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Verapamil/Curcumin treatment attenuates the behavioral alterations observed in Williams Syndrome mice by regulation of MAPK pathway and Microglia overexpression

Williams-Beuren syndrome (WBS) is a rare neurodevelopmental disorder characterized by a distinctive cognitive phenotype for which there currently are not any effective treatments. We investigated the progression of behavioral deficits present in CD (complete deletion) mice, a rodent model of WBS, after chronic treatment with curcumin, verapamil and a combination of both. These compounds have been proven to have beneficial effects over different cognitive aspects of various murine models and thus, may have neuroprotective effects in WBS. Treatment was administered orally dissolved in drinking water. A set of behavioral tests demonstrated the efficiency of combinatorial treatment. Some histological and molecular analyses were performed to analyze the effects of treatment and its underlying mechanism in CD mice. Behavioral improvement correlates with the molecular recovery of several affected pathways regarding MAPK signaling, in tight relation with the control of synaptic transmission. Moreover, CD mice showed an increased activated microglia density in different brain regions, which was prevented by treatment. Therefore, results show that treatment prevented behavioral deficits by recovering altered gene expression in cortex of CD mice, reducing activated microglia and normalizing Bdnf expression levels. These findings unravel the mechanisms underlying the beneficial effects of this novel treatment on behavioral deficits observed in CD mice, and suggest that the combination of curcumin and verapamil could be a potential candidate to treat the cognitive impairments in WBS patients.

animal behavior and cognition↗

Amelioration of age-related cognitive decline and anxiety in mice by Centella asiatica extract varies by sex, dose and mode of administration.

We have previously reported that a water extract (CAW) of the Ayurvedic plant Centella asiatica administered in drinking water can improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here we compared the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice. Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.2, 0.5 or 1% w/w) to provide 0, 200 mg/kg/d, 500 mg/kg/d or 1000 mg/kg/d for a total of 5 weeks. An additional group of eighteen-month-old mice were treated with CAW (10 mg/mL) in their drinking water for a total of five weeks to deliver the same exposure of CAW as the highest dietary dose (1000 mg/kg/d). CAW doses delivered were calculated based on food and water consumption measured in previous experiments. In the fourth and fifth weeks, mice underwent behavioral testing of cognition, anxiety and depression (n=12 of each sex per treatment group in each test). Aged mice of both sexes showed cognitive deficits relative to young mice while only female aged mice showed increased anxiety compared to the young female mice and no differences in depression were observed between the different ages. CAW (1000 mg/kg/d) in the drinking water improved deficits in aged mice in learning, executive function and recognition memory in both sexes and attenuated the increased measures of anxiety observed in the aged female mice. However, CAW in the diet only improved executive function in aged mice at the highest dose (1000 mg/kg/d) in both sexes and did so less robustly than when given in the water. There were no effects of CAW on depression-like behavior in aged animals regardless of whether it was administered in the diet or the water. These results suggest that CAW can ameliorate age-related changes in measures of anxiety and cognition and that the mode of administration is important for the effects of CAW on resilience to these age-related changes.

animal behavior and cognition↗

Visual social information use in collective foraging

Collective dynamics emerge from individual-level decisions, yet we still poorly understand the link between individual-level decision-making processes and collective outcomes in realistic physical systems. Using collective foraging to study the key trade-off between personal and social information use, we present a mechanistic, spatially-explicit agent-based model that combines individual-level evidence accumulation of personal and (visual) social cues with particle-based movement. Under idealized conditions without physical constraints, our mechanistic framework reproduces findings from established probabilistic models, but explains how individual-level decision processes generate collective outcomes in a bottom-up way. In clustered environments, groups performed best if agents reacted strongly to social information, while in uniform environments, individualistic search was most beneficial. Incorporating different real-world physical and perceptual constraints profoundly shaped collective performance, and could even buffer maladaptive herding by facilitating self-organized exploration. Our study uncovers the mechanisms linking individual cognition to collective outcomes in human and animal foraging and paves the way for decentralized robotic applications. Significance statementFinding and collecting rewards in heterogeneous environments is key for adaptive collective behavior in humans, animals and machines. We present an open agent-based simulation framework to study how social information use shapes collective foraging from the bottom up. Our model combines individual evidence accumulation with spatially explicit movement. Our results connect individual-level decisions to collective dynamics in realistic physical environments, highlighting the key role of real-world constraints, thereby bringing us closer to embodied collective intelligence. Our work introduces a flexible platform to study the interplay between individual cognitive and perceptual biases, agents physical environment and the resulting collective dynamics and thus paves the way for fully decentralized mobile robot applications.

