Postnatal Enrichment Corrects Deficits in Perineuronal Net Formation and Reversal Learning in Adult Mice Exposed to Early Adversity.

Childhood neglect is associated with cortical thinning, hyperactivity, and deficits in cognitive flexibility that are difficult to reverse later in life. Despite being the most prevalent form of early adversity, little is currently understood about the mechanisms responsible for these neurodevelopmental abnormalities, and no animal models have yet replicated key structural and behavioral features of childhood neglect/deprivation. To address these gaps, we have recently demonstrated that mice exposed to impoverished conditions, specifically limited bedding (LB), exhibit behavioral and structural changes that resemble those observed in adolescents who have experienced severe neglect. Here, we show that LB leads to long-term deficits in reversal learning, which can be fully reversed by briefly exposing LB pups to enrichment (toys) in their home cage from postnatal days 14 to 25. Reversal learning failed to induce normal c-fos activation in the orbitofrontal cortex (OFC) of LB mice, a deficit that was normalized by early enrichment. Additionally, LB decreased the density of parvalbumin-positive cells surrounded by perineuronal nets (PV+PNN+) and increased the ratio of glutamatergic to inhibitory synapse densities in the OFC, deficits that were also reversed by enrichment. Degradation of PNN in the OFC of adult mice impaired reversal learning, reduced c-fos activation, and increased the ratio of glutamatergic to inhibitory synapse densities in the OFC to levels comparable to those observed in LB mice. Collectively, our findings suggest that postnatal deprivation and enrichment impact the formation of PV+PNN+ cells in the OFC, a developmental process that is essential for cognitive flexibility in adulthood.

Exploring breed differences in discrimination, reversal learning, and resistance to extinction in the domestic dog (Canis familiaris).

Learning is crucial for shaping domestic dogs' behaviour through life experiences, yet not all breeds exhibit the same learning aptitude towards a particular task. The current study's objective was to identify differences in behaviour and learning performance across and within five breed clades and elucidate the underlying factors contributing into these variations. Dogs (n = 111) from five breed clades (UK Rural, Retrievers, Asian Spitz, European Mastiff, and New World) participated in a virtual learning task with their owners. Owners completed validated questionnaires of Impulsivity and Reward Responsiveness. The learning task comprised of reinforcing an arbitrary behaviour (hand-touch) through multiple sessions of Acquisition (reinforcing the hand-touch), Discrimination (reinforcing the hand-touch on one of two hands) and Reversal Learning (reinforcing the hand-touch on the opposite hand), followed by a single session of Extinction (hand-touch not reinforced). Results showed notable differences across the studied breed clades in certain learning and behavioural components. However, the observed disparities may not be entirely attributed to inherent cognitive differences among the breed clades but rather potentially influenced by contextual factors such as the human-dog communication dynamics associated with breeds' cooperativity. Furthermore, breed clades differed in the contributing factors predicting individual learning performances, which could highlight the potential effect of breeds' historical function.

Sex-dependent differences in the ability of nicotine to modulate discrimination learning and cognitive flexibility in mice.

Nicotine, an addictive compound found in tobacco, functions as an agonist of nicotinic acetylcholine receptors (nAChRs) in the brain. Interestingly, nicotine has been reported to act as a cognitive enhancer in both human subjects and experimental animals. However, its effects in animal studies have not always been consistent, and sex differences have been identified in the effects of nicotine on several behaviors. Specifically, the role that sex plays in modulating the effects of nicotine on discrimination learning and cognitive flexibility in rodents is still unclear. Here, we evaluated sex-dependent differences in the effect of daily nicotine intraperitoneal (i.p.) administration at various doses (0.125, 0.25, and 0.5 mg/kg) on visual discrimination (VD) learning and reversal (VDR) learning in mice. In male mice, 0.5 mg/kg nicotine significantly improved performance in the VDR, but not the VD, task, while 0.5 mg/kg nicotine significantly worsened performance in the VD, but not VDR task in female mice. Furthermore, 0.25 mg/kg nicotine significantly worsened performance in the VD and VDR task only in female mice. Next, to investigate the cellular mechanisms that underlie the sex difference in the effects of nicotine on cognition, transcriptomic analyses were performed focusing on the medial prefrontal cortex tissue samples from male and female mice that had received continuous administration of nicotine for 3 or 18 days. As a result of pathway enrichment analysis and protein-protein interaction analysis using gene sets of differentially expressed genes, decreased expression of postsynaptic-related genes in males and increased expression of innate immunity-related genes in females were identified as possible molecular mechanisms related to sex differences in the effects of nicotine on cognition in discrimination learning and cognitive flexibility. Our result suggests that nicotine modulates cognitive function in a sex-dependent manner by alternating the expression of specific gene sets in the medial prefrontal cortex.

