Visual Reversal Learning Research Articles

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.

Phencyclidine-induced cognitive impairments in repeated touchscreen visual reversal learning tests in rats

Reversal learning, a component of executive functioning, is commonly impaired among schizophrenia patients and is lacking effective treatment. N-methyl-ᴅ-aspartate (NMDA) receptor antagonists, such as phencyclidine (PCP), impair reversal learning of rodents. Touchscreen-based pairwise visual discrimination and reversal test is a translational tool to assess reversal learning in rodents. However, to fully exploit this task in testing of novel compounds, it is necessary to perform several reversal learning experiments with trained animals. Firstly, we assessed whether PCP-induced deficits in visual reversal learning in rats would be detectable with a short (5 sessions) reversal learning phase, and whether the short reversal phases could be repeated with novel stimulus pairs. Secondly, we assessed whether the PCP-induced deficits in reversal learning could be seen upon repeated PCP challenges with the same animals. Finally, we tested the effect of a novel compound, a selective α2C adrenoceptor antagonist, ORM-13070, to reverse PCP-induced cognitive deficits in this model. A 4-day PCP treatment at a dose of 1.5 mg/kg/day impaired early reversal learning in male Lister Hooded rats without inducing non-specific behavioral effects. We repeated the reversal learning experiment four times using different stimulus pairs with the same animals, and the PCP-induced impairment was evident in every single experiment. The α2C adrenoceptor antagonist ameliorated the PCP-induced cognitive deficits. Our results suggest that repeated PCP challenges in the touchscreen set-up induce schizophrenia-like cognitive deficits in visual reversal learning, improve throughput of the test and provide a protocol for testing novel drugs.

Glutamatergic and Serotonergic Modulation of Rat Medial and Lateral Orbitofrontal Cortex in Visual Serial Reversal Learning.

Adapting behavior to a dynamic environment requires both steadiness when the environment is stable and behavioral flexibility in response to changes. Much evidence suggests that cognitive flexibility, which can be operationalized in reversal learning tasks, is mediated by cortico-striatal circuitries, with the orbitofrontal cortex (OFC) playing a prominent role. The OFC is a functionally heterogeneous region, and we have previously reported differential roles of lateral (lOFC) and medial (mOFC) regions in a touchscreen serial visual reversal learning task for rats using pharmacological inactivation. Here, we investigated the effects of pharmacological overactivation of these regions using a glutamate transporter 1 (GLT-1) inhibitor, dihydrokainate (DHK), which increases extracellular glutamate by blocking its reuptake. We also tested the impact of antagonism of the serotonin 2A receptor (5-HT2AR), which modulates glutamate action, in the mOFC and lOFC on the same task. Overactivation induced by DHK produced dissociable effects in the mOFC and lOFC, with more prominent effects in the mOFC, specifically improving performance in the early, perseveration phase. Intra-lOFC DHK increased the number of omitted responses without affecting errors. In contrast, blocking the 5-HT2AR in the lOFC impaired reversal learning overall, while mOFC 5-HT2AR blockade had no effect. These results further support dissociable roles of the rodent mOFC and lOFC in deterministic visual reversal learning and indicate that modulating glutamate transmission through blocking the GLT-1 and the 5-HT2AR have different roles in these two structures.

Dorsal and ventral striatal dopamine D1 and D2 receptors differentially modulate distinct phases of serial visual reversal learning

Impaired cognitive flexibility in visual reversal-learning tasks has been observed in a wide range of neurological and neuropsychiatric disorders. Although both human and animal studies have implicated striatal D2-like and D1-like receptors (D2R; D1R) in this form of flexibility, less is known about the contribution they make within distinct sub-regions of the striatum and the different phases of visual reversal learning. The present study investigated the involvement of D2R and D1R during the early (perseverative) phase of reversal learning as well as in the intermediate and late stages (new learning) after microinfusions of D2R and D1R antagonists into the nucleus accumbens core and shell (NAcC; NAcS), the anterior and posterior dorsomedial striatum (DMS) and the dorsolateral striatum (DLS) on a touchscreen visual serial reversal-learning task. Reversal learning was improved after dopamine receptor blockade in the nucleus accumbens; the D1R antagonist, SCH23390, in the NAcS and the D2R antagonist, raclopride, in the NAcC selectively reduced early, perseverative errors. In contrast, reversal learning was impaired by D2R antagonism, but not D1R antagonism, in the dorsal striatum: raclopride increased errors in the intermediate phase after DMS infusions, and increased errors across phases after DLS infusions. These findings indicate that D1R and D2R modulate different stages of reversal learning through effects localised to different sub-regions of the striatum. Thus, deficits in behavioral flexibility observed in disorders linked to dopamine perturbations may be attributable to specific D1R and D2R dysfunction in distinct striatal sub-regions.

