Latent inhibition in the developing rat: an examination of context-specific effects

Latent inhibition (LI) refers to the reduction in conditioned responding when the conditioned stimulus (CS) is preexposed prior to CS-unconditioned stimulus pairings. Experiment 1a demonstrated that preexposure to an odor CS prior to odor-shock pairings markedly reduced conditioned freezing in 25-day-old rats; however, this LI effect was observed only if odor preexposure and odor-shock pairings occurred in the same context (i.e., LI was context-specific at this age). The results of Experiment 1b showed that 18-day-olds also exhibited LI, but this effect was not context-specific at this age. In Experiment 2, rats were preexposed to the odor at 18 days of age and given odor-shock pairings at 25 days of age. These rats exhibited context-specific latent inhibition, suggesting that 18-day-old rats encoded the preexposure context. In Experiment 3, all parameters were identical to Experiment 2, with the exception that odor-shock pairings were given at approximately PN18 and testing occurred at approximately PN25. These rats exhibited latent inhibition at test, but this effect was not context-specific. The results of this study suggest that (a) PN18 rats can exhibit latent inhibition, and (b) the expression of context-specific latent inhibition depends on the age at which conditioning occurs.     

Conditioning of aversion to an odor paired with peripheral shock in the developing rat

Four experiments examined an apparent inability to associate, or severe deficiency in associating, an odor and a footshock during the first 2 weeks of life in the rat, a cue-to-consequence relationship that had formerly seemed age-dependent. With a particular classical conditioning procedure, however, significiant conditioning occurred on postnatal Days 6 and 10 with relatively few conditioning trials; the procedure employed an odor explicitly unpaired with footshock (CS?), as well as an odor paired with footshock (CS+) (Experiment I). Experiment II assessed the contribution of a CS? exposure in the conditioning of rats 8, 15, or 50 days of age. For 8-day-olds, exposure to both the CS+ and CS? resulted in conditioned aversion to the CS+ after eight but not one conditioning trials, but neither 1 nor eight trials with only a CS+ produced conditioning. For 15- and 50-day-olds, conditioning to the CS+ odor was significant after one trial with, but not without, a specific CS? with eight trials, however, conditioning was significant with or without the specific CS?. It was verified with the 50-day-olds in Experiment III that aversion to the CS+ was conditioned with a single trial only if a CS? had been presented, with a slight trend toward superior conditioning if the CS? preceded rather than followed the CS+ during conditioning. Experiment IV tested the hypothesis that exposure to the distinctive CS? odor sensitzes the animal to the specific properties of the CS+ odor. Fifteen and 50-day-old rats were given one conditioning trial with a CS+ odor that was either unaccompanied by a CS? or that was presented with a CS? odor in the same context as the CS+ or in a different context. For both 15? and 50-day-old rats, conditioning to the CS+ occurred only for animals given the CS? in the same context as the CS+, indicating that the hypothesis should be rejected. The results generally indicate rapid and substantial odor-footshock conditioning in rats as young as 6 days of age, with CS-exposure established as perhaps especially significant for conditioning early in life, but important for rats of all ages tested, from infancy to adulthood.     

A developmental analysis of contextual fear conditioning

Contextual fear conditioning by 18- and 23-day-old rats was compared in two training contexts, a transparent Plexiglas chamber or a black Plexiglas chamber. As measured by a conditioned defensive freezing response, older rats displayed more contextual fear than younger rats. At both ages conditioning was (a) stronger in the black chamber than in the clear chamber, (b) a nonmonotonic function of retention interval, with freezing being greater at the immediate and 24-hr retention interval than at the 10-min interval, and (c) preexposure to the context 24 hr before conditioning enhanced conditioned freezing observed at the 10-min retention interval. Additional experiments suggest that rats at both ages acquire independent representations of the visual and tactile features of the context. These results support Rudy and Morledge's (1994) hypothesis that contextual fear conditioning is mediated by both a short-term and a long-term memory system and that long-term memory for contextual fear requires the consolidation of a representation of the context. They challenge their view that there is a qualitative developmental difference in long-term memory processes between 18- and 23-day-old rats. © 1996 John Wiley & Sons, Inc.     