Individuals with anxiety and depression use atypical decision strategies in an uncertain world.

Previous studies on reinforcement learning have identified three prominent phenomena: (1) individuals with anxiety or depression exhibit a reduced learning rate compared to healthy subjects; (2) learning rates may increase or decrease in environments with rapidly changing (i.e. volatile) or stable feedback conditions, a phenomenon termed learning rate adaptation; and (3) reduced learning rate adaptation is associated with several psychiatric disorders. In other words, multiple learning rate parameters are needed to account for behavioral differences across participant populations and volatility contexts in this flexible learning rate (FLR) model. Here, we propose an alternative explanation, suggesting that behavioral variation across participant populations and volatile contexts arises from the use of mixed decision strategies. To test this hypothesis, we constructed a mixture-of-strategies (MOS) model and used it to analyze the behaviors of 54 healthy controls and 32 patients with anxiety and depression in volatile reversal learning tasks. Compared to the FLR model, the MOS model can reproduce the three classic phenomena by using a single set of strategy preference parameters without introducing any learning rate differences. In addition, the MOS model can successfully account for several novel behavioral patterns that cannot be explained by the FLR model. Preferences for different strategies also predict individual variations in symptom severity. These findings underscore the importance of considering mixed strategy use in human learning and decision-making and suggest atypical strategy preference as a potential mechanism for learning deficits in psychiatric disorders.

Serial visual reversal learning in captive black-handed spider monkeys, Ateles geoffroyi.

Recent research suggests that socio-ecological factors such as dietary specialization and social complexity may be drivers of advanced cognitive skills among primates. Therefore, we assessed the ability of 12 black-handed spider monkeys (Ateles geoffroyi), a highly frugivorous platyrrhine primate with strong fission-fusion dynamics, to succeed in a serial visual reversal learning task. Using a two-alternative choice paradigm we first trained the animals to reliably choose a rewarded visual stimulus over a non-rewarded one. Upon reaching a pre-set learning criterion we then switched the reward values of the two stimuli and assessed if and how quickly the animals learned to reverse their choices, again to a pre-set learning criterion. This stimulus reversal procedure was then continued for a total of 80 sessions of 10 trials each. We found that the spider monkeys quickly learned to reliably discriminate between two simultaneously presented visual stimuli, that they succeeded in a visual reversal learning task, and that they displayed an increase in learning speed across consecutive reversals, suggesting that they are capable of serial reversal learning-set formation with visual cues. The fastest-learning individual completed five reversals within the 80 sessions. The spider monkeys outperformed most other primate and nonprimate mammal species tested so far on this type of cognitive task, including chimpanzees, with regard to their learning speed in both the initial learning task and in the first reversal task, suggesting a high degree of behavioral flexibility and inhibitory control. Our findings support the notion that socio-ecological factors such as dietary specialization and social complexity foster advanced cognitive skills in primates.

Poly (I:C)-induced maternal immune activation generates impairment of reversal learning performance in offspring.

Maternal immune activation (MIA) induces a variety of behavioral and brain abnormalities in offspring of rodent models, compatible with neurodevelopmental disorders, such as schizophrenia or autism. However, it remains controversial whether MIA impairs reversal learning, a basic expression of cognitive flexibility that seems to be altered in schizophrenia. In the present study, MIA was induced by administration of a single dose of polyriboinosinic-polyribocytidylic acid (Poly (I:C) (5 mg/kg i.p.)) or saline to mouse pregnant dams in gestational day (GD) 9.5. Immune activation was monitored through changes in weight and temperature. The offspring were evaluated when they reached adulthood (8 weeks) using a touchscreen-based system to investigate the effects of Poly (I:C) on discrimination and reversal learning performance. After an initial pre-training, mice were trained to discriminate between two different stimuli, of which only one was rewarded (acquisition phase). When the correct response reached above 80% values for two consecutive days, the images were reversed (reversal phase) to assess the adaptation capacity to a changing environment. Maternal Poly (I:C) treatment did not interfere with the learning process but induced deficits in reversal learning compared to control saline animals. Thus, the accuracy in the reversal phase was lower, and Poly (I:C) animals required more sessions to complete it, suggesting impairments in cognitive flexibility. This study advances the knowledge of how MIA affects behavior, especially cognitive domains that are impaired in schizophrenia. The findings support the validity of the Poly (I:C)-based MIA model as a tool to develop pharmacological treatments targeting cognitive deficits associated with neurodevelopmental disorders.

