Salience modulation and associative inhibition interaction: Short but not long exposure to similar stimuli protects the salience of the unique elements

In three experiments, rats were given preexposure to two similar flavour compounds, AX and BX. Following preexposure, conditioning trials took place in which AX was paired with an illness-induced unconditioned stimulus. Animals that were given short alternated preexposure to AX and BX, showed higher generalization of conditioned aversion to AX to a new compound, AN, than animals that were given blocked preexposure (short and long) and long alternated preexposure (Experiments 1 and 2); and showed less preference for A when they were given a choice between A and X (Experiment 3). These results have been taken to indicate that the salience of the A element is well preserved after short alternated preexposure, but declines when preexposure goes on for some more trials. The results reported support the notion that perceptual learning is a multi-determined phenomenon that depends on salience modulation processes after relatively short preexposure, and on an associative inhibition mechanism after prolonged preexposure.     

Dissociation between the Espinet and perceptual learning effects in flavour aversion conditioning

In three experiments rats were given pre-exposure to two compound flavours, AX and BX, the two compounds being presented for some subjects on alternate trials (the intermixed schedule) and, for others, in separate blocks of trials (the blocked schedule). After aversion conditioning with A (in Experiments 1 and 2), the inhibitory properties of B were tested using both retardation (Experiment 1) and summation tests (Experiment 2). The results failed to support the proposal [Anim. Learn. Behav. 23 (1995) 361] that B should acquire inhibitory properties in the intermixed condition (the "Espinet effect"). Experiment 3 demonstrated that generalisation to BX after conditioning with AX was attenuated by intermixed pre-exposure (a perceptual learning effect). This pattern of results challenges the hypothesis that inhibitory learning during intermixed pre-exposure to AX and BX can account for both the Espinet and the perceptual learning effects.     

Blocked and test-stimulus exposure effects in perceptual learning re-examined

Three experiments re-examined the effects of blocked or alternated exposure to the conditioning and test stimuli and the effect of simple exposure to the test stimulus, on stimulus generalization. In all experiments rats received conditioning where a compound flavor, AX, was paired with LiCl-induced illness. All rats were tested for generalization with another flavor, BX. In Experiment 1, rats that received alternating exposure to the two flavor compounds, AX and BX, prior to conditioning showed less generalization to BX than rats that received no exposure. Exposure to BX or AX alone was also somewhat effective in reducing generalization. In Experiment 2 blocked exposure to AX and BX prior to conditioning was effective in reducing generalization, as was alternated exposure, and extended exposure to BX was more effective than the other procedures. In Experiment 3, exposure to X alone prior to conditioning produced generalization equal to that produced by alternated or blocked exposure and replicated the effect of extended exposure to BX found in the previous experiment. The relevance of the results to the theories proposed by McLaren and Macintosh [Anim. Learn. Behav. 28 (2000) 211] and Hall [Q. J. Exp. Psychol. B 56 (2003) 43] is discussed.     

An assessment of context-specificity of the CS-preexposure effect in Pavlovian excitatory and inhibitory conditioning

Non-reinforced preexposure to a to-be-conditioned stimulus (CS) results in retarded development of conditioned excitation and inhibition. In a magazine-approach preparation in rats, we explored the role of background context on this CS-preexposure effect by changing contexts after the preexposure treatment. Experiment 1 demonstrated with a typical three-group design that changing background contexts attenuated the CS-preexposure effect in conditioned excitation. Experiment 2 employed the identical design except that conditioned inhibition was the target of study. Preexposure to stimulus X retarded subsequent differentiation of responding to reinforced A trials and non-reinforced AX trials, suggesting that CS-preexposure retarded development of inhibitory conditioning. However, changing contexts did not attenuate the preexposure effect. We discuss these results in the framework of the extended comparator hypothesis.     