Disruption of contextual freezing, but not contextual blocking of fear-potentiated startle, after lesions of the dorsal hippocampus

The role of the dorsal hippocampus in contextual fear conditioning was investigated with a contextual blocking paradigm. In Experiment 1, rats were given pairings of a light conditioned stimulus (CS) and footshock after preexposure either to footshock or to the context alone. The group preexposed to footshock showed poorer fear conditioning to the light CS, as measured by the fear-potentiated startle reflex. In Experiment 2, a group preexposed to footshock in the same context showed poorer fear conditioning to the light CS than did a group preexposed to footshock in a different context, indicating contextual blocking of fear-potentiated startle. In Experiment 3, lesions of the dorsal hippocampus had no effect on contextual blocking, even though contextual freezing was disrupted. The sparing of contextual blocking indicated that contextual memory was intact following hippocampal lesions, despite the disruption of contextual freezing.     

Ontogenetic differences in the effects of unpaired stimulus preexposure on eyeblink conditioning in the rat

Learned irrelevance (LIr) is a Pavlovian conditioning phenomenon in which random or unpaired preexposure to a conditional stimulus (CS) and to an unconditional stimulus (US) retards subsequent paired conditioning involving these stimuli. A previous developmental study of eyeblink conditioning in the rat suggested that LIr is not present on postnatal Day 20. Stanton, Fox, and Carter (1998) showed that unpaired preexposure to a CS and a US on postnatal Day 17 failed to retard (and, in fact, facilitated) subsequent paired conditioning involving these stimuli on postnatal Day 20. The present experiments were designed to further characterize the ontogeny of this phenomenon. In Experiment 1, LIr was observed when rat pups were tested for eyeblink conditioning as described in Stanton et al. (1998), except that preexposure occurred on postnatal Day 27, and acquisition testing occurred on postnatal Day 30. In Experiment 2, preexposure and acquisition both occurred on postnatal Day 30, and four types of preexposure were compared: chamber only, CS alone, US alone, or unpaired presentation of CS and US. Unpaired preexposure impaired acquisition relative to that of the remaining three groups, which did not differ. Experiment 3, showed that under the conditions of Experiment 2, LIr failed to appear on postnatal Day 20, but was observed on postnatal Days 25 and 30. These findings suggest that learning that events are unrelated emerges between postnatal Days 20 and 25 in the rat. Possible behavioral and neural mechanisms underlying this effect are discussed.     

Novel factors contributing to the expression of latent inhibition

Behavioral and neural correlates of latent inhibition (LI) during eyeblink conditioning were studied in 2 experiments. In Experiment 1, rabbits (Oryctolagus cuniculus) were conditioned after 8 days of tone conditioned stimulus (CS) presentations or 8 days of context-alone experience. LI was seen in the CS-preexposed rabbits when a relatively intense (5 psi) airpuff unconditioned stimulus was paired with the CS. In Experiment 2, rabbits were given 0, 4, or 8 days of CS preexposures or context-alone experience. Hippocampal activity was monitored from the 8-day CS- or context-exposure rabbits. The LI effect was seen only in rabbits given 4 days of CS preexposure, thus suggesting that LI depended largely on the rate of acquisition in the context-preexposed control group. The neural recordings showed that the hippocampus was sensitive to the relative novelty of the stimuli and the overall context, regardless of whether exposure to stimuli and context promoted LI.     

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 5s, 20 s, 40s, 60s, 180s, or 720s 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.     

Postconditioning recovery from the latent inhibition effect in conditioned taste aversion

Two experiments were conducted examining the effects of flavor (CS) preexposure on the retention of conditioned taste aversion. In Experiment 1, rats received preexposure to sucrose solution followed by a sucrose-illness pairing. The expected “latent inhibition” effect was obtained when testing occurred after a two-day but not an eleven-day training-to-test interval. Experiment 2 extended these results by employing five- and twenty-one-day training-to-test interval parameters and provided evidence that the stronger taste aversion displayed by preexposed subjects following long retention intervals is not attributable to differences in training consumption of sucrose solution. This posttraining increase in conditioned taste aversion (CTA) suggests that preexposure blocks expression of memory.     