Supplemental Material for Glutamatergic and Serotonergic Modulation of Rat Medial and Lateral Orbitofrontal Cortex in Visual Serial Reversal Learning

Supplemental Material for Glutamatergic and Serotonergic Modulation of Rat Medial and Lateral Orbitofrontal Cortex in Visual Serial Reversal Learning

Dissociable and Paradoxical Roles of Rat Medial and Lateral Orbitofrontal Cortex in Visual Serial Reversal Learning.

ABSTRACTMuch evidence suggests that reversal learning is mediated by cortico-striatal circuitries with the orbitofrontal cortex (OFC) playing a prominent role. The OFC is a functionally heterogeneous region, but potential differential roles of lateral (lOFC) and medial (mOFC) portions in visual reversal learning have yet to be determined. We investigated the effects of pharmacological inactivation of mOFC and lOFC on a deterministic serial visual reversal learning task for rats. For reference, we also targeted other areas previously implicated in reversal learning: prelimbic (PrL) and infralimbic (IL) prefrontal cortex, and basolateral amygdala (BLA). Inactivating mOFC and lOFC produced opposite effects; lOFC impairing, and mOFC improving, performance in the early, perseverative phase specifically. Additionally, mOFC inactivation enhanced negative feedback sensitivity, while lOFC inactivation diminished feedback sensitivity in general. mOFC and lOFC inactivation also affected novel visual discrimination learning differently; lOFC inactivation paradoxically improved learning, and mOFC inactivation had no effect. We also observed dissociable roles of the OFC and the IL/PrL. Whereas the OFC inactivation affected only perseveration, IL/PrL inactivation improved learning overall. BLA inactivation did not affect perseveration, but improved the late phase of reversal learning. These results support opponent roles of the rodent mOFC and lOFC in deterministic visual reversal learning.

Dopamine D2-like receptor stimulation blocks negative feedback in visual and spatial reversal learning in the rat: behavioural and computational evidence

RationaleDopamine D2-like receptors (D2R) are important drug targets in schizophrenia and Parkinson’s disease, but D2R ligands also cause cognitive inflexibility such as poor reversal learning. The specific role of D2R in reversal learning remains unclear.ObjectivesWe tested the hypotheses that D2R agonism impairs reversal learning by blocking negative feedback and that antagonism of D1-like receptors (D1R) impairs learning from positive feedback.MethodsMale Lister Hooded rats were trained on a novel visual reversal learning task. Performance on “probe trials”, during which the correct or incorrect stimulus was presented with a third, probabilistically rewarded (50% of trials) and therefore intermediate stimulus, revealed individual learning curves for the processes of positive and negative feedback. The effects of D2R and D1R agonists and antagonists were evaluated. A separate cohort was tested on a spatial probabilistic reversal learning (PRL) task after D2R agonism. Computational reinforcement learning modelling was applied to choice data from the PRL task to evaluate the contribution of latent factors.ResultsD2R agonism with quinpirole dose-dependently impaired both visual reversal and PRL. Analysis of the probe trials on the visual task revealed a complete blockade of learning from negative feedback at the 0.25 mg/kg dose, while learning from positive feedback was intact. Estimated parameters from the model that best described the PRL choice data revealed a steep and selective decrease in learning rate from losses. D1R antagonism had a transient effect on the positive probe trials.ConclusionsD2R stimulation impairs reversal learning by blocking the impact of negative feedback.

Sex differences in color discrimination and serial reversal learning in mollies and guppies.