The contribution of latent inhibition to reduced generalization after pre-exposure to the test stimulus

Two experiments assessed the contribution of latent inhibition to the generalization-reducing effects of pre-exposure to the test stimulus using a taste aversion procedure in rats. In both experiments, lithium chloride induced illness was paired with a flavor compound (AX) of either salt or sugar (A or B) and hydrochloric acid (X). Generalization of the resulting aversion to a test compound (BX), was assessed after varying pre-exposure to BX, X, and B. Experiment 1 showed that generalization to BX was less when BX itself had been exposed than equivalent pre-exposure to either B and X separately or to B and a new compound (CX). Experiment 2 showed that levels of generalization varied directly as a function of the amount of pre-exposure to BX. The findings show that latent inhibition alone cannot account for the generalization-reducing effect of pre-exposure to BX.     

The influence of comparison between similar stimuli on the effectiveness of their unique features

Four groups of rats received stimulus pre-exposure under conditions intended to produce different opportunities for stimulus comparison to occur. Groups AX/BX-L and AX/BX-S received alternating presentations of two compound flavors (AX and BX); the interval between these presentations was long (24 h) for group AX/BX-L, and short (5 min) for group AX/BX-S. Groups AX-L and AX-S matched groups AX/BX-L and AX/BX-S in their pre-exposure conditions except that they received presentations of water rather than presentations of BX. The effective salience of one of the unique stimulus features (A) was then assessed by using this flavor as a conditioned stimulus in a flavor-aversion procedure. It was found that aversion to A was learned about more readily after pre-exposure to AX and BX than after pre-exposure just to AX. However, there was no indication that the rate of conditioning to A was affected by the temporal interval between the presentations of AX and BX. These findings challenge the notion that stimulus comparison engages a process responsible for an increase in the salience of the unique stimulus features, but can be accommodated by the salience modulation mechanism proposed by Hall [Hall, G., 2003. Learned changes in the sensitivity of stimulus representations: associative and nonassociative mechanisms. Q. J. Exp. Psychol. 56, 43-55].     

An examination of the effectiveness of inflation and deflation treatments in detecting within-compound learning of a taste aversion

Two conditioned taste aversion experiments with rats assessed the relative effectiveness in providing evidence of within-compound learning of different procedures that involve the initial compound presentation of two stimuli, A and X, with the unconditioned stimulus (i.e., AX+). In Experiment 1, following a single AX+ trial, groups A+ and B+ received an additional conditioning trial (i.e., inflation treatment) with A and B, respectively, whereas group A- received an extinction trial (i.e., deflation treatment) with A. The results showed a reduction in the aversion elicited by the target stimulus, X, in group A- relative to both groups A+ and B+, which did not differ. Experiment 2 further investigated the failure of group A+ to increase the aversion to X relative to control group B+ by pairing A or B with either the same unconditioned stimulus that was previously paired with AX (groups A+ and B+) or with a stronger unconditioned stimulus (groups A* and B*). The results showed increased aversion to X in group A* relative to group B*, but not in group A+ relative to group B+. These results are interpreted as indicative of extinction of the within-compound association during the treatment with A, which could likely impair the detection of within-compound learning following an inflation, but not a deflation treatment.     

Effects of context novelty vs. familiarity on latent inhibition with a conditioned taste aversion procedure

The latent inhibition phenomenon is observed when a conditioned stimulus is preexposed without any consequence before conditioning. The result of this manipulation is a reduction in conditioned response intensity to such a stimulus. In this study, we analyse the role of context novelty/familiarity on LI modulation by changing the context using a three-stage conditioned taste aversion procedure. Experiment 1 revealed that, similar to other learning procedures, a context change between preexposure and conditioning/testing (but not between preexposure/conditioning and testing) resulted in LI attenuation when the experimental contexts were novel. Experiment 2, using animals’ home cages as one of the contexts, revealed a different pattern of results, with an unexpected increase in LI magnitude when the context change was introduced between conditioning and test stages. The Schmajuk et al. (1996) computational model explains these results in terms of the increased novelty of the conditioned stimulus during preexposure, conditioning, and testing.     

