New Caledonian crows plan for specific future tool use.

The ability to plan for future events is one of the defining features of human intelligence. Whether non-human animals can plan for specific future situations remains contentious: despite a sustained research effort over the last two decades, there is still no consensus on this question. Here, we show that New Caledonian crows can use tools to plan for specific future events. Crows learned a temporal sequence where they were (a) shown a baited apparatus, (b) 5 min later given a choice of five objects and (c) 10 min later given access to the apparatus. At test, these crows were presented with one of two tool-apparatus combinations. For each combination, the crows chose the right tool for the right future task, while ignoring previously useful tools and a low-value food item. This study establishes that planning for specific future tool use can evolve via convergent evolution, given that corvids and humans shared a common ancestor over 300 million years ago, and offers a route to mapping the planning capacities of animals.

Fibroblast growth factor-mediated crosstalk in cancer etiology and treatment.

It is becoming increasingly evident that multiple cell types within the tumor work together to drive tumour progression and impact on both the response to therapy and the dissemination of tumour cells throughout the body. Fibroblast growth factor signalling (FGF) is perturbed in a number of tumors, serving to drive tumor cell proliferation and migration, but also has a central role in orchestrating the plethora of cells that comprise the tumor microenvironment. This review focuses on how this family of signalling molecules can influence the interactions between tumor cells and their surrounding environment. Unraveling the complexities of FGF signalling between the distinct cell types of a tumor may identify additional opportunities for FGF-targeted compounds in therapy and could help combat drug resistance. Developmental Dynamics 246:493-501, 2017. © 2017 Wiley Periodicals, Inc.

Western scrub-jays (Aphelocoma californica) solve multiple-string problems by the spatial relation of string and reward.

String-pulling is a widely used paradigm in animal cognition research to assess what animals understand about the functionality of strings as a means to obtain an out-of-reach reward. This study aimed to systematically investigate what rules Western scrub-jays (Aphelocoma californica) use to solve different patterned string tasks, i.e. tasks in which subjects have to choose between two or more strings of which only one is connected to the reward, or where one is more efficient. Arranging strings in a parallel configuration showed that the jays were generally capable of solving multiple-string tasks and acted in a goal-directed manner. The slanted and crossed configurations revealed a reliance on a "proximity rule", that is, a tendency to choose the string-end closest to the reward. When confronted with strings of different lengths attached to rewards at different distances the birds chose according to the reward distance, preferring the reward closest to them, and were sensitive to the movement of the reward, but did not consistently prefer the shorter and therefore more efficient string. Generally, the scrub-jays were successful in tasks where the reward was closest to the string-ends they needed to pull or when string length and reward distance correlated, but the birds had problems when the wrong string-end was closest to the reward or when the food items were in close proximity to each other. These results show that scrub-jays had a partial understanding of the physical principles underlying string-pulling but relied on simpler strategies such as the proximity rule to solve the tasks.

Effects of the mu-opioid receptor antagonist GSK1521498 on hedonic and consummatory eating behaviour: a proof of mechanism study in binge-eating obese subjects.

The opioid system is implicated in the hedonic and motivational processing of food, and in binge eating, a behaviour strongly linked to obesity. The aim of this study was to evaluate the effects of 4 weeks of treatment with the mu-opioid receptor antagonist GSK1521498 on eating behaviour in binge-eating obese subjects. Adults with body mass index ≥ 30 kg m(-2) and binge eating scale scores ≥ 19 received 1-week single-blind placebo run-in, and were then randomized to 28 days with either 2 mg day(-1) GSK1521498, 5 mg day(-1) GSK1521498 or placebo (N=21 per arm) in a double-blind parallel group design. The outcome measures were body weight, fat mass, hedonic and consummatory eating behaviour during inpatient food challenges, safety and pharmacokinetics. The primary analysis was the comparison of change scores in the higher-dose treatment group versus placebo using analysis of covariance at each relevant time point. GSK1521498 (2 mg and 5 mg) was not different from placebo in its effects on weight, fat mass and binge eating scores. However, compared with placebo, GSK1521498 5 mg day(-1) caused a significant reduction in hedonic responses to sweetened dairy products and reduced calorific intake, particularly of high-fat foods during ad libitum buffet meals, with some of these effects correlating with systemic exposure of GSK1521498. There were no significant effects of GSK1521498 2 mg day(-1) on eating behaviour, indicating dose dependency of pharmacodynamics. GSK1521498 was generally well tolerated and no previously unidentified safety signals were detected. The potential for these findings to translate into clinically significant effects in the context of binge eating and weight regain prevention requires further investigation.

Planning for the future by western scrub-jays.