animal behavior and cognition↗

Honey bees solve a multi-comparison ranking task by probability matching

Honey bees forage on a range of flowers, all of which can vary unpredictably in the amount and type of rewards they offer. In this environment bees are challenged with maximising the resources they gather for their colony. That bees are effective foragers is clear, but how bees solve this type of complex multi-choice task is unknown. Here we challenged bees with a five-comparison choice task in which five colours differed in their probability of offering reward and punishment. The colours were ranked such that high ranked colours were more likely to offer reward, and the ranking was unambiguous. Bees choices in unrewarded tests matched their individual experiences of reward and punishment of each colour, indicating bees solved this test not by comparing or ranking colours but by matching their preferences to their history of reinforcement for each colour. We used a computational model to explore the feasibility of this probability matching strategy for the honey bee brain. The model suggested a structure like the honey bee mushroom body with reinforcement-related plasticity at both input and output was sufficient for this cognitive strategy. We discuss how probability matching enables effective choices to be made without a need to compare any stimuli directly, and the utility and limitations of this simple cognitive strategy for foraging animals.

animal behavior and cognition↗

Biological aging of two innate behaviors of Drosophila melanogaster: escape climbing versus courtship learning and memory

Motor and cognitive aging can severely affect life quality of elderly people and burden health care systems. In search for diagnostic behavioral biomarkers, it has been suggested that walking speed can predict forms of cognitive decline, but in humans, it remains challenging to separate the effects of biological aging and lifestyle. We examined a possible association of motor and cognitive decline in Drosophila, a genetic model organism of healthy aging. Long term courtship memory is present in young flies but absent already during mid life (4-8 weeks). By contrast, courtship learning index and short term memory (STM) are surprisingly robust and remain stable through mid (4-8 weeks) and healthy late life (>8 weeks), until courtship performance collapses suddenly at [~]4.5 days prior to death. By contrast, climbing speed declines gradually during late life (>8 weeks). The collapse of courtship performance and short term memory close to the end of life are not related to the gradual late life decline in climbing speed. Thus, during healthy aging in Drosophila, climbing and courtship motor behaviors decline differentially, unlikely share a common cause, and motor and cognitive performance decline are not closely associated to each other.

animal behavior and cognition↗

Ape cultures do not require behavior copying

While culture is widespread in the animal kingdom, human culture has been claimed to be special due to being cumulative. It is currently debated which cognitive abilities support cumulative culture, but behavioural form copying is one of the main abilities proposed. One important source of contention is the presence or absence of behaviour copying in our closest living relatives, non-human great apes (apes) – especially given that their behaviour does not show clear signs of cumulation. Those who claim that apes copy behaviour often base this claim on the existence of stable ape cultures in the wild. We developed an individual-based model to test whether ape cultural patterns can emerge in absence of any behaviour copying, when only allowing for a well-supported alternative social learning mechanism, socially mediated reinnovation, where only the frequency of reinnovation is under social influence, but the form of the behaviour is not. Our model reflects wild ape life conditions, including physiological and behavioural needs, demographic and spatial features, and possible genetic and ecological variation between populations. Our results show that, under a wide range of values of parameters, we can reproduce the defining features of wild ape cultural patterns. Overall, our results show that ape cultures can emerge and stabilise without behaviour copying. Ape cultures do not show the signatures of behaviour copying abilities, lending support to the notion that behaviour copying is, among apes, unique in the human lineage. It therefore remains an open question when and why behaviour copying evolved in hominins.Competing Interest StatementThe authors have declared no competing interest.View Full Text

animal behavior and cognition↗

Capturing Optimal and Suboptimal behavior Of Agents Via Structure Learning Of Their Internal Model