Effects of Conditioned Stimulus Fear-Relevance and Preexposure on Expectancy and Electrodermal Measures of Human Pavlovian Conditioning

The present research investigated the effects of fear-relevance of the conditioned stimulus (CS) and CS preexposure on human electrodermal conditioning and on a continuous measure of expectancy of the unconditioned stimulus (US). Both experiments employed 20 preexposure, 8 acquisition, and 8 extinction trials in a differential Pavlovian conditioning paradigm with shock as the US. In Experiment 1 (N = 48), electrodermal conditioning was retarded by CS preexposure, but was not influenced by fear-relevance of the CS. Expectancy of the US was retarded by preexposure only in the fear-relevant condition. In Experiment 2 (N = 48), the CS/US contingencies was embedded in a visual masking task. Preexposure retarded both electrodermal conditioning and US expectancy. Neither measure was influenced by fear-relevance of the CS. However, fewer subjects in the preexposure condition learned the CS/US relationship and those who did, did so on later trial than those in the no-preexposure condition. Thus, the results indicated clear retardation of conditioning as a result of preexposure, but no reliable effect of fear-relevance.     

Cingulate cortical coding of context-dependent latent inhibition

Neuronal activity of the auditory thalamus, amygdala, cingulate cortex, and substantia nigra was recorded during the administration of a behavioral test for latent inhibition (LI) or the retardation of behavioral conditioning because of preexposure of the conditional stimulus (CS). Following CS preexposure, both the preexposed CS and a control CS predicted avoidable footshock. LI occurred as significantly fewer avoidance conditioned avoidance responses after the preexposed CS than after the control CS. Attenuation of neuronal responses to the preexposed CS, or neural LI, occurred in all monitored areas. One group of subjects (Oryctolagus cuniculus) then received context extinction, and additional groups experienced novel context exposure or handling. Context extinction enhanced behavioral responding to the preexposed CS, eliminating LI. Context extinction also eliminated cingulate cortical neural LI by enhancing posterior cingulate cortical responses to the preexposed CS and attenuating anterior cingulate cortical responses to the control CS. Present and past results are interpreted to indicate that LI is (a) a failure of response retrieval and/or expression mediated by interfering CS-context associations and (b) a product of interactions of the posterior cingulate cortex and the hippocampus.     

Effects of conditioned stimulus preexposure on human electrodermal conditioning

Two experiments investigated the effects of conditioned stimulus (CS) preexposure on Pavlovian differential conditioning and extinction of the skin conductance response. In both experiments, half the subjects were exposed to 20 presentations each of the CS+ and CS-, and the other half were exposed to control stimuli. CS duration was 8 sec. The unconditioned stimulus in Experiment 1 (N = 48) was a 1000 Hz tone of 80 dB which signalled a reaction time requirement, and in Experiment 2 (N = 48), it was a 1 sec burst of white noise at 105 dB. The results of Experiment 1 indicated that no-preexposure groups displayed more CS+/CS- differentiation than preexposure groups during acquisition and more resistance to extinction, at least for the first interval anticipatory response. In addition, the results of Experiment 2 indicated that no-preexposure groups displayed more differentiation than preexposure groups in terms of the second interval anticipatory response. These data constitute a demonstration of the latent inhibition effect with human subjects, and imply that there is an intrinsic relationship between the orienting response and the conditioning process.     

The influence of natural preference for tactile stimuli on appetitive learning in rat pups

Stimuli of the same modality tend to be organized along a “natural preference scale.” This study examined the ability of six- and nine-day-old rat pups to acquire appetitive learning, when the CS was one of two differently “naturally preferred” tactile stimuli (floor textures: rug and plywood). In Experiment 1, all pups showed a relative natural preference for the rug texture over the plywood texture. Pups conditioned on the plywood texture (exposed to a sibling pup as the US) showed a robust increase in preference for the conditioned texture whereas pups conditioned on the rug texture showed a different and more moderate pattern of acquisition. Developmental differences were found only in extinction of the conditioned response: six-day-old (but not nine-day-old) pups displayed extinction of the response over four trials. Experiment 2 indicated that preexposure to the rug CS prior to conditioning (latent inhibition) did not interfere with the learning process on the rug texture. Two major alternative explanations for the differential learning patterns are discussed: motivational and catecholaminergic influences on learning. The results suggest that natural preferences may modulate early learning and memory processes. © 1997 John Wiley & Sons, Inc. Dev Psychobiol 30: 29–30, 1997     

Disruption of latent inhibition following systemic administration of parachlorophenylalanine (PCPA).

