Attitudes to the use of animals in biomedical research: Effects of stigma and selected research project summaries.

Three groups of participants (largely recruited from the UK) completed a survey to examine attitudes to the use of animals in biomedical research, after reading the lay (N = 182) or technical (N = 201) summary of a research project, or no summary (N = 215). They then completed a survey comprising the animal attitude (AAS), animal purpose (APQ), belief in animal mind (BAM) and empathy quotient (EQ) scales. The APQ was adapted to assess attitudes towards the use of animals for research into disorders selected to be perceived as controllable and so 'blameworthy' and potentially stigmatised (addiction and obesity) and 'psychological' (schizophrenia and addiction) versus 'physical' (cardiovascular disease and obesity), across selected species (rats, mice, fish pigs and monkeys). Thus, the APQ was used to examine how the effects of perceived controllability and the nature of the disorder affected attitudes to animal use, in different species and in the three summary groups. As expected, attitudes to animal use as measured by the AAS and the APQ (total) correlated positively with BAM and EQ scores, consistent with the assumption that the scales all measured pro-welfare attitudes. Participants in the two research summary groups did not differentiate the use of rats, mice and fish (or fish and pigs in the technical summary group), whereas all species were differentiated in the no summary group. Participants given the lay summary were as concerned about the use of animals for schizophrenia as for addiction research. APQ ratings otherwise indicated more concern for animals used for addiction research (and for obesity compared to cardiovascular disease in all summary groups). Therefore, the information provided by a research project summary influenced attitudes to use of animals in biomedical research. However, there was no overall increase in agreement with animal use in either of the summary groups.

Time or place? Dissociation between object-in-place and relative recency in young APPswe/PS1dE9 mice.

This study tests the predictions of a novel analysis of recognition memory based on a theory of associative learning, according to which recognition comprises two independent underlying processes, one relying on the to-be-recognized item having been experienced recently (self-generated priming), and the other on it being predicted by some other stimulus (retrieval-generated priming). A single experiment examined recognition performance in the amyloid precursor protein (APP)swe/PS1dE9 (APP/PS1) mouse, a double-transgenic model of Alzheimer's disease (AD), and wild type (WT) littermates. Performance on two variants of the spontaneous object recognition (SOR) was compared in 5-month-old APPswe/PS1dE9 (APP/PS1) mice, a double-transgenic model of AD, and their WT littermates, using junk objects. In the relative recency task animals were exposed to object A, and then object B, followed by a test with both A and B. In the object-in-place task the mice were exposed to both A and B, and then tested with two copies of A, occupying the same positions as the preeexposed objects. The WT mice showed a preference for exploring the first-presented object A in the relative recency task, and the copy of A in the "wrong" position (i.e., the one placed where B had been during the preexposure phase) in the object-in-place task. The APP/PS1 mice performed like the WT mice in the relative recency task, but showed a selective impairment in the object-in-place task. We interpret these findings in terms of-Wagner's (Information processing in animals: Memory Mechanisms, 1981, Erlbaum) theory of associative learning, sometimes opponent process (SOP), as a selective deficit in retrieval-generated priming. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

An associative analysis of recognition memory: Relative recency effects in an eye-tracking paradigm.

We report 2 eye-tracking experiments with human variants of 2 rodent recognition memory tasks, relative recency and object-in-place. In Experiment 1 participants were sequentially exposed to 2 images, A then B, presented on a computer display. When subsequently tested with both images, participants biased looking toward the first-presented image A: the relative recency effect. When contextual stimuli x and y, respectively, accompanied A and B in the exposure phase (xA, yB), the recency effect was greater when y was present at test, than when x was present. In Experiment 2 participants viewed 2 identical presentations of a 4-image array, ABCD, followed by a test with the same array, but in which one of the pairs of stimuli exchanged position (BACD or ABDC). Participants looked preferentially at the displaced stimulus pair: the object-in-place effect. Three further conditions replicated Experiment 1's findings: 2 pairs of images were presented one after the other (AB followed by CD); on a test with AB and CD, relative recency was again evident as preferential looking at AB. Moreover, this effect was greater when the positions of the first-presented A and B were exchanged between exposure and test (BACD), compared with when the positions of second-presented C and D were exchanged (ABDC). The results were interpreted within the theoretical framework of the Sometime Opponent Process model of associative learning (Wagner, 1981). (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Timing impairments in early Alzheimer's disease: Evidence from a mouse model.