Perceptual learning in an appetitive Pavlovian procedure: Analysis of the effectiveness of the common element

Non-reinforced preexposure to two stimuli often enhances discrimination between them. Analyses of this perceptual learning phenomenon have mainly focused on the role played by the distinctive stimulus features; this study examined the contribution of the non-distinctive common elements. A standard appetitive Pavlovian procedure was used. Rats received two different schedules of exposure - alternated or blocked - to two compound auditory stimuli, AX and BX. In Experiment 1 a generalization test to BX that followed conditioning to AX showed that animals responded less, and hence discriminated better, following alternated exposure, thus extending the generality of this perceptual learning effect to standard appetitive Pavlovian procedures. The degree to which the common element X was mediating this effect was explored in the next three experiments. Experiment 2 assessed the effectiveness of X following conditioning to AX. Experiment 3 explored X's effectiveness throughout extensive conditioning to X. Experiment 4 tested the ability of X to overshadow a novel stimulus Y. The results were consistent with the suggestion that alternated preexposure can reduce the relative effectiveness of the common element.     

Effects of an extinguished CS on competition with another CS

Three experiments were conducted using a conditioned taste aversion procedure with rats to examine the effect of nonreinforced presentations of a conditioned stimulus (CS) on its ability to compete with a target stimulus for manifest conditioned responding. Two CSs (A and B) were presented in a serial compound and then paired with the unconditioned stimulus. CS A was first paired with the US and then presented without the US (i.e., extinction) prior to reinforced presentation of the AB compound. Experiment 1 showed that A was poor at competing with B for conditioned responding when given conditioning and extinction prior to reinforcement of AB relative to a group that received both A and B for the first time during compound conditioning. That is, an extinguished A stimulus allowed greater manifest acquisition to B. Experiment 2 found that extinction treatment produced a poor CR to the pretrained and extinguished CS itself following compound conditioning. Experiment 3 found that interposing a retention interval after extinction of A and prior to compound conditioning enhanced A's ability to compete with B. The results of these experiments are discussed with regard to different theories of extinction and associative competition.     

Preexposure to the stimulus elements,but not training to detect them,retards human odour-taste learning

Odours are judged to smell sweeter following simultaneous oral pairings with the tastant sucrose and sourer after parings with the tastant citric acid. This effect may result from human participants perceiving and encoding a unitary odour-taste percept. This study examined two factors thought likely to disrupt such encoding; (a) preexposure to the mixture elements and (b) training to spot the elements of taste-odour mixtures. Half of the participants were trained to identify tastes and smells and half received no training. All participants were preexposed to two odours (A, B) and two tastes (X, Y), followed by pairings of these stimuli (AX, BY) and then by pairings between two non-preexposed odours and the same tastes (CX, DY). This process was then repeated on a second session. Odour-taste learning was retarded following preexposure, but was unaffected by training. These findings suggest; (1) that odour-taste mixtures may be cognitively impenetrable and (2) that preexposure leads to encoding of A and B, which are then resistant to interference when further pairings are presented (i.e. AX, BY).     

An optimized method for detecting gamma-H2AX in blood cells reveals a significant interindividual variation in the gamma-H2AX response among humans

Phosphorylation of histone H2AX on serine 139 (gamma-H2AX, γH2AX) occurs at sites flanking DNA double-strand breaks (DSBs) and can provide a measure of the number of DSBs within a cell. Here we describe a rapid and simple flow-cytometry-based method, optimized to measure gamma-H2AX in non-fixed peripheral blood cells. No DSB induced signal was observed in H2AX−/− cells indicating that our FACS method specifically recognized gamma-H2AX accumulation. The gamma-H2AX assay was capable of detecting DNA damage at levels 100-fold below the detection limit of the alkaline comet assay. The gamma-H2AX signal was quantitative with a linear increase of the gamma-H2AX signal over two orders of magnitude. We found that all nucleated blood cell types examined, including the short-lived neutrophils induce gamma-H2AX in response to DSBs. Interindividual difference in the gamma-H2AX signal in response to ionizing radiation and the DSB-inducing drug calicheamicin was almost 2-fold in blood cells from patients, indicating that the amount of gamma-H2AX produced in response to a given dose of radiation varies significantly in the human population. This simple method could be used to monitor response to radiation or DNA-damaging drugs.     