This study introduces a novel framework for understanding the cognitive underpinnings of individual behavior which often deviates from rational decision-making aimed at maximizing rewards in real-life scenarios. We propose a structure learning approach to infer an agents internal model, composed of a learning rule and an internal representation of the environment. Crucially, the combined contribution of these components -- rather than their individual contribution -- determines the overall optimality of the agents behavior. By exploring various combinations of learning rules and environment representations, we identify the most probable agent model structure for each individual. We apply this framework to analyze rats learning behavior in a free-choice task within a T-maze with return arms, evaluating different internal models based on optimal and suboptimal learning rules, along with multiple possible representations of the T-maze decision graph. Identifying the most likely agent model structure based on the rats behavioral data reveals that slower learning rats employed either a suboptimal or a moderately optimal agent model, whereas fast learners employ an optimal agent model. Using the inferred agent models for each rat, we explore the qualitative differences in their individual learning processes. Policy entropy, derived from the inferred agent models, also highlights variations in the balance between exploration and exploitation strategies among the rats. Traditional reinforcement learning approaches to addressing suboptimal behavior focus separately on either suboptimal learning rules or flawed environment representations. Our approach jointly models these components, revealing that suboptimal decisions can arise from complex interactions between learning rules and environment representations within an agents internal model. This provides deeper insights into the cognitive mechanisms underlying real-world decision-making.

animal behavior and cognition↗

On the generality and cognitive basis of base-rate neglect

Base rate neglect refers to peoples apparent tendency to underweight or even ignore base rate information when estimating posterior probabilities for events, such as the probability that a person with a positive cancer-test outcome actually does have cancer. While often replicated, almost all evidence for the phenomenon comes from studies that used problems with extremely low base rates, high hit rates, and low false alarm rates. It is currently unclear whether the effect generalizes to reasoning problems outside this "corner" of the entire problem space. Another limitation of previous studies is that they have focused on describing empirical patterns of the effect at the group level and not so much on the underlying strategies and individual differences. Here, we address these two limitations by testing participants on a broader problem space and modelling their responses at a single-participant level. We find that the empirical patterns that have served as evidence for base-rate neglect generalize to a larger problem space, albeit with large individual differences in the extent with which participants "neglect" base rates. In particular, we find a bi-modal distribution consisting of one group of participants who almost entirely ignore the base rate and another group who almost entirely account for it. This heterogeneity is reflected in the cognitive modeling results: participants in the former group were best captured by a linear-additive model, while participants in the latter group were best captured by a Bayesian model. We find little evidence for heuristic models. Altogether, these results suggest that the effect known as "base-rate neglect" generalizes to a large set of reasoning problems, but varies largely across participants and may need a reinterpretation in terms of the underlying cognitive mechanisms.

animal behavior and cognition↗

Collective dynamics support group drumming, reduce variability, and stabilize tempo drift

Humans are social animals who engage in a variety of collective activities requiring coordinated action. Among these, music is a defining and ancient aspect of human sociality. Human social interaction has largely been addressed in dyadic paradigms and it is yet to be determined whether the ensuing conclusions generalize to larger groups. Studied more extensively in nonhuman animal behaviour, the presence of multiple agents engaged in the same task space creates different constraints and possibilities than in simpler dyadic interactions. We addressed whether collective dynamics play a role in human circle drumming. The task was to synchronize in a group with an initial reference pattern and then maintain synchronization after it was muted. We varied the number of drummers, from solo to dyad, quartet, and octet. The observed lower variability, lack of speeding up, smoother individual dynamics, and leader-less inter-personal coordination indicated that stability increased as group size increased, a sort of temporal wisdom of crowds. We propose a hybrid continuous-discrete Kuramoto model for emergent group synchronization with pulse-based coupling that exhibits a mean field positive feedback loop. This research suggests that collective phenomena are among the factors that play a role in social cognition.