The Aggregation of α-Synuclein in the Dorsomedial Striatum Significantly Impairs Cognitive Flexibility in Parkinson's Disease Mice.

This study focused on α-synuclein (α-syn) aggregation in the dorsomedial striatum (DMS) so as to investigate its role in the cognitive flexibility of Parkinson's disease (PD). Here, we investigated the cognitive flexibility by assessing reversal learning abilities in MPTP-induced subacute PD model mice and in C57BL/6J mice with α-syn aggregation in the DMS induced by adenovirus (AAV-SNCA) injection, followed by an analysis of the target protein's expression and distribution. PD mice exhibited impairments in reversal learning, positively correlated with the expression of phosphorylated α-syn in the DMS. Furthermore, the mice in the AAV-SNCA group exhibited reversal learning deficits and a reduction in acetylcholine levels, accompanied by protein alterations within the DMS. Notably, the administration of a muscarinic receptor 1 (M1R) agonist was able to alleviate the aforementioned phenomenon. These findings suggest that the impaired cognitive flexibility in PD may be attributed to the diminished activation of acetylcholine to M1R caused by α-syn aggregation.

A social learning primacy trend in mate-copying: an experiment in Drosophila melanogaster.

Social learning is learning from the observation of how others interact with the environment. However, in nature, individuals often need to process serial social information and may favour either the most recent information (recency bias), constantly updating knowledge to match the environment, or the information that appeared first in the series (primacy bias), which may slow down adjustment to environmental change. Mate-copying is a widespread form of social learning in a mate choice context related to conformity in mate choice, and where a naive individual develops a preference for a given mate (or mate phenotype) seen being chosen by conspecifics. Mate-copying is documented in most vertebrate taxa and in the fruit fly Drosophila melanogaster. Here, we tested experimentally whether female fruit flies show a primacy or a recency bias by presenting pictures of a female copulating with one of two contrastingly coloured male phenotypes. We found that after two sequential contradictory demonstrations, females show a tendency to prefer males of the phenotype preferred in the first demonstration, suggesting that mate-copying in D. melanogaster is not based on the most recently observed mating and may be influenced by a form of primacy bias.

Experimental playback of urban noise does not affect cognitive performance in captive Australian magpies.

Exposure of wildlife to anthropogenic noise is associated with disruptive effects. Research on this topic has focused on behavioural and physiological responses of animals to noise, with little work investigating links to cognitive function. Neurological processes that maintain cognitive performance can be impacted by stress and sleep disturbances. While sleep loss impairs cognitive performance in Australian magpies, it is unclear whether urban noise, which disrupts sleep, can impact cognition as well. To fill this gap, we explored how environmentally relevant urban noise affected the performance of wild-caught, city-living Australian magpies (Gymnorhina tibicen tyrannica) on a cognitive task battery including associative and reversal learning, inhibitory control, and spatial memory. Birds were housed and tested in a laboratory environment; sample sizes varied across tasks (n=7-9 birds). Tests were conducted over 4 weeks, during which all magpies were exposed to both an urban noise playback and a quiet control. Birds were presented with the entire test battery twice: following exposure to, and in the absence of, an anthropogenic noise playback; however, tests were always performed without noise (playback muted during testing). Magpies performed similarly in both treatments on all four tasks. We also found that prior experience with the associative learning task had a strong effect on performance, with birds performing better on their second round of trials. Like previous findings on Australian magpies tested on the same tasks in the wild under noisy conditions, we could not find any disruptive effects on cognitive performance in a controlled experimental laboratory setting.

Fecal microbiota transplantation of patients with anorexia nervosa did not alter flexible behavior in rats.