Blocking of conditioned taste avoidance induced by wheel running

In Experiment 1, compared to non-reinforced presentation of a food stimulus (A → no US), the association of a food stimulus with wheel running (A → US) blocked subsequent avoidance of a distinctive flavor (X), when both the food and flavor were followed by wheel running (AX → US). Experiment 2 replicated and extended the blocking effect, demonstrating that the amount of avoidance of X after AX → wheel training depended on the correlation between A-alone trials and wheel running—the predictiveness of the A stimulus. The present study is the first to demonstrate associative blocking of conditioned taste avoidance (CTA) induced by wheel running and strongly implicates associative learning as the basis for this kind of avoidance.     

Pavlovian biconditional discrimination learning in the C57BL/6J mouse

Four experiments using mice examined acquisition of Pavlovian biconditional discriminations in which two stimulus compounds were paired with food (AX+ and BY+) and two were not (AY- and BX-). Temporally asynchronous compounds were generated by using contextual stimuli (Experiment 1) and 15-s discrete visual cues (Experiments 2A, 2B and 3) to disambiguate when embedded noise or tone stimuli would be paired with food. When food pellets followed both reinforced compounds, successful acquisition was obtained in Experiment 1 but not in Experiments 2A and 2B even though the order of trials was modeled after that used in Experiment 1. However, when differential outcomes followed the reinforced compounds in Experiment 3, acquisition was obtained with discrete cue stimulus compounds. The implications of these results for modulatory models of conditional discrimination learning in animals are discussed.     

Latent inhibition as a function of CS intensity in taste aversion learning

An experiment is reported in which the relationship between the intensity of a preexposed stimulus and latent inhibition was investigated, using the taste aversion learning paradigm in rats. Two concentrations of a saline solution (high, 1%; and low, 0.25%) were used during preexposure and conditioning phases in a factorial design. Two control conditions without preexposure were added, one for each stimulus concentration during conditioning. The known effect of conditioned stimulus (CS) intensity during conditioning was confirmed: the more concentrated the solution used in conditioning, the higher the acquisition rate. A direct relationship was observed between the CS intensity used during preexposure and the latent inhibition effect: the more concentrated the solution during preexposure, the lower the acquisition rate of conditioning. The implications of these results for latent inhibition theories are considered.     

ADP‐ribosylation of histone variant H2AX promotes base excision repair

Optimal DNA damage response is associated with ADP‐ribosylation of histones. However, the underlying molecular mechanism of DNA damage‐induced histone ADP‐ribosylation remains elusive. Herein, using unbiased mass spectrometry, we identify that glutamate residue 141 (E141) of variant histone H2AX is ADP‐ribosylated following oxidative DNA damage. In‐depth studies performed with wild‐type H2AX and the ADP‐ribosylation‐deficient E141A mutant suggest that H2AX ADP‐ribosylation plays a critical role in base excision repair (BER). Mechanistically, ADP‐ribosylation on E141 mediates the recruitment of Neil3 glycosylase to the sites of DNA damage for BER. Moreover, loss of this ADP‐ribosylation enhances serine‐139 phosphorylation of H2AX (γH2AX) upon oxidative DNA damage and erroneously causes the accumulation of DNA double‐strand break (DSB) response factors. Taken together, these results reveal that H2AX ADP‐ribosylation not only facilitates BER repair, but also suppresses the γH2AX‐mediated DSB response.     