A key characteristic of Alzheimer's disease (AD) is loss of episodic memory-memory for what happened, where and when; this final aspect-timing-is the focus of the present article. Although timing deficits have been reported in AD patients, few parallel studies have been performed in animals, compromising the translational potential of these findings. We looked for timing impairments in the APPswe/PS1dE9 mouse model of AD at 4-5 months of age, before significant plaques have developed. In Experiments 1 and 2a mice were trained with auditory stimuli that were followed by food, either immediately (delay stimulus; Experiments 1 and 2a) or after a short interval (trace stimulus; Experiment 1). In Experiment 1 APPswe/PS1dEdE9 mice conditioned normally, but showed more variable timing of the delay-conditioned cue. Experiment 2 examined timing of two delay-conditioned CSs, with Experiment 2a using mice 4-5 months old, and Experiment 2b mice at 6-8 months. With the longer conditional stimulus (CS) the transgenic mice showed both more variable timing and earlier timed peak responding than wild-type mice; these effects were not influenced by age. Our results bear similarity to those seen in AD patients, raising the possibility that they have diagnostic potential. They also resemble deficits in animals with dorsal hippocampal lesions, suggesting that they could be mediated by this area. Activated microglia, a component of the immune response thought to be driven by the elevated levels of ß-amyloid, were elevated in both dentate gyrus and striatum of young transgenic mice, providing some support for this proposal. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Under the influence of the environment: Children's responding invigorated and biased by predictive cues.

Cues that signal motivationally significant consequences can elevate responding and bias choice. A task known as Pavlovian-to-instrumental transfer (PIT) has been used to assess the influence of these cues on independently trained responses and to study the effect of drug-related and food-related cues on behavior in adult populations, but it has not yet been employed in children. This study aimed to develop a simple computer task to study PIT in children. Participants, aged 7-11 years, observed a screen in which different pairings of distinct cartoon images and specific outcomes were presented (images of foods and drinks in Experiment 1 and images of pets in Experiment 2). After this, the participants pressed two keys, each consistently reinforced with one of the two outcomes. Finally, the children pressed both keys in the absence of any outcome, and each cartoon image was presented periodically so that the effect of these cues on behavior could be measured. Experiment 1 showed that the cartoons' presentations biased responding toward the key that was trained with the same outcome as the cartoon being presented, that is, outcome-specific PIT. Experiment 2 replicated this finding and also showed that a cartoon trained with an outcome different from that reinforcing the responses elevated performance of both responses relative to a cartoon that was not paired with any outcome in training, that is, general PIT. These findings are consistent with those reported in the adult population and might be a useful tool to study the early development of maladaptive behaviors.

The effect of conditioned inhibitors and preexposed cues on the outcome-specific Pavlovian-to-instrumental transfer effect in humans.

Using a human Pavlovian-to-instrumental transfer (PIT) task, Alarcón and Bonardi showed that the selective elevation of instrumental responding produced by excitatory transfer cues was reduced when these cues were presented with a conditioned inhibitor (CI), relative to a control cue that was simply preexposed. However, previous research has shown that preexposed cues might also acquire inhibitor-like properties. This study aimed to contrast the inhibitory properties of CIs and preexposed cues, using novel stimuli as controls, in summation and PIT tests. Participants were trained to perform two actions, each reinforced with a distinct outcome (O1 or O2). Two images were trained as CIs, each signalling the absence of one of the outcomes, by presenting them with a cue that was otherwise followed by that outcome (e.g., A→O1, AI→no O1). In contrast, the preexposed cues were simply presented in the absence of the outcomes. In the summation test, participants rated the likelihood of the outcomes in the presence of two independently trained excitatory cues, each presented with a CI, a preexposed cue, or a novel stimulus. Similarly, in the PIT test, participants performed both actions in the presence and absence of these compounds. In the summation test, the CIs and the preexposed cues reduced participants' expectations of the outcomes more than the novel stimuli. However, in the PIT test, only the CIs reduced the selective elevation of responding produced by the transfer cues. These results might reflect distinct properties of stimuli trained as CIs and those simply preexposed.