OBJECTIVE: Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression. METHODS: In a preclinical study, we explored whether AN-derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase-cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety-like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests. RESULTS: Neither antibiotic-induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose-stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients. DISCUSSION: No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic-induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies. PUBLIC SIGNIFICANCE: While our study did not reveal direct impacts of AN-associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic-induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa.

Adolescent-to-adult gains in cognitive flexibility are adaptively supported by reward sensitivity, exploration, and neural variability.

Cognitive flexibility exhibits dynamic changes throughout development, with different forms of flexibility showing dissociable developmental trajectories. In this review, we propose that an adolescent-specific mode of flexibility in the face of changing environmental contingencies supports the emergence of adolescent-to-adult gains in cognitive shifting efficiency. We first describe how cognitive shifting abilities monotonically improve from childhood to adulthood, accompanied by increases in brain state flexibility, neural variability, and excitatory/inhibitory balance. We next summarize evidence supporting the existence of a dopamine-driven, adolescent peak in flexible behavior that results in reward seeking, undirected exploration, and environmental sampling. We propose a neurodevelopmental framework that relates these adolescent behaviors to the refinement of neural phenotypes relevant to mature cognitive flexibility, and thus highlight the importance of the adolescent period in fostering healthy neurocognitive trajectories.

Lesions to the mediodorsal thalamus, but not orbitofrontal cortex, enhance volatility beliefs linked to paranoia.

Beliefs-attitudes toward some state of the environment-guide action selection and should be robust to variability but sensitive to meaningful change. Beliefs about volatility (expectation of change) are associated with paranoia in humans, but the brain regions responsible for volatility beliefs remain unknown. The orbitofrontal cortex (OFC) is central to adaptive behavior, whereas the magnocellular mediodorsal thalamus (MDmc) is essential for arbitrating between perceptions and action policies. We assessed belief updating in a three-choice probabilistic reversal learning task following excitotoxic lesions of the MDmc (n = 3) or OFC (n = 3) and compared performance with that of unoperated monkeys (n = 14). Computational analyses indicated a double dissociation: MDmc, but not OFC, lesions were associated with erratic switching behavior and heightened volatility belief (as in paranoia in humans), whereas OFC, but not MDmc, lesions were associated with increased lose-stay behavior and reward learning rates. Given the consilience across species and models, these results have implications for understanding paranoia.

In relentless pursuit of the white whale: A role for the ventral midline thalamus in behavioral flexibility and adaption?

The reuniens (Re) nucleus is located in the ventral midline thalamus. It has fostered increasing interest, not only for its participation in a variety of cognitive functions (e.g., spatial working memory, systemic consolidation, reconsolidation, extinction of fear or generalization), but also for its neuroanatomical positioning as a bidirectional relay between the prefrontal cortex (PFC) and the hippocampus (HIP). In this review we compile and discuss recent studies having tackled a possible implication of the Re nucleus in behavioral flexibility, a major PFC-dependent executive function controlling goal-directed behaviors. Experiments considered explored a possible role for the Re nucleus in perseveration, reversal learning, fear extinction, and set-shifting. They point to a contribution of this nucleus to behavioral flexibility, mainly by its connections with the PFC, but possibly also by those with the hippocampus, and even with the amygdala, at least for fear-related behavior. As such, the Re nucleus could be a crucial crossroad supporting a PFC-orchestrated ability to cope with new, potentially unpredictable environmental contingencies, and thus behavioral flexibility and adaption.

Chemogenetic inactivation of the nucleus reuniens and its projections to the orbital cortex produce deficits on discrete measures of behavioral flexibility in the attentional set-shifting task.

The nucleus reuniens (RE) of the ventral midline thalamus is a critical node in the communication between the orbitomedial prefrontal cortex (OFC) and the hippocampus (HF). While RE has been shown to directly participate in memory-associated functions through its connections with the medial prefrontal cortex and HF, less is known regarding the role of RE in executive functioning. Here, we examined the involvement of RE and its projections to the orbital cortex (ORB) in attention and behavioral flexibility in male rats using the attentional set shifting task (AST). Rats expressing the hM4Di DREADD receptor in RE were implanted with indwelling cannulas in either RE or the ventromedial ORB to pharmacologically inhibit RE or its projections to the ORB with intracranial infusions of clozapine-N-oxide hydrochloride (CNO). Chemogenetic-induced suppression of RE resulted in impairments in reversal learning and set-shifting. This supports a vital role for RE in behavioral flexibility - or the ability to adapt behavior to changing reward or rule contingencies. Interestingly, CNO suppression of RE projections to the ventromedial ORB produced impairments in rule abstraction - or dissociable effects elicited with direct RE suppression. In summary, the present findings indicate that RE, mediated in part by actions on the ORB, serves a critical role in the flexible use of rules to drive goal directed behavior. The cognitive deficits of various neurological disorders with impaired communication between the HF and OFC, may be partly attributed to alterations of RE -- as an established intermediary between these cortical structures.

