Behavioural abnormalities in a novel mouse model for Silver Russell Syndrome.

Silver Russell Syndrome (SRS) syndrome is an imprinting disorder involving low birth weight with complex genetics and diagnostics. Some rare SRS patients carry maternally inherited microduplications spanning the imprinted genes CDKN1C, PHLDA2, SLC22A18 and KCNQ1, suggesting that overexpression of one of more of these genes contributes to the SRS phenotype. While this molecular alteration is very rare, feeding difficulties are a very common feature of this condition. Given that SRS children also have very low body mass index, understanding the underpinning biology of the eating disorder is important, as well as potential co-occurring behavioural alterations. Here, we report that a mouse model of this microduplication exhibits a number of behavioural deficits. The mice had a blunted perception of the palatability of a given foodstuff. This perception may underpin the fussiness with food. We additionally report hypoactivity, unrelated to anxiety or motoric function, and a deficit in the appropriate integration of incoming sensory information. Importantly, using a second genetic model, we were able to attribute all altered behaviours to elevated expression of a single gene, Cdkn1c. This is the first report linking elevated Cdkn1c to altered behaviour in mice. Importantly, the findings from our study may have relevance for SRS and highlight a potentially underreported aspect of this disorder.

Reward Adaptation and the Mechanisms of Learning: Contrast Changes Reward Value in Rats and Drives Learning.

Formal theories of learning suggest that associations between events are determined by the internal representations of those events. Thus, learning should depend on perceived reward value-even when perceptions differ from objective values. We examined this prediction in flavor-preference learning in rats. In two experiments, simultaneous contrast either increased perceived reward value, which was paired with a distinctive flavor cue (the positive conditioned stimulus, CS+), or decreased the perceived value of the same reward, which was then paired with a second flavor (the negative conditioned stimulus, CS-). Even though the CS+ and CS- were paired with the same objective reward, there was a preference for the CS+ in subsequent tests. Moreover, the size of contrast-produced changes in reward value during training predicted the preference for the CS+ at test. This contrast-produced learning effect illustrates the mechanisms by which associations, which normally track veridical relationships between events in the world, are formed.

Nonreinforced flavor exposure attenuates the effects of conditioned taste aversion on both flavor consumption and cue palatability.

Nonreinforced exposure to a cue tends to attenuate subsequent conditioning with that cue-an effect referred to as latent inhibition (LI). In the two experiments reported here, we examined LI effects in the context of conditioned taste aversion by examining both the amount of consumption and the microstructure of the consummatory behavior (in terms of the mean size of lick clusters). The latter measure can be taken to reflect affective responses to, or the palatability of, the solution being consumed. In both experiments, exposure to a to-be-conditioned flavor prior to pairing the flavor with nausea produced by lithium chloride attenuated both the reduction in consumption and the reduction in lick cluster sizes typically produced by taste aversion learning. In addition, we observed a tendency (especially in the lick cluster measure) for nonreinforced exposure to reduce neophobic responses to the test flavors. Taken together, these results reinforce the suggestion from previous experiments using taste reactivity methods that LI attenuates the effects of taste aversion on both consumption and cue palatability. The present results also support the suggestion that the failure in previous studies to see concurrent LI effects on consumption and palatability was due to a context specificity produced by the oral taste infusion methods required for taste reactivity analyses. Finally, the fact that the pattern of extinction of conditioned changes in consumption and in lick cluster sizes was not affected by preexposure to the cue flavors suggests that LI influenced the quantity but not the quality of conditioned taste aversion.

Characterisation of the neural basis underlying appetitive extinction & renewal in Cacna1c rats.

Recent studies have revealed impairments in Cacna1c ± heterozygous animals (a gene that encodes the Cav 1.2 L-type voltage-gated calcium channels and is implicated in risk for multiple neuropsychiatric disorders) in aversive forms of learning, such as latent inhibition, reversal learning or context discrimination. However, the role of Cav 1.2 L-type voltage-gated calcium channels in extinction of appetitive associations remains under-investigated. Here, we used an appetitive Pavlovian conditioning task and evaluated extinction learning (EL) with a change of context from that of training and test (ABA) and without such a change (AAA) in Cacna1c ± male rats versus their wild-type (WT) littermates. In addition, we used fluorescence in situ hybridization of somatic immediate early genes (IEGs) Arc and Homer1a expression to scrutinize associated changes in the medial prefrontal cortex and the amygdala. Cacna1c ± animals successfully adapt their responses by engaging in appetitive EL and renewal. However, the regional IEG expression profile changed. For the EL occurring in the same context, Cacna1c ± animals presented higher IEG expression in the infralimbic cortex and the central amygdala than controls. The prelimbic region presented a larger neural ensemble in Cacna1c ± than WT animals, co-labelled for the time window of EL in the original context and prolonged exposure to the unrewarded context. With a context change, the Cacna1c ± infralimbic region displayed higher IEG expression during renewal than controls. Taken together, our findings provide novel evidence of distinct brain activation patterns occurring in Cacna1c ± rats after appetitive extinction and renewal despite preserved behavioral responses. This article is part of the Special Issue on "L-type calcium channel mechanisms in neuropsychiatric disorders".

Sinking In: The Peripheral Baldwinisation of Human Cognition.

