A Comparison of Latent Inhibition and Learned Irrelevance Pre-Exposure Effects in Rabbit and Human Eyeblink Conditioning

The learning of an association between a CS and a US can be retarded by unreinforced presentations of the CS alone (termed latent inhibition or LI) or by un-correlated presentations of the CS and US (termed learned irrelevance or LIRR). In rabbit eyeblink conditioning, there have been some recent failures to replicate LI. LIRR has been hypothesized as producing a stronger retardation effect than LI based on both empirical studies and computational models. In the work presented here, we examined the relative strength of LI and LIRR in eyeblink conditioning in rabbits and humans. In both species, a number of preexposure trials sufficient to produce LIRR failed to produce LI (Experiments 1 & 3). Doubling the number of CS pre-exposures did produce LI in rabbits (Experiment 2), but not in humans (Experiment 4). LI was demonstrated in humans only after manipulations including an increased inter-trial interval or ITI (Experiment 5). Overall, it appears that LIRR is a more easily producible pre-exposure retardation effect than LI for eyeblink conditioning in both rabbits and humans. Several theoretical mechanisms for LI including the conditioned attention theory, stimulus compression, novelty, and the switching theory are discussed as possible explanations for the differences between LIRR and LI. Overall, future work involving testing the neural substrates of pre-exposure effects may benefit from the use of LIRR rather than LI.     

Latent inhibition and stimulus generalization of the classically conditioned nictitating membrane response in rabbits (Oryctolagus cuniculus) following dorsal hippocampal ablation.

Rabbits received 0 to 450 exposures of a tone conditioned stimulus (CS) prior to classical defensive conditioning of the nicitating membrane response based on an infraorbital eye shock unconditioned stimulus. Tone preexposure resulted in retarded conditioning in normal rabbits. This latent inhibition effect was not present in animals with bilateral dorsal hippocampectomy produced by aspiration. Control animals with bilateral neocortical and callosal aspiration lesions demonstrated a latent inhibition effect similar to that shown by normal nonoperated animals. The failure of CS preexposure to retard conditioning in hippocampal rabbits was not due to differences in threshold of the conditioned response to the CS or to differences in response mechanisms as determined by tests of habituation and dishabituation of the unconditioned response. A subsequent experiment employed combined-cue summation tests to confirm the fact that preexposure did not endow the tone with conditioned as well as latent inhibitiory properties. Finally, tests of stimulus generalization along the auditory frequency dimension indicated flatter relative gradients for hippocampals than for nonoperated controls, with cortical controls in between. These findings were discussed in terms of Douglas' model of hippocampal function.     

Selective hippocampal lesions disrupt a novel cue effect but fail to eliminate blocking in rabbit eyeblink conditioning

The classical conditioning task of blocking involves the adding of a novel but redundant stimulus to a previously trained stimulus. Both blocking and novelty detection are thought to involve the hippocampus. Previously, Solomon (1977) found that nonselective aspiration lesions of the hippocampal region eliminated blocking in rabbit eyeblink conditioning. We tested the effects of selective ibotenic acid lesions of the hippocampus on blocking, as well as on novelty detection, when training is switched from a tone conditioned stimulus (CS) to a compound tone-light CS in eyeblink conditioning. Selective hippocampal lesions did not eliminate blocking but did lead to a facilitation of conditioned response (CR) acquisition to the tone and to the light, but not to the tone-light compound. Selective hippocampal lesions disrupted a CR decrement observed in sham surgical controls when transferred from tone training to tone-light training. It appears that although selective hippocampal lesions do not eliminate blocking in eyeblink conditioning, they do disrupt novelty detection and may facilitate learning to a previously blocked cue.     

Entorhinal but Not Hippocampal or Subicular Lesions Disrupt Latent Inhibition in Rats

Latent inhibition (LI) is the deficit of conditioning resulting from repeated nonreinforced preexposure to a conditioned stimulus before its pairing with an unconditioned stimulus. There are cumulative data showing that large lesions of the hippocampal formation disrupt LI. However, the effects of selective lesions of the different components of the hippocampal formation have never been directly addressed in the same study and conditioning paradigm. The first experiment of the present study aimed at investigating the effects of excitotoxic lesions of the hippocampus, subiculum, or entorhinal cortex on LI in an "off-baseline"-conditioned emotional response procedure. Hippocampus or subiculum lesions had no effect on either LI or conditioning. In contrast, entorhinal cortex lesions disrupted LI without modifying conditioning. In Experiment 2, locomotor activity in a novel environment was assessed in the same rats. Whereas lesions of hippocampus increased locomotor activity, lesions of the subiculum or the entorhinal cortex were devoid of effect. Although both LI and habituation to novel environmental cues are thought to involve interactions between the hippocampal formation and the mesolimbic pathway, these results indicate a functional dissociation between the hippocampus and the entorhinal cortex.     