Going back to "basics": Harlow's learning set task with wolves and dogs.

To survive and reproduce, animals need to behave adaptively by adjusting their behavior to their environment, with learning facilitating some of these processes. Dogs have become a go-to model species in comparative cognition studies, making our understanding of their learning skills paramount at multiple levels, not only with regards to basic research on their cognitive skills and the effects of domestication, but also with applied purposes such as training. In order to tackle these issues, we tested similarly raised wolves and dogs in a serial learning task inspired by Harlow's "learning set." In Phase 1, different pairs of objects were presented to the animals, one of which was baited while the other was not. Both species' performance gradually improved with each new set of objects, showing that they "learnt to learn," but no differences were found between the species in their learning speed. In Phase 2, once subjects had learned the association between one of the objects and the food reward, the contingencies were reversed and the previously unrewarded object of the same pair was now rewarded. Dogs' performance in this task seemed to be better than wolves', albeit only when considering just the first session of each reversal, suggesting that the dogs might be more flexible than wolves. Further research (possibly with the aid of refined methods such as computer-based tasks) would help ascertain whether these differences between wolves and dogs are persistent across different learning tasks.

Behavioral Analysis of NMDAR Function in Rodents: Tests of Long-Term Spatial Memory.

NMDAR-dependent forms of synaptic plasticity in brain regions like the hippocampus are widely believed to provide the neural substrate for long-term associative memory formation. However, the experimental data are equivocal at best and may suggest a more nuanced role for NMDARs and synaptic plasticity in memory. Much of the experimental data available comes from studies in genetically modified mice in which NMDAR subunits have been deleted or mutated in order to disrupt NMDAR function. Behavioral assessment of long-term memory in these mice has involved tests like the Morris watermaze and the radial arm maze. Here we describe these behavioral tests and some of the different testing protocols that can be used to assess memory performance. We discuss the importance of distinguishing selective effects on learning and memory processes from nonspecific effects on sensorimotor or motivational aspects of performance.

Social complexity affects cognitive abilities but not brain structure in a Poeciliid fish.

Some cognitive abilities are suggested to be the result of a complex social life, allowing individuals to achieve higher fitness through advanced strategies. However, most evidence is correlative. Here, we provide an experimental investigation of how group size and composition affect brain and cognitive development in the guppy (Poecilia reticulata). For 6 months, we reared sexually mature females in one of 3 social treatments: a small conspecific group of 3 guppies, a large heterospecific group of 3 guppies and 3 splash tetras (Copella arnoldi)-a species that co-occurs with the guppy in the wild, and a large conspecific group of 6 guppies. We then tested the guppies' performance in self-control (inhibitory control), operant conditioning (associative learning), and cognitive flexibility (reversal learning) tasks. Using X-ray imaging, we measured their brain size and major brain regions. Larger groups of 6 individuals, both conspecific and heterospecific groups, showed better cognitive flexibility than smaller groups but no difference in self-control and operant conditioning tests. Interestingly, while social manipulation had no significant effect on brain morphology, relatively larger telencephalons were associated with better cognitive flexibility. This suggests alternative mechanisms beyond brain region size enabled greater cognitive flexibility in individuals from larger groups. Although there is no clear evidence for the impact on brain morphology, our research shows that living in larger social groups can enhance cognitive flexibility. This indicates that the social environment plays a role in the cognitive development of guppies.

Deep brain stimulation of the subthalamic nucleus restores spatial reversal learning in patients with Parkinson's disease.