animal behavior and cognition↗

Chimpanzee play sequences are structured hierarchically as games

Social play is ubiquitous in the development of many animal species and involves players adapting actions flexibly to their own previous actions and partner responses. Play differs from other behavioural contexts for which fine-scale analyses of action sequences are available, such as tool use and communication, in that its form is not defined by its functions, making it potentially more unpredictable. In humans, play is often organised in games, where players know context-appropriate actions but string them together unpredictably. Here, we use the sequential nature of play elements to explore whether play elements in chimpanzees are structured hierarchically and follow predictable game-like patterns. Based on 5711 play elements from 143 bouts, we extracted individual-level play sequences of 11 Western chimpanzees (Pan troglodytes verus) of different ages from the Bossou community. We detected transition probabilities between play elements that exceeded expected levels and show that play elements form hierarchically clustered and interchangeable groups, indicative of at least six games that can be identified from transition networks, some with different roles for different players. We also show that increased information about preceding play elements improved predictability of subsequent elements, further indicating that play elements are not strung together randomly but that flexible action rules underlie their usage. Thus, chimpanzee play is hierarchically structured in short games which limit acceptable play elements and allow players to predict and adapt to partners actions. This grammar of action approach to social interactions can be valuable in understanding cognitive and communicative abilities within and across species.

animal behavior and cognition↗

Inter-species stimulus enhancement: Herring gulls (Larus argentatus) read human behaviour during foraging

Herring gulls are one of the few species that thrive in anthropogenic landscapes and their familiarity with people makes them an excellent target for studies of inter-species social cognition. Urban gulls pay attention to human behaviour in food-related contexts and we set out to investigate whether such cues can be used to redirect a gulls attention to potential food items in their environment. Herring gulls were given free choice of two differently coloured anthropogenic food items in the presence of a demonstrator, who was either sitting still or pretending to eat food from an item that matched one of the secondary food items. We found that a demonstrator mimicking eating significantly increased the likelihood of an approach or peck. Furthermore, 95% of pecks were directed towards the secondary food item which colour-matched the demonstrators food item. The results show situation-dependent attentional modulation in gulls, whereby gulls are able to use human cues for stimulus enhancement and foraging decisions. Given the relatively recent history of urbanisation in herring gulls, this cross-species social information transfer is likely to be a by-product of the cognitive flexibility inherent in kleptoparasitic species.

animal behavior and cognition↗

The Effect of Human Presence and Activity Type on Innovative Problem-Solving of Urban Eurasian Red Squirrels.

O_LIHumans impact wildlife positively and negatively, and increasing evidence shows that humans potentially play a major role in shaping cognition in wild animals. Recent evidence suggests, in particular, that the ability to innovate (an important cognitive ability for urban wildlife) can be affected by humans. However, the specific anthropogenic factors associated with shaping animal cognitive performance remain unclear. C_LIO_LIHere, across 15 urban areas in Oulu, Finland, we recorded 64 wild Eurasian red squirrels interactions with a novel puzzle box (innovative problem-solving) to obtain a highly preferred food, hazelnuts. C_LIO_LIWe then examined how different levels of human presence nearby, types of activity (walking, dog walking, cycling, and playground activities), and distance to the nearest footpaths influenced squirrels innovative problem-solving ability - measured as solving success at the population level and solving latency at the individual level. C_LIO_LIAt the population level, higher mean human presence nearby significantly decreased the proportion of squirrels that successfully solved the novel food-extraction problem ("innovators"), and greater human presence nearby decreased first-visit solving latency at individual level. Except for cycling, all types of human activities (walking, dog walking, and playground activity) significantly decreased first-visit success rate. Dog walking and playground activity had a greater negative impact on success rate at the population level than walking. Dog walking was the only outstanding factor affecting first-success latency. We also detected interaction effects between the types of human activities and nearest footpath on overall success rate of all innovators. C_LIO_LIThese results provide evidence for the negative effect of specific human-related factors on squirrels innovative problem-solving abilities. These factors may also exert selective pressure, potentially shaping the evolution of wildlife cognition. C_LI

animal behavior and cognition↗

Common marmosets (Callithrix jacchus) excel in a one-trial spatial memory test, yet perform poorly in a classical memory task