Rats received either 0 or 30 preexposures to a tone which was later used as a CS in a two-way active avoidance task. Tone preexposure resulted in retarded conditioning in normal animals. This latent inhibition effect, however, was not present in rats treated with parachlorophenylalanine. A second experiment used the combined-cue summation test to verify the fact that stimulus preexposure endowed the tone with latent and not conditioned inhibitory properties. The results were discussed in terms of the role of the serotonergic mesolimbic system in tuning out irrelevant stimuli.     

The unconditioned stimulus pre‐exposure effect in preweanling rats in taste aversion learning: Role of the training context and injection cues

The unconditioned stimulus pre‐exposure effect (US‐PE) refers to the interference paradigm in which acquisition of the conditioned response is retarded due to prior experience with the US. Most studies analyzing the psychological mechanisms underlying this effect have been conducted with adult rats. The most widely accepted hypothesis explains this effect as a contextual blocking effect. Contextual cues associated with the US block the conditioned stimulus (CS)‐US association during conditioning. The modulatory role of a context devoid of distinctive olfactory attributes is not observable until approximately PD23 in rats, including modulation of interference paradigms such as latent inhibition or extinction. In this study, we analyzed US‐PE in preweanling rats along with the role of the training context in this effect in terms of conditioned taste aversion preparation. Pre‐exposure to LiCl before conditioning retarded the acquisition of taste aversion. The US‐PE was observed in preweanling rats when, during pre‐exposure, subjects were exposed to the conditioning context, and this effect was not attenuated either by the administration of the US in a familiar environment (Experiment 1a), or by the presence of an alternative, more salient context during pre‐exposure (Experiment 1b). Additionally, the US‐PE was still observed when the route by which the US was administered was changed between the pre‐exposure and conditioning phases (Experiment 2a) as well as when the injection cues were removed during conditioning (Experiment 2b). These experiments show a strong US‐PE in preweanling rats and fail to support the contextual blocking hypothesis, at least in this stage of ontogeny. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 193–204, 2013     

Ontogeny of two-way avoidance in male and female rats

In Experiment I, 17-, 21-, 36-, 51-, 90-, and 200-day-old male and female rats were given a single session of 100 two-way avoidance (TWA) trials. In the 2nd experiment, males and females of these ages and 15 and 28 days of age that were obtained from a different source, weaned at a later age, and housed differently received TWA training. Results of both studies showed that avoidance of 15-, 17-, and 21-day-old rats is low, but avoidance increases from 21 to 51 days of age. Avoidance of 95- and 200-day-old animals was generally lower than 51-day-old rats. No significant gender differences appeared until 90 days of age; at this age avoidance of males was lower than females. In Experiment III, CS intensity was varied and the US intensity was lower than that used in Experiment I and II. Avoidance of 21- and 90-day-old rats was higher with a more intense CS, but 21-day-olds were still lower than adults. Avoidance of 17-day-old rats was not affected by CS intensity.     

Latent inhibition of conditioned odor potentiation of startle: a developmental analysis

We conducted a two-part study of age and latent inhibition in the rat. In the first part of the study, rats given odor-shock pairings at 23 or 75 days of age exhibited a potentiated startle response in the presence of the odor the following day. This effect did not occur in rats trained at 16 or 20 days of age. Odor pre-exposure on the day prior to conditioning markedly reduced the odor potentiation of startle effect in 23- and 75-day-old rats but had no effect in 16 and 20-day-olds. In the second part of the study, rats were pre-exposed to the odor at 16 or 20 days of age and then conditioned at 23 days of age. When tested the day after conditioning, these pre-exposed rats exhibited a disruption in the odor potentiation of startle effect. We compare our results with other studies of latent inhibition, and with recent studies on whether conditioned responses are appropriate to the animal's age at training or their age at test.     