Spatial learning and navigation are supported by distinct memory systems in the human brain such as the hippocampus-based navigational system and the striatum-cortex-based system involved in motor sequence, habit and reversal learning. Here, we studied the role of subthalamic circuits in hippocampus-associated spatial memory and striatal-associated spatial reversal learning formation in patients with Parkinson's disease, who underwent a deep brain stimulation of the subthalamic nucleus. Deep brain stimulation patients (Parkinson's disease-subthalamic nucleus: n = 26) and healthy subjects (n = 15) were tested in a novel experimental spatial memory task based on the Morris water maze that assesses both hippocampal place memory as well as spatial reversal learning. All subjects were trained to navigate to a distinct spatial location hidden within the virtual environment during 16 learning trials in a subthalamic nucleus Stim-On condition. Patients were then randomized into two groups with either a deep brain stimulation On or Off condition. Four hours later, subjects were retested in a delayed recall and reversal learning condition. The reversal learning was realized with a new hidden location that should be memorized during six consecutive trials. The performance was measured by means of an index indicating the improvement during the reversal learning. In the delayed recall condition, neither patients, healthy subjects nor the deep brain stimulation On- versus Off groups showed a difference in place memory performance of the former trained location. In the reversal learning condition, healthy subjects (reversal index 2.0) and patients in the deep brain stimulation On condition (reversal index 1.6) showed a significant improvement. However, patients in the deep brain stimulation Off condition (reversal index 1.1) performed significantly worse and did not improve. There were no differences between all groups in a final visual guided navigation task with a visible target. These results suggest that deep brain stimulation of subthalamic nucleus restores spatial reversal learning in a virtual navigation task in patients with Parkinson's disease and gives insight into the neuromodulation effects on cognition of subthalamic circuits in Parkinson's disease.

Cognitive training of mice attenuates age-related decline in associative learning and behavioral flexibility.

Identifying factors that influence age-related cognitive decline is crucial, given its severe personal and societal impacts. However, studying aging in human or animal models is challenging due to the significant variability in aging processes among individuals. Additionally, longitudinal and cross-sectional studies often produce differing results. In this context, home-cage-based behavioral analysis over lifespans has emerged as a significant method in recent years. This study aimed to explore how prior experience affects cognitive performance in mice of various age groups (4, 12, and 22 months) using a home-cage-based touchscreen test battery. In this automated system, group-housed, ID-chipped mice primarily obtain their food during task performance throughout the day, motivated by their own initiative, without being subjected to food deprivation. Spatial working memory and attention were evaluated using the trial unique non-matching to location (TUNL) and the five-choice serial reaction time task (5-CSRTT), respectively. The same set of mice learned both of these demanding tasks. While signs of cognitive decline were already apparent in middle-aged mice, older mice exhibited poorer performance in both tasks. Mice at both 12 and 22 months displayed an increase in perseverance and a decrease in the percentage of correct responses in the TUNL test compared to the 4-month-old mice. Furthermore, during the 5-CSRTT, they exhibited higher rates of omissions and premature responses compared to their younger counterparts. Additionally, the correct response rate in 22-month-old mice was lower than that of the 4-month-old ones. However, mice that had undergone cognitive training at 4 months maintained high-performance levels when re-tested at 12 months, showing an increase in correct responses during TUNL testing compared to their untrained controls. In the 5-CSRTT, previously trained mice demonstrated higher correct response rates, fewer omissions, and reduced premature responses compared to naive control mice. Notably, even when assessed on a visual discrimination and behavioral flexibility task at 22 months, experienced mice outperformed naive 4-month-old mice. These findings highlight the advantages of early-life cognitive training and suggest that its benefits extend beyond the cognitive domains primarily targeted during early training. The success of this study was significantly aided by the fully automated home-cage-based testing system, which allows for high throughput with minimal human intervention.

Serial reversal learning in nectar-feeding bats.

We explored the behavioral flexibility of Commissaris's long-tongued bats through a spatial serial reversal foraging task. Bats kept in captivity for short periods were trained to obtain nectar rewards from two artificial flowers. At any given time, only one of the flowers provided rewards and these reward contingencies reversed in successive blocks of 50 flower visits. All bats detected and responded to reversals by making most of their visits to the currently active flower. As the bats experienced repeated reversals, their preference re-adjusted faster. Although the flower state reversals were theoretically predictable, we did not detect anticipatory behavior, that is, frequency of visits to the alternative flower did not increase within each block as the programmed reversal approached. The net balance of these changes was a progressive improvement in performance in terms of the total proportion of visits allocated to the active flower. The results are compatible with, but do not depend on, the bats displaying an ability to 'learn to learn' and show that the dynamics of allocation of effort between food sources can change flexibly according to circumstances.