When quantifying animal cognition, memory represents one of the most tested domains and is key to understanding cognitive evolution. Memory tests thus play an important role in comparative cognitive research, yet slight variations in the experimental settings can substantially change the outcome, questioning whether different memory tests tap into different memory systems or whether they test memory at all. Here, we first assessed memory performance of 16 common marmosets (Callithrix jacchus) in two distinct paradigms varying in their format and delay. First, we examined marmoset memory in a 24-hour delay memory test (24h-DMT) in which they could freely explore an environment with three novel objects of which one contained food. We examined their retention the day after, and the procedure was iterated cumulatively with previous objects remaining in the enclosure until the marmosets had to choose the correct out of 30 objects. Second, we administered a classical delayed response test (DRT) in the same animals with three objects and a maximum delay of 30 seconds. In the DRT, marmoset performance was poor and not better than chance after 15 seconds already. However, individuals excelled in the 24h-DMT, performing above chance level after 24h even with tenfold the number of objects to choose from compared to the DRT. Moreover, individual performances in the two tests were not correlated, and typical age effects on memory could not be detected in both experiments. Together, these results suggest that the two tests explore different domains, and that the 24h-DMT examines long-term memory. The outcome of the DRT is more difficult to assign to memory since individuals performed only moderately even in the 0-second delay condition. This puts into question whether this task design indeed tests memory or other cognitive processes.

animal behavior and cognition↗

Apidae BeeHavioural response to shape-neutral visual stimuli in natural setup

Floral displays attract pollinators through a finely tuned interplay of colour, pattern, shape, and scent. Yet, the question remains: how do bees respond when these traits are stripped to their simplest form, with only visual cues at play? In this field study, we examined the foraging behaviour of Apis mellifera on artificial flowers differing solely in background colour (white or yellow) and UV patterning, while shape and scent were held constant. Across three summer days, standardized stimuli were placed within a natural meadow, and bee-flower interactions were recorded and analyzed by Bayesian hierarchical models. The results reveal a clear preference for yellow over white backgrounds and prolonged visitation in the presence of ring-shaped UV patterns, whereas full UV coverage acted as a deterrent. These effects, though moderate, were consistently modulated by abiotic covariates, particularly radiation, temperature, and time of day. Negligible inter-individual variation and a substantial share of residual variance further underline the context-dependent complexity of foraging. In sum, our findings demonstrate that visual floral traits, while influential, are interpreted through the dual lens of environmental contingency and the bees inherent cognitive machinery.

animal behavior and cognition↗

Repeated within-session rule switching in the marmoset: a paradigm for tracking the dynamics of cognitive flexibility

Adapting behaviour when reward contingencies change is a core function of cognitive control, but the underlying trial-by-trial computations are hard to observe when tasks cue each rule or allow only one switch per session. We developed the Feature-Rule Switching Task (FRST), in which common marmosets (Callithrix jacchus) repeatedly switch, without cues and under a fixed stimulus set, among the visual features that earn reward, inferring each switch from feedback alone. All four animals acquired the task within two days and sustained several switches per session across months of testing. A reinforcement-learning model with a learned weighting of stimulus dimensions best explained choices in every animal, outperforming complexity-matched perseveration controls. Learning-rate estimates fell within the human range, and in almost every session the animals weighted a stimulus dimension rather than individual features alone, with a dimensional commitment comparable in strength to that of humans. FRST thus provides a primate paradigm, amenable to laminar recording, for tracking the dynamics of cognitive flexibility.

animal behavior and cognition↗

Semantic map learning and externalization in an embodied neural agent: A comparison to human behavioral and neural data

All mammals can build internal cognitive maps from sensory input, supporting spatial learning and planning. While rodent studies have shown the mammalian navigation system solves the SLAM (Simultaneous Localization and Mapping) problem, its role in human spatial memory and overt recall are less understood. To investigate this, we adapted a spiking semantic SLAM algorithm for a "Treasure Hunt" task, where human participants navigate a 3D beach in virtual reality and later point to remembered object locations. Our agent integrates networks for bipedal locomotion, vision, memory, and arm control to enable first-person learning of place-object associations, and externalizing that knowledge by pointing and expressing confidence. Comparing model observables to human data, we replicate key behavioral and neural effects: monotonic scaling of accuracy with confidence, and recall-dependence on local field potential power observed in the left hippocampus. This work offers a mechanistic framework linking embodied navigation, memory, and communication in human spatial cognition.