The effects of stimulus distribution form during trace conditioning.

Three experiments examined the effect of distribution form of the trace interval on trace conditioning. In Experiments 1 and 2, two groups of rats were conditioned to a fixed-duration conditioned stimulus (CS) in a trace interval procedure; rats in Group Fix received a fixed-duration trace interval, whereas for rats in Group Var the trace interval was of variable duration. Responding during the CS was higher in Group Var than in Group Fix, whereas during the trace interval this difference in responding reversed-Group Fix showed higher response rates than Group Var. Experiment 3 examined whether the greater response rate observed during the CS in Group Var was due to a performance effect or the acquisition of greater associative strength by the CS. Following trace conditioning, the rats from Experiment 1 underwent a second phase of delay conditioning with the same CS; a 5-s auditory stimulus was presented in compound with the last 5 s of the 15-s CS, and the unconditioned stimulus (US) was delivered at the offset of the CSs. On test with the auditory stimulus alone, subjects in Group Var showed lower response rates during the auditory stimulus than subjects in Group Fix. We interpreted these findings as evidence that the superior responding in Group Var during the CS was a result of it acquiring greater associative strength than in Group Fix.

Associative mechanisms involved in specific Pavlovian-to-instrumental transfer in human learning tasks.

Four experiments compared the effect of forward and backward conditioning procedures on the ability of conditioned stimuli (CS) to elevate instrumental responding in a Pavlovian-to-instrumental transfer (PIT) task. Two responses were each trained with one distinct outcome (R1->O1, R2->O2), either concurrently (Experiment 1) or separately (Experiments 2, 3 and 4). Then, in Experiments 1 and 2, four CSs were either followed or preceded by one outcome (A->O1, B->O2, O1->C, O2->D). In Experiment 3, each CS was preceded and followed by an outcome: for one group of participants, both outcomes were identical (e.g., O1->A->O1, O2->B->O2), but for the other, they were different (e.g., O1->A->O2, O2->B->O1). In Experiment 4, two CSs were preceded and followed by identical outcomes, and two CSs by different outcomes. In the PIT tests, participants performed R1 and R2 in the presence and absence of the CSs. In Experiments 1 and 2, only the CSs followed by outcomes in Pavlovian training elevated responding. In Experiments 3 and 4, all the CSs elevated responding but based on the outcome that followed them in training. These results support the stimulus-outcome-response (S-O-R) mechanism of specific PIT, according to which CSs elevate responding via activation of its associated outcome representation.

Blocking by fixed and variable stimuli: Effects of stimulus distribution on blocking.

An experiment with rats compared the ability of fixed and variable duration cues to produce blocking. Rats in group B (Blocking) were trained that both fixed- (F) and variable- (V) duration cues would be followed by food delivery. In a subsequent training stage F and V continued to be reinforced, but F was accompanied by X, and V by Y. In the test phase responding to X and Y was examined. Control group O (Overshadowing) received identical treatment, except that F and V were nonreinforced in the first training stage. In group B there was evidence for blocking, but only of X, which had been conditioned in compound with the fixed-duration F; there was no evidence for blocking of Y, which had been conditioned in compound with the variable-duration V. It is suggested that this result may occur because fixed cues reach a higher, more stable asymptote of associative strength than do their variable equivalents.

Can existing associative principles explain occasion setting? Some old ideas and some new data.

Since occasion setting was identified as a type of learning independent of 'simple' associative processes, a great deal of research has explored how occasion setters are established and operate. Initial theories suggested that they exert hierarchical control over a target CS→US association, facilitating the ease with which a CS can activate the US representation and elicit the CR. Later approaches proposed that occasion setting arises from an association between a configural cue, formed from the conjunction of the occasion setter and CS, and the US. The former solution requires the associative principles dictating how stimuli interact to be modified, while the latter does not. The history of this theoretical distinction, and evidence relating to it, will be briefly reviewed and some novel data presented. In summary, although the contribution of configural processes to learning phenomena is not in doubt, configural theories must make many assumptions to accommodate the existing data, and there are certain classes of evidence that they are logically unable to explain. Our contention is therefore that some kind of hierarchical process is required to explain occasion-setting effects.

Deficits in object-in-place but not relative recency performance in the APPswe/PS1dE9 mouse model of Alzheimer's disease: Implications for object recognition.