A comparison of latent inhibition and learned irrelevance pre-exposure effects in rabbit and human eyeblink conditioning

The learning of an association between a CS and a US can be retarded by unreinforced presentations of the CS alone (termed latent inhibition or LI) or by un-correlated presentations of the CS and US (termed learned irrelevance or LIRR). In rabbit eyeblink conditioning, there have been some recent failures to replicate LI. LIRR has been hypothesized as producing a stronger retardation effect than LI based on both empirical studies and computational models. In the work presented here, we examined the relative strength of LI and LIRR in eyeblink conditioning in rabbits and humans. In both species, a number of pre-exposure trials sufficient to produce LIRR failed to produce LI (Experiments 1 & 3). Doubling the number of CS pre-exposures did produce LI in rabbits (Experiment 2), but not in humans (Experiment 4). LI was demonstrated in humans only after manipulations including an increased inter-trial interval or ITI (Experiment 5). Overall, it appears that LIRR is a more easily producible pre-exposure retardation effect than LI for eyeblink conditioning in both rabbits and humans. Several theoretical mechanisms for LI including the conditioned attention theory, stimulus compression, novelty, and the switching theory are discussed as possible explanations for the differences between LIRR and LI. Overall, future work involving testing the neural substrates of pre-exposure effects may benefit from the use of LIRR rather than LI.     

Contextual Control of Latent Inhibition by the Reinforcer

Three experiments examined the contextual control of latent inhibition (LI) by the unconditioned stimulus (US) using a within-subjects conditioned suppression procedure with rats. The effect of reducing the context change produced by the introduction of the shock US was investigated by presenting this US during preexposure to the conditioned stimulus (CS). Although limited CS preexposure in the absence of the US had no impact on subsequent conditioning, preexposure in the presence of the shock retarded both excitatory and inhibitory conditioning. We conclude that the introduction of the US during the conditioning phase of a normal LI experiment can produce a contextual change that reduces the observed magnitude of LI.     

Effects of Early Hippocampal Lesions on Trace, Delay, and Long-Delay Eyeblink Conditioning in Developing Rats

The effects of bilateral hippocampal aspiration lesions on later acquisition of eyeblink conditioning were examined in developing Long-Evans rat pups. Lesions on postnatal day (PND) 10 were followed by evaluation of trace eyeblink conditioning (Experiment 1) and delay eyeblink conditioning (Experiment 2) on PND 25. Pairings of a tone conditioned stimulus (CS) and periocular shock unconditioned stimulus (US, 100 ms) were presented in one of three conditioning paradigms: trace (380 ms CS, 500 ms trace interval, 880 ms interstimulus interval [ISI]), standard delay (380 ms CS, 280 ms ISI), or long delay (980 ms CS, 880 ms ISI). The results of two experiments indicated that hippocampal lesions impaired trace eyeblink conditioning more than either type of delay conditioning. In light of our previous work on the ontogeny of trace, delay, and long-delay eyeblink conditioning (Ivkovich, Paczkowski, & Stanton, 2000) showing that trace and long-delay eyeblink conditioning had similar ontogenetic profiles, the current data suggest that during ontogeny hippocampal maturation may be more important for the short-term memory component than for the long-ISI component of trace eyeblink conditioning. The late development of conditioning over long ISIs may depend on a separate process such as protracted development of cerebellar cortex.     

Role of the hippocampus in blocking and conditioned inhibition of the rabbit's nictitating membrane response.

