effect is reversed by both centrally and peripherally acting opioid receptor antagonists. As in isolation, systemically administered morphine given immediately after conditioning also reduces contextual fear conditioning. Morphine's effect is also reversed by both centrally and peripherally acting opioid receptor antagonists. Exposure to the conditioning context has been shown to eliminate the effect of isolation on contextual fear conditioning (J. W. Rudy, 1996). Context preexposure also eliminated the effect of morphine on contextual fear conditioning. These results imply that opioids released in the periphery play an important role in producing the isolation effect and that they do so by disrupting the postconditioning memory consolidation processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences, context preexposure, and the immediate shock deficit in Pavlovian context conditioning with mice.

The acquisition of context fear in rats is affected by variables such as the sex of the animal, the placement to shock interval (PSI), and preexposure to the context. The current experiments assessed the effects of these variables on context conditioning in mice (C57BL/6). In Experiment 1, mice were placed in a chamber and received a single shock 5 s, 20 s, 40 s, 60 s, 180 s, or 720 s later. Increasing the PSI produced corresponding increases in conditional freezing during the context test. In addition, male mice acquired more context conditioning than female mice did but only at intermediate PSIs. In Experiment 2, preexposure to the context before training alleviated the sex difference found with an intermediate PSI. The results are discussed in terms of configural learning theory and are argued to be contrary to the predictions of scalar expectancy theory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blocking of a CS–US association by a US–US association.

Pigeons were autoshaped with a keylight as the conditioned stimulus (CS) and food as the unconditioned stimulus (US). Preexposure to repeated US presentations was followed by training sessions in which a single US preceded a single CS–US pairing. Preexposure blocked conditioning to the CS only when the interval between the prior US and the US in the US–CS pairing (critical interval) was equal to the US–US interval in preexposure. Blocking was examined as a function of the length of the critical interval and the amount of preexposure. The hypothesis that blocking occurs because prior US predicts the time of arrival of the US in the CS–US pairing was supported by a reduction in blocking when USs separated by intervals longer than the critical interval were added to preexposure sessions. Certain other interpretations of these results were tested and rejected. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Isolation disrupts retention in preweanling rat pups.

Expression of an olfactory memory in 18-day-old rat pups was examined in eight experiments following brief manipulations of environmental conditions prior to a retention test. In the first experiment we found that retention was disrupted if a pup was placed in isolation for 3 hr prior to the retention test. The retention deficit persisted even when pups had 3-hr exposure to an anesthetized dam and siblings before testing. However, there was no deficit in retention if pups spent the pretest interval with a nonlactating foster dam, their father, or littermates. Finally, we found that this deficit in retention could be alleviated by cuing treatments that preceded the retention test following isolation. Both discrete cues used during training and returning the pup to the home cage with parents and siblings for 3 hr were found to alleviate the retention deficit caused by isolation. These data demonstrate that housing conditions can influence postacquisition memory processes in the young animal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Involvement of NMDA receptors within the amygdala in short- versus long-term memory for fear conditioning as assessed with fear-potentiated startle.

Pretraining intra-amygdala infusions of the NMDA receptor antagonist, D,L-AP5, block fear-potentiated startle in rats tested 24+ hr after training. This may reflect a failure of either acquisition or retention. To evaluate these alternatives, rats were tested for fear-potentiated startle during fear conditioning (30 light-shock pairings [0.6 mA shock]), as well as 1–30 min and 48 hr after fear conditioning. Amygdala lesions abolishes fear-potentiated startle at all train-test intervals. Intra-amygdala AP5 infusions (25 nmol/side) abolished fear-potentiated startle during the long-term test and had partial effects at shorter train-test intervals. When the level of fear-potentiated startle during the short-term test was lowered to that of the 48-hr test (i.e., by training rats with a lower, 0.3 mA footshock), AP5 abolished fear-potentiated startle at each timepoint. Thus, amygdala NMDA receptors appear to participate in the initial acquisition of fear memories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)