Performance was examined on three variants of the spontaneous object recognition (SOR) task, in 5-month old APPswe/PS1dE9 mice and wild-type littermate controls. A deficit was observed in an object-in-place (OIP) task, in which mice are preexposed to four different objects in specific locations, and then at test two of the objects swap locations (Experiment 2). Typically more exploration is seen of the objects which have switched location, which is taken as evidence of a retrieval-generated priming mechanism. However, no significant transgenic deficit was found in a relative recency (RR) task (Experiment 1), in which mice are exposed to two different objects in two separate sample phases, and then tested with both objects. Typically more exploration of the first-presented object is observed, which is taken as evidence of a self-generated priming mechanism. Nor was there any impairment in the simplest variant, the spontaneous object recognition (SOR) task, in which mice are preexposed to one object and then tested with the familiar and a novel object. This was true regardless of whether the sample-test interval was 5min (Experiment 1) or 24h (Experiments 1 and 2). It is argued that SOR performance depends on retrieval-generated priming as well as self-generated priming, and our preliminary evidence suggests that the retrieval-generated priming process is especially impaired in these young transgenic animals.

Learning about the CS during latent inhibition: Preexposure enhances temporal control.

In 3 experiments, rats were given nonreinforced preexposure to an auditory stimulus, after which this stimulus and a second, novel cue were paired with food. Lower rates of conditioned responding were observed to the preexposed stimulus across the 3 experiments, indicative of latent inhibition. The degree to which animals used these cues to time the occurrence of food delivery was also examined. Paradoxically, the response slopes-indicating the rate of increase in responding over the course of the conditioned stimulus-were greater for the preexposed than for the novel cues, consistent with the suggestion that the preexposed stimulus exerted greater temporal control. Moreover, this was the case irrespective of whether the duration of the cue during preexposure differed from that during conditioning. These results suggest that although conditioned stimulus preexposure retards conditioning, it may enhance timing. The findings are discussed in terms of current models of conditioning and timing.

The effect of conditioned inhibition on the specific Pavlovian-instrumental transfer effect.

Four experiments examined the effect of Pavlovian conditioned inhibition on specific Pavlovian-instrumental transfer (PIT) in human participants. The task comprised an instrumental phase in which 2 responses (R1, R2) were each paired with 1 of 2 outcomes (O1, O2: R1→O1, R2→O2), and a Pavlovian phase, in which 2 conditioned stimuli (CSs), CS1 and CS2 each signaled 1 of the 2 outcomes (CS1→O1, CS2→O2). In Experiments 1-2 a conditioned inhibitor, X, predicted the omission of 1 of the outcomes (e.g., CS1→O1, CS1X→nothing). In a subsequent test, performance of R1 and R2 was examined in the presence of CS1 and CS2. A specific PIT effect was observed: R1 was performed more than R2 during CS1, and R2 more than R1 during CS2. This PIT effect was significantly reduced by the presence of the inhibitor X in Experiment 1, in which the Pavlovian phase followed the instrumental phase, and in Experiment 2 in which it preceded it. No such effect was observed when X was presented in the absence of any expectation of the outcomes during the PIT test (Experiment 3a), or when X was trained as a signal for an alternative outcome (Experiment 3b). These results are consistent with the suggestion that the specific PIT effect occurs through a stimulus-outcome-response (S-O-R) mechanism, according to which the CS evokes a representation of the outcome which in turn elicits the response (e.g., CS1→O1→R1). The conditioned inhibitor suppresses performance of the response by suppressing activation of the outcome representation.

An associative analysis of object memory.

Different aspects of recognition memory in rodents are commonly assessed using variants of the spontaneous object recognition procedure in which animals explore objects that differ in terms of their novelty, recency, or where they have previously been presented. The present article describes three standard variants of this procedure, and outlines a theory of associative learning, SOP which can offer an explanation of performance on all three types of task. The implications of this for theoretical interpretations of recognition memory and the procedures used to explore it are discussed.

Effects of dorsal hippocampal damage on conditioning and conditioned-response timing: A pooled analysis.