Bilateral aspiration of the dorsal hippocampus produced a disrupttion of blocking of the rabbit's nictitating membrane response in Kamin's two-stage paradigm (Experiment 1) but had no effect on the formation of a Pavlovian conditioned inhibitor (Experiment 2). The results of Experiment 1 indicated that normal animals and those with cortical lesions given conditioning to a light-plus-tone conditioned stimulus (CS) gave conditioned responses (CRs) to both the light and the tone during nonreinforced presentations of each (test phase). If, however, compound conditioning was preceded by tone acquisition, only the tone elicited a CR during testing; that is, blocking was observed. In rabbits with hippocampal lesions, however, CRs were given to both the light and the tone during testing whether or not compound conditioning was preceded by tone acquisition. The data from Experiment 2 showed that rabbits with hippocampal lesions could discriminate as well as normal rabbits and those with cortical lesions between a light (CS+) and light plus tone (CS-). In addition, when the inhibitory tone was subsequently paired with the unconditioned stimulus in retardation testing, animals in all three lesion conditions acquired the CR at the same rate. Thus, it appears that hippocampal lesions do not disrupt conditioned inhibition. The results of these experiments were taken as support for the view that the hippocampus is responsible for "tuning out" stimuli that have no adaptive value to the organism.     

Analysis of the learned irrelevance effect in appetitive Pavlovian conditioning

In Experiments 1 and 2 rats received uncorrelated presentations of a light conditioned stimulus (CS) and a food unconditioned stimulus (US) on each day of a preexposure phase. Control subjects received the same number of USs during the first half of preexposure and the same number of CSs during the second. Uncorrelated preexposure retarded inhibitory conditioning. Experiment 3 showed, however, that the different patterns of US preexposure experienced by the two groups could in itself influence the course of subsequent inhibitory conditioning. When this factor was equated by restricting the uncorrelated treatment to the first half of the pre-exposure phase (Experiment 2) or by extending the control treatment throughout the phase (Experiment 4) it was found that uncorrelated preexposure retarded excitatory conditioning, but facilitated inhibitory conditioning. This outcome challenges an interpretation in terms of the concept of learned irrelevance, which predicts that uncorrelated preexposure should retard both forms of conditioning.     

Pavlovian heart rate and jaw movement conditioning in the rabbit: effects of medial prefrontal lesions

An experiment was conducted in which jaw movements (JM) and heart rate (HR) were concomitantly assessed in rabbits during simple Pavlovian conditioning. A 2-s 1200-Hz tone was the conditioned stimulus (CS) and an intraoral 1-cc pulse of 0.5 M sucrose-water solution was the unconditioned stimulus (US). Sham and medial prefrontal (mPFC)-lesioned animals received paired CS/US training with a 70- to 75-dB CS and were compared with sham- and mPFC-lesioned animals that received explicitly unpaired CS/US presentations. The percentages of JM CRs were significantly greater in the paired than the unpaired groups, but mPFC lesions had no effect on this measure. Conditioned HR decelerations occurred only in the paired groups and then only during the first session of training. Moreover, these CS-evoked cardiac decelerations were somewhat attenuated by the mPFC lesion. CS-evoked HR accelerations, which were significantly greater in unpaired than in paired animals, occurred during the four subsequent sessions. These results suggest that a CS-evoked cardioinhibitory process, mediated by the mPFC, is engendered by Pavlovian appetitive conditioning, as has been previously demonstrated for aversive conditioning. However, during JM conditioning these inhibitory changes are quickly replaced by tachycardia, possibly related to increased nonspecific somatomotor activity, since the tachycardia was somewhat greater in the unpaired animals.     

The Influence of Retention Interval on the US Preexposure Effect: Changes in Contextual Blocking over Time

A number of studies manipulating the length of the interval between conditioning and testing indicate spontaneous recovery from overshadowing, suggesting that certain instances of overshadowing represent a deficit in memory retrieval rather than a failure of animals to form an association between the overshadowed stimulus and the US. The present series of experiments examined the influence of lengthening the retention interval on blocking, another stimulus selection phenomenon that is typically interpreted as an acquisition deficit. The results indicated that when subjects were tested shortly (3 days) after training conditioning to a taste blocked subsequent conditioning to an odor conditioned in compound with that taste (Experiment 1), whereas prior conditioning to an odor did not block subsequent conditioning to a taste conditioned in compound with that odor (Experiment 2). This pattern of results was essentially unchanged when testing occurred at a longer (21-day) retention interval. However, there was evidence of a US preexposure effect in Experiment 2 when subjects in the US ONLY control condition were tested at the 3-day retention interval, but not when testing occurred 21 days after conditioning. Experiments 3 and 4 examined whether this loss of the US preexposure effect over time might actually represent a change in the degree of contextual blocking as the retention interval is lengthened. Exposure to the conditioning context either during the interval between Phase 1 and Phase 2 of conditioning (Experiment 3) or prior to Phase 1 of conditioning (Experiment 4) alleviated this US preexposure effect suggesting that the loss of the US preexposure effect as the retention interval is lengthened observed in Experiment 2 is due to changes in the degree of blocking by contextual stimuli over time. The results are discussed in terms of differential susceptibility of forgetting of two functional roles played by a contextual stimuli in the current situation-context as a CS and context as a retrieval cue for other CS-US associations.     