animal behavior and cognition↗

Similarities and differences in spatial and non-spatial cognitive maps

Learning and generalization in spatial domains is often thought to rely on a "cognitive map", representing relationships between spatial locations. Recent research suggests that this same neural machinery is also recruited for reasoning about more abstract, conceptual forms of knowledge. Yet, to what extent do spatial and conceptual reasoning share common computational principles, and what are the implications for behavior? Using a within-subject design we studied how participants used spatial or conceptual distances to generalize and search for correlated rewards in successive multi-armed bandit tasks. Participant behavior indicated sensitivity to both spatial and conceptual distance, and was best captured using a Bayesian model of generalization that formalized distance-dependent generalization and uncertainty-guided exploration as a Gaussian Process regression with a radial basis function kernel. The same Gaussian Process model best captured human search decisions and judgments in both domains, and could simulate realistic learning curves, where we found equivalent levels of generalization in spatial and conceptual tasks. At the same time, we also find characteristic differences between domains. Relative to the spatial domain, participants showed reduced levels of uncertainty-directed exploration and increased levels of random exploration in the conceptual domain. Participants also displayed a one-directional transfer effect, where experience in the spatial task boosted performance in the conceptual task, but not vice versa. While confidence judgments indicated that participants were sensitive to the uncertainty of their knowledge in both tasks, they did not or could not leverage their estimates of uncertainty to guide exploration in the conceptual task. These results support the notion that value-guided learning and generalization recruit cognitive-map dependent computational mechanisms in spatial and conceptual domains. Yet both behavioral and model-based analyses suggest domain specific differences in how these representations map onto actions. Author summaryThere is a resurgence of interest in "cognitive maps" based on recent evidence that the hippocampal-entorhinal system encodes both spatial and non-spatial relational information, with far-reaching implications for human behavior. Yet little is known about the commonalities and differences in the computational principles underlying human learning and decision making in spatial and non-spatial domains. We use a within-subject design to examine how humans search for either spatially or conceptually correlated rewards. Using a Bayesian learning model, we find evidence for the same computational mechanisms of generalization across domains. While participants were sensitive to expected rewards and uncertainty in both tasks, how they leveraged this knowledge to guide exploration was different: participants displayed less uncertainty-directed and more random exploration in the conceptual domain. Moreover, experience with the spatial task improved conceptual performance, but not vice versa. These results provide important insights about the degree of overlap between spatial and conceptual cognition.

animal behavior and cognition↗

FloBuzz: A Modular Feeder System for Automated Aversive Conditioning in Bees

Understanding how environmental stressors affect pollinator behavior is essential for assessing ecosystem health. Automated flower and robotic feeder systems (AFRFSs) have transformed how pollinator foraging and learning are studied. Still, most systems remain reward-centric, limiting their ability to probe aversive learning and nociception under field conditions. Here, we present FloBuzz, a modular AFRFS that couples automated reward delivery with computer-vision-based visit detection to trigger closed-loop electric-shock stimulation in free-flying honey bees. In our setup, FloBuzz consisted of a 3D-printed feeder with a shock grid, a syringe pump with fluid-level feedback, and an electric shock stimulus trigger module that applied user-defined shock patterns. In a proof-of-concept trial that alternated between shock-free, 6 V, and shock-free, 9 V intervals, bee visitation increased over time during shock-free periods but declined during shock periods, with a steeper decline at 9 V than at 6 V, demonstrating a voltage-dependent avoidance. By enabling programmable, time-resolved aversive stimulation at an artificial flower in outdoor conditions, FloBuzz expanded AFRFS capabilities beyond purely reward-based paradigms. Evidently, FloBuzzs modular design will permit the investigation of diverse behavioral paradigms, including studies of toxin exposure, cognitive plasticity, and reward processing.

animal behavior and cognition↗