The Baldwin effect is a hypothetical process in which a learned response to environmental change evolves a genetic basis. Modelling has shown that the Baldwin effect offers a plausible and elegant explanation for the emergence of complex behavioural traits, but there is little direct empirical evidence for its occurrence. We highlight experimental evidence of the Baldwin effect and argue that it acts preferentially on peripheral rather than on central cognitive processes. Careful scrutiny of research on taste-aversion and fear learning, language, and imitation indicates that their efficiency depends on adaptively specialised input and output processes: analogues of scanner and printer interfaces that feed information to core inference processes and structure their behavioural expression.

Licking microstructure and hedonic changes after flavour preference learning in rats.

Pairing a neutral flavour conditioned stimulus (CS) with a nutrient reward will create a learned preference for that CS. Prior studies suggest that this is accompanied by an increase in the hedonic value of the CS, although the reliability of this effect is yet to be fully established. Here, flavour CS+s were mixed with either 16% sucrose or maltodextrin (with control CS-s mixed with 2% solutions of the same carbohydrate). While a reliable preference for the CS+ was seen in every case, and there was a learned increase in lick cluster size when all conditions were considered together, this difference was significant in only one experimental condition considered alone. A meta-analysis of these results and similar published licking microstructure analysis studies found that the Cohen's dav effect size for changes in licking microstructure after flavour preference learning was 0.16. This is far smaller than the effect sizes reported when assessing learned hedonic changes in flavour preference based on other test or training methods. Although this confirms that flavour preference learning produces hedonic changes in the cue flavours, the analysis of licking microstructure with training based on voluntary consumption of CS and unconditioned stimulus (US) compounds may be an insensitive means of assessing such effects.

Reasoning versus association in animal cognition: Current controversies and possible ways forward.

The study of animal cognition is rife with controversy, and among the most long-standing and most intensely debated controversies in the field is the question of the extent to which the behavior of nonhuman animals can be fully understood on the basis of purely associative principles, or whether some behaviors exhibited by animals necessitate the assumption of inferential capacities in animals that defy an associative explanation. Remarkably, the continuing debate on the topic seems to be spawning little genuine progress in terms of substantial accumulation of new, generally accepted insights. As an introduction to a special section of the Journal of Comparative Psychology on the topic, the present article outlines a number of reasons for the stalemate and suggests ways to refertilize the debate. In particular, we claim that progress will not come from the adoption of general principles like Morgan's canon or the primacy of prediction over postdiction. Instead, emphasis should be placed on a careful analysis of what it is that different sides in the debate do and do not agree on and an increased willingness to engage in adversarial collaboration, in the spirit of a shared interest in furthering our understanding of animal behavior.

Functional brain networks underlying latent inhibition of conditioned disgust in rats.

The present experiment examined the neuronal networks involved in the latent inhibition of conditioned disgust by measuring brain oxidative metabolism. Rats were given nonreinforced intraoral (IO) exposure to saccharin (exposed groups) or water (non-exposed groups) followed by a conditioning trial in which the animals received an infusion of saccharin paired (or unpaired) with LiCl. On testing, taste reactivity responses displayed by the rats during the infusion of the saccharin were examined. Behavioral data showed that preexposure to saccharin attenuated the development of LiCl-induced conditioned disgust reactions, indicating that the effects of taste aversion on hedonic taste reactivity had been reduced. With respect to cumulative oxidative metabolic activity across the whole study period, the parabrachial nucleus was the only single region examined which showed differential activity between groups which received saccharin-LiCl pairings with and without prior non-reinforced saccharin exposure, suggesting a key role in the effects of latent inhibition of taste aversion learning. In addition, many functional connections between brain regions were revealed through correlational analysis of metabolic activity, in particular an accumbens-amygdala interaction that may be involved in both positive and negative hedonic responses.

Anhedonia in pigs? Effects of social stress and restraint stress on sucrose preference.

The fact that consumption of normally palatable foods is affected by stress in both humans and rats suggests a means to assess hedonic reaction in non-verbal animals. However, little is known about anhedonia and stress in productive animals such as pigs. Thus we examined the separate effects of social stress and restraint stress in 42-day old pigs on the preference for dilute sucrose solutions over water. Pigs in the social stress group (SS) were mixed with unfamiliar animals from separate pens for two 20 minute periods (Experiment 1). Pigs in the restraint stress group (RS) were immobilized three times a day, for 3-min periods, on 3 consecutive days (Experiment 2). Consumption of dilute sucrose solutions and water was examined after these stress manipulations and in the unstressed control groups (CG). Pigs were tested in pairs (12 control and 12 experimental) with a choice between water and sucrose solutions (at either 0.5% or 1%) during 30 min sessions. In both experiments CG pigs showed higher intakes of 0.5% and 1% sucrose solutions over water. Neither SS nor RS pigs consumed more 0.5% sucrose than water, but both groups did consume more 1% sucrose than water. Both social stress and restraint stress reduced sucrose preference at low concentrations but not at higher concentrations suggesting that stress may limit food consumption in pigs unless a palatable feed is present. In addition, the results suggest that stress reduces the hedonic impact of dilute sucrose. Therefore, sucrose preference may be a useful test for the presence of stress and anhedonia in pigs.