Posttraining prefrontal lesions impair jaw movement conditioning performance,but have no effect on accompanying heart rate changes

This experiment examined the role of the medial prefrontal cortex (mPFC) in regulating learned autonomic and somatomotor responses in rabbits using appetitive Pavlovian conditioning. Interstimulus interval (ISI) duration [i.e., the time between the onset of the conditioned stimulus (CS) and unconditioned stimulus (US)] was manipulated in order to determine whether ISI duration was related to the heart rate (HR) responses obtained during conditioning. Two groups received either a 1- or a 4-s ISI, with a tone as the CS and an intraoral pulse of water as the US. Another two groups received explicitly unpaired presentations of either the 1- or 4-s tone CS and water US. Few conditioned jaw movement (JM) or HR conditioned responses (CRs) were observed in the unpaired conditions. Significant JM conditioning was, however, elicited by the paired conditions, especially to the 4-s ISI. Consistent CS-evoked HR accelerations were observed in both ISI conditions. After five sessions of training, the mPFC was lesioned in half the animals. A separate group of paired animals received sham lesions. After surgical recovery, all animals received 3 days of postoperative training. During the first postoperative training session, JM CRs significantly declined in both groups with mPFC lesions in comparison to the groups with sham lesions. The mPFC lesions, however, did not affect the CS-evoked cardiac accelerations, which again occurred during postoperative training.     

Effects of hippocampal stimulation on acquisition, extinction and generalization of conditioned suppression in the rat.

Rats implanted with electrodes in the dorsal or ventral hippocampus received posttrial stimulation in training sessions with footshock reinforcement. Afterdischarges without overt seizures were consistently without effect on the rate of acquisition of suppression of licking during an auditory conditioned stimulus (CS), although conditioning was retarded by the delivery of distracting stimuli following footshock. The rate of conditioning remained insensitive to elicitation of dorsal hippocampal afterdischarges (DHAD) despite subsequent alterations of session length, intertrial interval and preexposure to the CS. However, faster extinction of suppression occurred following DHAD, suggesting a limited but essential role of the hippocampus in addressing stored information.     

When congruence breeds preference: the influence of selective attention processes on evaluative conditioning

We investigated in two experiments whether selective attention processes modulate evaluative conditioning (EC). Based on the fact that the typical stimuli in an EC paradigm involve an affect-laden unconditioned stimulus (US) and a neutral conditioned stimulus (CS), we started from the assumption that learning might depend in part upon selective attention to the US. Attention to the US was manipulated by including a variant of the Eriksen flanker task in the EC paradigm. Similarly to the original Flanker paradigm, we implemented a target-distracter logic by introducing the CS as the task-relevant stimulus (i.e. the target) to which the participants had to respond and the US as a task-irrelevant distracter. Experiment 1 showed that CS–US congruence modulated EC if the CS had to be selected against the US. Specifically, EC was more pronounced for congruent CS–US pairs as compared to incongruent CS–US pairs. Experiment 2 disentangled CS–US congruence and CS–US compatibility and suggested that it is indeed CS–US stimulus congruence rather than CS–US response compatibility that modulates EC.     

Essential neuronal pathways for reflex and conditioned response initiation in an intracerebellar stimulation paradigm and the impact of unconditioned stimulus preexposure on learning rate

It has been demonstrated previously that pairing of tone CS and intracerebellar stimulation of lobule HVI white matter as the US produces conditioning that is robust and in many ways similar to that obtained with an airpuff US. The first study in this report addressed the effect of interpositus lesions on conditioned performance in rabbits trained with white matter stimulation as the US. It was found that interpositus lesions effectively eliminated the CR irrespective of the behavioral response measured. In addition, it was shown that the interpositus lesions also abolished the UR, providing strong evidence that the effects of the electrical stimulation were confined to the cerebellum and did not require the activation of brainstem structures. The second experiment examined performance on US-alone trials of varying durations. Response initiation within 100 ms of the US onset, regardless of US duration, indicated that reflex generation could not be due to rebound excitation of the interpositus following termination of Purkinje cell inhibition of that structure but instead likely reflects orthodromic activation of interpositus neurons via climbing fiber and/or mossy fiber collaterals. The impact of US preexposure on associative conditioning in this paradigm was also determined. Animals which received only 108 US-alone trials were massively impaired during subsequent training compared to rabbits that received fewer than 12 US-alone trials.     