Differential effect of free intake versus oral perfusion of sucrose in conditioned taste aversion in rats.

Five experiments were designed to investigate LiCl-induced conditioned taste aversion (CTA) obtained in rats whether after free intake of a sucrose solution (active mode) or after forced administration through an intraoral cannula (passive mode). It was found in Experiment 1 that actively conditioned rats showed a slower extinction rate as revealed by repeated two-bottle tests (active testing) as opposed to passively conditioned ones. As these rats underwent a mode change between conditioning and testing, the differential extinction rate might have arisen from this change inducing a generalization decrement effect or acting as a contextual shift. In Experiment 2, no evidence for any generalization decrement was found. The possibility that the mode of sucrose delivery could have contextual properties in CTA through a "renewal test" after extinction and a latent inhibition experiment was further tested in Experiments 3 and 4. When active testing followed passive extinction, a CTA was afresh obtained in rats actively conditioned in active conditions. Latent inhibition was attenuated in rats preexposed in passive conditions and conditioned in active conditions (i.e., when a shift in the drinking mode occurred between preexposure and conditioning). In Experiment 5, intraoral perfusion was used in both groups. The active subjects had to nose poke for intraoral administration of sucrose. The yoked control passive subjects received simultaneously the same amount of sucrose. The levels of CTA differed also from the actively to the passively conditioned subjects. Results are discussed in terms of free intake activity acting as a contextual modulator of CTA.     

Age-related differences in avoidance behavior in rats following CS preexposure

Weanling and adult rats were exposed to either 0 or 10 conditioned stimulus (CS) presentations prior to 1-way active-avoidance (AA) training. Although CS exposure retarded avoidance acquisition in the adults, it produced no effect in the pups during avoidance learning. Neither adult nor young rats demonstrated preexposure effects in extinction. A general extinction analysis showed that pups had less resistance to extinction than the adults, despite a comparable avoidance learning criterion between age groups. The lack of preexposure influences on performance by the pups was compared to previous findings of response inhibitory deficits in immature rats. The results were considered in light of selective attention interpretations of latent inhibition.     

Acquisition and retention of separate elements of a conditioned olfactory discrimination in preweanling rats

Acquisition and retention of separate elements of an olfactory discrimination were tested in 15- and 20-day-old preweanling rats. Four or 8 conditioning trials were given in Experiment 1. Each rat was presented one odor always followed by footshock (CS+) and another never paired with footshock (CS-). Conditioning to both stimuli was assessed through 3 types of olfactory preference tests involving comparison between CS+ and a novel odor, CS- and a novel odor, or CS+ and CS-. The results indicated that for 15- and 20-day-olds, both stimuli become excitatory early in training; further conditioning trials diminished the excitation previously accrued to the CS-, and the olfactory discrimination became apparent. When levels of conditioning were equated, retention was tested after intervals of 4 min, 3 days, or 8 days (Exp. 2). Rate of forgetting was more rapid for the 15-day-olds, but both ages of subjects showed similar patterns of forgetting, which included a progressive decrease in the aversion to the CS+ but an increase in aversion to the CS-.     

Function of ECS as a cue in retrograde amnesia in the rat

Two experiments were performed with rats to examine whether electroconvulsive shock (ECS), which is known to produce retrograde amnesia (RA), would serve as a dominant cue in the training trial. In Experiment I, after 6, 1, or 0 ECS preexposures , rats were received ECS immediately following one-trial passive avoidance training in a step through apparatus. Twenty-four h later, six ECS preexposure group showed a higher level of retention performance. Thus, the effects of ECS on RA were shown to be attenuated by the preexposure to ECS. In Experiment II, it was shown that ECS acquired a considerable amount of cue value which might produce a conditioned suppression on an off-the-baseline type procedure. These results were interpreted as that RA phenomena could be considered as a sort of retroactive conditioning where ECS served as a CS.