Proportion of odorants impacts the configural versus elemental perception of a binary blending mixture in newborn rabbits

Processing of odor mixtures by neonates is weakly understood. Previous studies showed that a binary mixture of ethyl isobutyrate/ethyl maltol (odorants A/B) blends in newborn rabbits at the 30/70 ratio: Pups would perceive a configural odor in addition to the components' odors. Here, we investigated whether the emergence of this additional odor in AB is determined by specific ratio(s) of A and B. To that goal, we tested whether pups discriminated between AB mixtures with lower (A(-)B, 8/92 ratio) or higher (A(+)B, 68/32) proportion of A. In Experiment 1, pups conditioned to A (or B) responded to A(-)B and A(+)B but not to AB. In Experiment 2, pups responded to A(-)B after learning of A(-) (and to A(+)B after learning of A(+)) but not to AB. In Experiment 3, after conditioning to A(-)B pups responded to A(-) and B (and to A(+) and B after learning of A(+)B) but not or less to AB. In Experiment 4, pups responded to A(-)B and A(+)B after conditioning to AB. These results confirm the configural perception of certain odor mixtures by young organisms and reveal that the proportion of components is a key factor influencing their coding, recognition, and discrimination of complex stimuli.     

Stimulus comparison in perceptual learning: roles of sensory preconditioning and latent inhibition

Rats were given exposure to a compound flavour (AX) and to one element of that compound (X). Two drinking tubes were made available to the rat on each exposure trial. For group concurrent (CNC) one tube contained AX and the other X. For groups alternating (ALT) and blocked (BLK), however, both tubes contained the same flavour (AX or X). Group ALT received AX and X on alternate trials; group BLK received AX in the first block of trials and X on the second, or vice versa. After an aversion had been established to X the groups were tested with AX. It was found that group ALT showed less generalization from X to AX than did group BLK. This difference was not accompanied by a parallel difference in the level of conditioning to X. However, group CNC showed both stronger conditioning to X and greater generalization from X to AX than groups ALT and BLK. Implications for the role of stimulus comparison in the perceptual learning effect are discussed.     

Plasma luteinizing hormone and testosterone concentrations in different breeds of young beef bulls in the tropics

Plasma concentrations of luteinizing hormone (LH) and testosterone were measured at 3, 8, and 11 months of age in 48 Africander cross (AX), 24 Brahman cross (BX), 21 Hereford-Shorthorn, selected (HSS) and 14 Hereford-Shorthorn, random-bred (HSR) bulls. In all breeds plasma LH was lower (P less than 0.01) at 8 months (1.7 ng/ml) than at 3 months (2.6 ng/ml) or at 11 months (2.6 ng/ml). Over all ages there were no differences among breeds in mean plasma LH (AX 2.4, BX 2.4, HSS 1.8, HSR 2.2 ng/ml) and no breed X age interactions. In contrast, plasma testosterone increased significantly (P less than 0.01) with age at a faster rate in the AX breed, resulting in a significant (P less than 0.05) breed X age interaction. Testosterone concentrations, though similar among breeds at 3 months of age (0.45 ng/ml), were much higher (P less than 0.01) by 11 months in AX (2.56 ng/ml) than in BX (1.30 ng/ml), HSS (0.78 ng/ml) or HSR (0.66 ng/ml) bulls. Although LH did not differ among the breeds studied, the more pronounced increase in testosterone with age in the Africander cross bulls is consistent with the higher level of fertility commonly observed in this breed when compared to Brahman cross and Hereford-Shorthorn breeds during natural mating in Queensland.     

Repeated administration of LiCl produces an unconditioned stimulus preexposure effect in backward excitatory CTA but not habituation of the unconditioned increment in neophobia

In one experiment using conditioned taste aversion and the unconditioned stimulus (US) preexposure procedure, one group of rats was given LiCl exposure for 3 days, whereas two other groups received saline. Following this phase, all groups were given a novel flavour (saccharine) to drink following either LiCl (group preexposed and one of the control groups) or saline injections (the remaining control group) and the consumption of the flavour was assessed. After this neophobia test, the acquired saccharine aversion was evaluated. The results show that three LiCl injections are enough to produce a US preexposure effect on backward excitatory taste aversion conditioning, whereas this number of injections procedure does not produce habituation of the increment in neophobia, an unconditioned response to the LiCl. The results are discussed taking into account different mechanisms involved in US preexposure effect.