Knowledge of and planning for the future is a complex skill that is considered by many to be uniquely human. We are not born with it; children develop a sense of the future at around the age of two and some planning ability by only the age of four to five. According to the Bischof-Köhler hypothesis, only humans can dissociate themselves from their current motivation and take action for future needs: other animals are incapable of anticipating future needs, and any future-oriented behaviours they exhibit are either fixed action patterns or cued by their current motivational state. The experiments described here test whether a member of the corvid family, the western scrub-jay (Aphelocoma californica), plans for the future. We show that the jays make provision for a future need, both by preferentially caching food in a place in which they have learned that they will be hungry the following morning and by differentially storing a particular food in a place in which that type of food will not be available the next morning. Previous studies have shown that, in accord with the Bischof-Köhler hypothesis, rats and pigeons may solve tasks by encoding the future but only over very short time scales. Although some primates and corvids take actions now that are based on their future consequences, these have not been shown to be selected with reference to future motivational states, or without extensive reinforcement of the anticipatory act. The results described here suggest that the jays can spontaneously plan for tomorrow without reference to their current motivational state, thereby challenging the idea that this is a uniquely human ability.

Cuttlefish retrieve whether they smelt or saw a previously encountered item.

According to the Source Monitoring Framework, the origin of a memory is remembered through the retrieval of specific features (e.g. perceptive, sensitive, affective signals). In two source discrimination tasks, we studied the ability of cuttlefish to remember the modality in which an item had been presented several hours ago. In Experiment 1, cuttlefish were able to retrieve the modality of presentation of a crab (visual vs olfactory) sensed before 1 h and 3 hrs delays. In Experiment 2, cuttlefish were trained to retrieve the modality of the presentation of fish, shrimp, and crabs. After training, cuttlefish performed the task with another item never encountered before (e.g. mussel). The cuttlefish successfully passed transfer tests with and without a delay of 3 hrs. This study is the first to show the ability to discriminate between two sensory modalities (i.e. see vs smell) in an animal. Taken together, these results suggest that cuttlefish can retrieve perceptual features of a previous event, namely whether they had seen or smelled an item.

Analysing hippocampal function in transgenic mice: an ethological perspective.

Advances in molecular genetics and technology have led to the dawn of a new era for neuroscience: manipulation of single genes now makes it possible to dissect the complexities of neurobiological phenotypes and to understand many of the intricacies of brain and behaviour, even in mammals. The phenotypical analysis of these mutant animals is complicated because the potential outcome of gene manipulation is difficult to predict. While behavioural analysis should form an integral part of any multidisciplinary research programme investigating the phenotypical effects of single genes on hippocampal function, it is crucial that the behavioural tests are designed and conducted appropriately. Approaches that take species-specific behavioural characteristics into account and use ethological methods could be the most useful for interpreting these behavioural findings and understanding the biological mechanisms of brain function.

The hippocampus and memory: a comparative and ethological perspective.

During the past year, considerable progress has been made in our understanding of the wide-ranging functions of the hippocampus. Highlights include the development of new tasks with which to assess spatial/topographic memory in humans and monkeys, novel tests of relational memory in rats, and episodic-like memory tasks in birds. In addition, novel theories of hippocampal function have been developed that are notable for their applicability to both humans and animal models.

Memory in food-storing birds: from behaviour to brain.

As a result of natural history studies, it has been hypothesized that food-storing birds may develop a special kind of memory to cope with the demand imposed by their food-storing behaviour (i.e. the ability to retrieve food from a wide variety of stores over varying amounts of time after storage). Recent studies on food-storing birds suggest that, at a relatively late stage in their development, the specific memories associated with food-storing behaviour can stimulate growth of the hippocampus, an area of the brain concerned with memory processing.

Memory and the hippocampus in food-storing birds: a comparative approach.

Comparative studies provide a unique source of evidence for the role of the hippocampus in learning and memory. Within birds and mammals, the hippocampal volume of scatter-hoarding species that cache food in many different locations is enlarged, relative to the remainder of the telencephalon, when compared with than that of species which cache food in one larder, or do not cache at all. Do food-storing species show enhanced memory function in association with the volumetric enlargement of the hippocampus? Comparative studies within the parids (titmice and chickadees) and corvids (jays, nutcrackers and magpies), two families of birds which show natural variation in food-storing behavior, suggest that there may be two kinds of memory specialization associated with scatter-hoarding. First, in terms of spatial memory, several scatter-hoarding species have a more accurate and enduring spatial memory, and a preference to rely more heavily upon spatial cues, than that of closely related species which store less food, or none at all. Second, some scatter-hoarding parids and corvids are also more resistant to memory interference. While the most critical component about a cache site may be its spatial location, there is mounting evidence that food-storing birds remember additional information about the contents and status of cache sites. What is the underlying neural mechanism by which the hippocampus learns and remembers cache sites? The current mammalian dogma is that the neural mechanisms of learning and memory are achieved primarily by variations in synaptic number and efficacy. Recent work on the concomitant development of food-storing, memory and the avian hippocampus illustrates that the avian hippocampus may swell or shrivel by as much as 30% in response to presence or absence of food-storing experience. Memory for food caches triggers a dramatic increase in the total number of number of neurons within the avian hippocampus by altering the rate at which these cells are born and die.