Behavioral findings suggest that the dorsal hippocampus (DHPC) plays a role in timing of appetitive conditioned responding. The present article explored the relationship between the extent of DHPC damage and timing ability, in a pooled analysis of three published studies from our laboratory. Initial analyses of variance confirmed our previous reports that DHPC damage reduced peak time (a measure of timing accuracy). However, the spread (a measure of timing precision) was unchanged, such that the coefficient of variation (spread/peak time) was significantly larger in DHPC-lesioned animals. This implies that, in addition to the well-established effect of DHPC lesions on timing accuracy, DHPC damage produced a deficit in precision of timing. To complement this analysis, different generalized linear mixed-effects models (GLMMs) were performed on the combined dataset, to examine which combinations of the different behavioral measures of timing were the best predictors of the degree of hippocampal damage. The results from the GLMM analysis suggested that the greater the DHPC damage, the greater the absolute difference between the observed peak time and reinforced duration. Nevertheless, this systematic relationship between damage and performance was not specific to the temporal domain: paradoxically the greater the damage the greater the magnitude of peak responding. We discuss these lesion effects in terms of scalar timing theory.

Overshadowing by fixed- and variable-duration stimuli.

Two experiments investigated the effect of the temporal distribution form of a stimulus on its ability to produce an overshadowing effect. The overshadowing stimuli were either of the same duration on every trial, or of a variable duration drawn from an exponential distribution with the same mean duration as that of the fixed stimulus. Both experiments provided evidence that a variable-duration stimulus was less effective than a fixed-duration cue at overshadowing conditioning to a target conditioned stimulus (CS); moreover, this effect was independent of whether the overshadowed CS was fixed or variable. The findings presented here are consistent with the idea that the strength of the association between CS and unconditioned stimulus (US) is, in part, determined by the temporal distribution form of the CS. These results are discussed in terms of time-accumulation and trial-based theories of conditioning and timing.

Relative recency influences object-in-context memory.

In two experiments rats received training on an object-in-context (OIC) task, in which they received preexposure to object A in context x, followed by exposure to object B in context y. In a subsequent test both A and B are presented in either context x or context y. Usually more exploration is seen of the object that has not previously been paired with the test context, an effect attributed to the ability to remember where an object was encountered. However, in the typical version of this task, object A has also been encountered less recently than object B at test. This is precisely the arrangement in tests of 'relatively recency' (RR), in which more remotely presented objects are explored more than objects experienced more recently. RR could contaminate performance on the OIC task, by enhancing the OIC effect when animals are tested in context y, and masking it when the test is in context x. This possibility was examined in two experiments, and evidence for superior performance in context y was obtained. The implications of this for theoretical interpretations of recognition memory and the procedures used to explore it are discussed.

SSCC TD: a serial and simultaneous configural-cue compound stimuli representation for temporal difference learning.

This paper presents a novel representational framework for the Temporal Difference (TD) model of learning, which allows the computation of configural stimuli--cumulative compounds of stimuli that generate perceptual emergents known as configural cues. This Simultaneous and Serial Configural-cue Compound Stimuli Temporal Difference model (SSCC TD) can model both simultaneous and serial stimulus compounds, as well as compounds including the experimental context. This modification significantly broadens the range of phenomena which the TD paradigm can explain, and allows it to predict phenomena which traditional TD solutions cannot, particularly effects that depend on compound stimuli functioning as a whole, such as pattern learning and serial structural discriminations, and context-related effects.

Dissociations in the effect of delay on object recognition: evidence for an associative model of recognition memory.

Rats were administered 3 versions of an object recognition task: In the spontaneous object recognition task (SOR) animals discriminated between a familiar object and a novel object; in the temporal order task they discriminated between 2 familiar objects, 1 of which had been presented more recently than the other; and, in the object-in-place task, they discriminated among 4 previously presented objects, 2 of which were presented in the same locations as in preexposure and 2 in different but familiar locations. In each task animals were tested at 2 delays (5 min and 2 hr) between the sample and test phases in the SOR and object-in-place task, and between the 2 sample phases in the temporal order task. Performance in the SOR was poorer with the longer delay, whereas in the temporal order task performance improved with delay. There was no effect of delay on object-in-place performance. In addition the performance of animals with neurotoxic lesions of the dorsal hippocampus was selectively impaired in the object-in-place task at the longer delay. These findings are interpreted within the framework of Wagner's (1981) model of memory.