Learned irrelevance: A contemporary overview

This article reviews the recent literature on the topic of learned irrelevance. It asks whether the retardation of subsequent conditioning produced by uncorrelated preexposure is indeed the result of the animal learning that a conditioned stimulus (CS) and unconditioned stimulus (US) are unrelated, or whether it is better explained either as a result of the context specificity of latent inhibition, or as some other artefact of the uncorrelated schedule employed. The conclusion is that there is as yet no good evidence to support the existence of a “genuine” learned irrelevance effect.     

Preexposure to the CS alone,US alone,or CS and US uncorrelated: Latent inhibition,blocking by context or learned irrelevance?

Three experiments on conditioned suppression in rats examined the extent to which preexposure to the CS, the US, or uncorrelated presentations of both interfere with future conditioning. Experiment 1 suggested that the interference caused by preexposure to the US alone may result from blocking by contextual cues: signaling the US during preexposure attenuated the interference. Experiment 2 demonstrated that signaling the US by another stimulus did not attenuate the interference caused by exposure to uncorrelated presentations of CS and US. Experiment 3 replicated the results of Experiments 1 and 2 and directly compared the magnitude of these deficits. The results of these experiments imply that the effects of exposure to uncorrelated presentations of CS and US are not reducible to the sum of the effects of exposure to CS or US alone.     

The influence of flavor preexposure and test interval on conditioned taste aversions in the rat

The effects of flavor preexposure and test interval on conditioned taste aversions were examined in four experiments. In the first three experiments, prior experience with a flavor different from that used as a conditioned-stimulus (CS) produced attenuated aversions when testing occurred after a 1-day interval but not after a 21-day interval. Preexposure to the same stimulus used as a CS produced attenuated aversions at both 1- and 21-day intervals. In Experiment 4, a delay interval between flavor preexposure and conditioning eliminated the attenuating effect of preexposure, but only when different stimuli were used for preexposure and conditioning. These data could not be easily accounted for by contemporary interpretations of preexposure as an event that interferes with subsequent acquisition of a conditioned aversion. An alternative retrieval interference hypothesis was outlined.     

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

In two experiments we examined factors that contribute to retarded emergence of conditioned responding to a conditioned stimulus (CS) trained in a context in which unsignaled unconditioned stimuli (USs) had previously been administered. In both experiments water-deprived rats were used in a conditioned lick suppression task to measure the conditioned response elicitation potential of the CS and the training context. From Experiment 1 we determined that nonreinforced exposure to the excitatory context after US preexposure and prior to CS-US pairings in that context eliminated the conditioned response deficit observed on a subsequent test of the CS. The recovery from the US preexposure deficit was nearly as great in animals that received nonreinforced exposure to the excitatory training context after the CS-US pairings but prior to the ultimate test of the CS. From Experiment 2 we 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. In total, these experiments suggest that context-US associations partially mask the expression of a learned CS-US association. These results are discussed in terms of recent models of conditioned response generation.     

Overshadowing of subsequent events and recovery thereafter

Four experiments using a conditioned lick suppression preparation with rats were conducted to examine whether overshadowing of subsequent events could be obtained in Pavlovian backward conditioning (i.e. unconditioned stimulus [US] before conditioned stimulus [CS]), and to determine whether such overshadowing could be reversed without further training with the overshadowed CS, as has been reported in overshadowing of antecedent events. In Experiment 1, a backward-conditioned CS overshadowed a second backward-conditioned CS. Two posttraining manipulations, extinction of the overshadowing CS (Experiment 2) and shifting of the temporal relationship of the overshadowing CS to the US (Experiment 3), increased responding to the overshadowed CS. These results constitute the first unambiguous demonstration of stimulus competition between subsequent events using first-order conditioning, and they show that, like overshadowing with forward conditioning, such overshadowing is due, at least in part if not completely, to a failure to express information that had been acquired.