Effects of demanding foraging conditions on cache retrival accuracy in food-caching mountain chickadees (Poecile gambeli).

Birds rely, at least in part, on spatial memory for recovering previously hidden caches but accurate cache recovery may be more critical for birds that forage in harsh conditions where the food supply is limited and unpredictable. Failure to find caches in these conditions may potentially result in death from starvation. In order to test this hypothesis we compared the cache recovery behaviour of 24 wild-caught mountain chickadees (Poecile gambeli), half of which were maintained on a limited and unpredictable food supply while the rest were maintained on an ad libitum food supply for 60 days. We then tested their cache retrieval accuracy by allowing birds from both groups to cache seeds in the experimental room and recover them 5 hours later. Our results showed that birds maintained on a limited and unpredictable food supply made significantly fewer visits to non-cache sites when recovering their caches compared to birds maintained on ad libitum food. We found the same difference in performance in two versions of a one-trial associative learning task in which the birds had to rely on memory to find previously encountered hidden food. In a non-spatial memory version of the task, in which the baited feeder was clearly marked, there were no significant differences between the two groups. We therefore concluded that the two groups differed in their efficiency at cache retrieval. We suggest that this difference is more likely to be attributable to a difference in memory (encoding or recall) than to a difference in their motivation to search for hidden food, although the possibility of some motivational differences still exists. Overall, our results suggest that demanding foraging conditions favour more accurate cache retrieval in food-caching birds.

Hippocampal growth and maintenance depend on food-caching experience in juvenile mountain chickadees (Poecile gambeli).

This experiment investigated the development of caching behavior and the hippocampus (HF) in postfledging mountain chickadees (Poecile gambeli). From Days 35 to 53, the number of seeds stored increased but the proportion recovered did not. Birds that stored and recovered during 3 or more trials had significantly enlarged HF but not telencephalon volumes (experienced) compared with those that stored but did not recover (store only) and those deprived of caching experience altogether (deprived). HF size did not increase linearly with the number of experience trials. Birds that received less than 3 experience trials did not differ from deprived birds in HF size, suggesting a threshold effect. Experienced birds prevented from caching for 1 month had significantly smaller HF volumes than those examined immediately after caching experience and did not differ from deprived birds. Experience of both storing and recovery is required to initiate growth and maintain HF size.

Sexual dimorphism and species differences in HVC volumes of cowbirds.

Cowbirds exhibit extensive variation in their social, territorial, and reproductive behaviors. Nissl-stained brain sections of specimens from a previous study (J. C. Reboreda, N. S. Clayton, & A. Kacelnik, 1996) were used to study the gross anatomy of a song control nucleus in 3 South American cowbirds (bay-winged, Molothrus badius; shiny, M. bonariensis; and screaming, M. rufoaxillaris). Cowbird high vocal center (HVC) volumes were consistently higher in males than in females in all 3 species. The largest HVC size of females found in bay-winged cowbirds is consistent with observations that females of this species, but not of the other 2 species, occasionally sing. The extent of the sexual dimorphism of relative HVC size was highest for the sexually dichromatic and promiscuous shiny cowbirds and smaller for the monochromatic and monogamous bay-winged and screaming cowbirds, suggesting that selection pressures associated with morphological traits and social systems are reflected in brain architecture.

Species and sex differences in hippocampus size in parasitic and non-parasitic cowbirds.

To test the hypothesis that selection for spatial abilities which require birds to locate and to return accurately to host nests has produced an enlarged hippocampus in brood parasites, three species of cowbird were compared. In shiny cowbirds, females search for host nests without the assistance of the male; in screaming cowbirds, males and females inspect hosts' nests together; in bay-winged cowbirds, neither sex searches because this species is not a brood parasite. As predicted, the two parasitic species had a relatively larger hippocampus than the non-parasitic species. There were no sex differences in relative hippocampus size in screaming or bay-winged cowbirds, but female shiny cowbirds had a larger hippocampus than the male.

Effects of photoperiod on food-storing and the hippocampus in birds.

Birds that store food have a relatively large hippocampus compared to non-storing species. The hippocampus shows seasonal differences in neurogenesis and volume in black-capped chikadees (Parus atricapillus) taken from the wild at different times of year. We compared hippocampal volumes in black-capped chickadees captured at the same time but differing in food-storing behaviour because of manipulations of photoperiod in the laboratory. Differences in food-storing behaviour were not accompanied by differences in the volume of the hippocampus. Hippocampal volumes also did not differ between two groups of a non-food-storing control species, house sparrows (Passer domesticus), exposed to the same conditions as the chickadees.

Hippocampal volume does not change seasonally in a non food-storing songbird.

Seasonal differences in hippocampal morphology have been reported in food-storing birds. Non food-storing species have not been investigated however. It is therefore unclear whether seasonal changes in the hippocampus are specifically related to food-storing or reflect a more general seasonal mechanism that occurs in both food-storing and non food-storing birds alike. We determined the volumes of the hippocampal formation and remaining telencephalon in the non-storing male song sparrow (Melospiza melodies morphna) in two experiments comparing birds collected in the spring and fall of 1992-94 (Experiment 1) and 1997 (Experiment 2). Although pronounced seasonal changes in song control nuclei such as the HVC and RA were previously reported for the same brains used in Experiment 1, we found that hippocampal volume did not change with season in either Experiment 1 or 2 for these song sparrow brains. These results suggest that seasonal changes in the hippocampus do not occur in this non food-storing species and may be specific to food-storing birds.

The neuroethological development of food-storing memory: a case of use it, or lose it!

Some species of birds that scatter-hoard food e.g. marsh tits, Parus palustris, use memory to retrieve stored food. These scatter-hoarding species have a larger hippocampus relative to the rest of the telencephalon than do species that store little or no food e.g. blue tits, P. caeruleus. The difference in relative hippocampal volume arises after the young have fledged from the nest and recent work on the dual ontogeny of the hippocampus and memory in hand-raised marsh tits suggests that some aspect of memory for retrieving food (whether or not stored by the bird) can stimulate hippocampal growth in juveniles at a relatively late stage in their development.

Development of food-storing and the hippocampus in juvenile marsh tits (Parus palustris).

Food-storing birds, e.g., marsh tits, Parus palustris, use memory to retrieve stored food and have a larger hippocampus relative to the rest of the telencephalon than do species that store little or no food, e.g., blue tits, P. caeruleus. The difference in relative hippocampal volume arises after the young have fledged from the nest and recent work on the dual ontogeny of the hippocampus and memory in hand-raised marsh tits suggests that the hippocampal growth depends upon some aspect of the experience of storing and retrieving food. The aim of this experiment was to test whether hippocampal growth precedes or accompanies changes in food-storing behaviour. Hand-raised marsh tits were provided with the opportunity to store and retrieve food every third day from day 35 post-hatch and the volume of the hippocampus and remainder of the telencephalon was measured and compared with those of age-matched controls at three different stages (days 41, 47 and 56 post-hatch). Experience had no significant effect on telencephalon volume but experienced birds had larger absolute and relative hippocampal volumes than did controls at all stages of the experiment, even before the increase in food-storing intensity on day 44. The stage at which the birds were killed had a significant effect on the absolute volume of both the hippocampus and telencephalon but there was no significant interaction between experience and stage. The results suggest that both hippocampus and telencephalon continue to increase in volume between days 35 and 56 but that the hippocampus shows a additional increase in volume relative to telencephalon in the experienced groups. One interpretation of these results is that the one or two seeds stored before day 44 may have been sufficient to stimulate the growth of the hippocampus and that there is an increase in relative hippocampal volume in preparation for the increased memory demands associated with the sharp increase in food-storing.

Development of hippocampal specialisation in two species of tit (Parus spp.).

Food storing birds have been shown to have a larger hippocampus, relative to the rest of the telencephalon, than do non-storers. A previous study reported that this difference in relative hippocampal volume is not apparent in a comparison of nestling birds, but emerges after birds have fledged. This conclusion was based on a comparison of a storing and a non-storing species in the corvid family. The present study compared another storer/non-storer pair of species in order to test whether the results of the previous study can be replicated in another family of birds. The volumes of the hippocampal region and remainder of the telencephalon were measured and estimates of neuron size, density and total number in the hippocampal region were made for nestlings and adults of the food-storing marsh tit Parus palustris and non-storing blue tit Parus caeruleus. Relative hippocampal volume did not differ between nestlings of the two species, whilst the relative hippocampal volume of adult marsh tits was greater than that of blue tits. The difference between adults arose because in marsh tits but not blue tits, adults had a significantly larger relative hippocampal volume than did nestlings. Neuron density was significantly higher in both species in nestlings than in adults and adult blue tits had fewer neurons than did adult marsh tits. The results of this study are largely consistent with the earlier study comparing a storing and non-storing species of corvid, suggesting that the observed patterns may reflect a general difference between storers and non-storers in the development of the hippocampal region.