Behavioral flexibility provides an individual with the ability to adapt its behavior in response to environmental changes. Studies on mammals, birds, and teleosts indicate greater behavioral flexibility in females. Conversely, males appear to exhibit greater behavioral persistence. We, therefore, investigated sex differences in behavioral flexibility in 2 closely related molly species (Poecilia latipinna, P. mexicana) and their more distant relative, the guppy P. reticulata by comparing male and female individuals in a serial, visual reversal learning task. Fish were first trained in color discrimination, which was quickly learned by all females (guppies and mollies) and all molly males alike. Despite continued training over more than 72 sessions, male guppies did not learn the general test procedure and were, therefore, excluded from further testing. Once the reward contingency was reversed serially, molly males of both species performed considerably better by inhibiting their previous response and reached the learning criterion significantly faster than their respective conspecific females. Moreover, Atlantic molly males clearly outperformed all other individuals (males and females) and some of them even reached the level of 1-trial learning. Thus, the apparently universal pattern of higher female behavioral flexibility seems to be inverted in the 2 examined molly species, although the evolutionary account of this pattern remains highly speculative. These findings were complemented by the observed lower neophobia of female sailfin mollies compared with their male conspecifics. This sex difference was not observed in Atlantic mollies that were observed to be significantly less distressed in a novel situation than their consexuals. Hypothetically, sex differences in behavioral flexibility can possibly be explained in terms of the different roles that males and females play in mating competition, mate choice, and reproduction or, more generally, in complex social interactions. Each of these characteristics clearly differed between the closely related mollies and the more distantly related guppies.

Hop-Derived Iso-α-Acids in Beer Improve Visual Discrimination and Reversal Learning in Mice as Assessed by a Touch Panel Operant System.

Dementia and cognitive decline have become worldwide health problems due to rapid growth of the aged population in many countries. We previously demonstrated that single or short-term administration of iso-α-acids, hop-derived bitter acids in beer, improves the spatial memory of scopolamine-induced amnesia model mice in the Y-maze and enhances novel object recognition in normal mice via activation of the vagus nerve and hippocampal dopaminergic system. However, these behavioral tests do not replicate the stimulus conditions or response requirements of human memory tests, and so may have poor translational validity. In this report, we investigated the effects of iso-α-acids on visual discrimination (VD) and reversal discrimination (RD) using a touch panel-based operant system similar to that used for human working memory tests. In the VD task, scopolamine treatment reduced correct response rate and prolonged response latency in mice, deficits reversed by prior oral administration of iso-α-acids. In the RD task, administration of iso-α-acids significantly increased correct response rate compared to vehicle administration. Previous studies have reported that dopamine signaling is involved in both VD and RD learning, suggesting that enhancement of dopamine release contributes to improved memory performance in mice treated with iso-α-acids. Taken together, iso-α-acids improve VD and RD learning, which are considered high-order cognitive functions. Given the translational advantages of the touch panel-based operant system, the present study suggests that iso-α-acids could be effective for improvement of working memory in human dementia patients.

The Effect of Low Protein Energy-Rich Diets on Plasma Hepatic Markers, Hepatic Damage, and Discrimination Reversal Learning in Young Female Chicks.

Consumption of low protein energy-rich (LPER) diets increases susceptibility to metabolic disease in mammals, such as hepatic damage, and can have an adverse effect on cognition. However, the effects of these diets on both physical and mental welfare have not been investigated in domestic meat chickens. Female chicks received a low protein energy-rich or a standard control diet from 21 to 51 days of age. The effects of these dietary manipulations on plasma hepatic markers for liver damage, liver necropsy, and learning a visual discrimination reversal task were assessed. Birds given access to LPER diets weighed less than chicks that had access to the control diets. All chicks had post-mortem signs of hepatic hemorrhage/increased liver color scores and aspartate aminotransferase (AST) levels above 230 U/L indicative of hepatic damage in birds. The LPER diet had no impact on the performance of female chicks when learning to distinguish colors in a reversal visual discrimination task. The present study suggests that liver damage does not become worse when feeding LPER or impact visual reversal learning in female meat-type chickens. However, the high incidence of liver cell damage/liver hemorrhage, and “abnormal” AST activities are of concern in female broiler chicks across both diets, and suggests that the health of modern meat-type genotypes needs to be improved.

Selective effects of 5-HT2C receptor modulation on performance of a novel valence-probe visual discrimination task and probabilistic reversal learning in mice

RationaleDysregulation of the serotonin (5-HT) system is a pathophysiological component in major depressive disorder (MDD), a condition closely associated with abnormal emotional responsivity to positive and negative feedback. However, the precise mechanism through which 5-HT tone biases feedback responsivity remains unclear. 5-HT2C receptors (5-HT2CRs) are closely linked with aspects of depressive symptomatology, including abnormalities in reinforcement processes and response to stress. Thus, we aimed to determine the impact of 5-HT2CR function on response to feedback in biased reinforcement learning.MethodsWe used two touchscreen assays designed to assess the impact of positive and negative feedback on probabilistic reinforcement in mice, including a novel valence-probe visual discrimination (VPVD) and a probabilistic reversal learning procedure (PRL). Systemic administration of a 5-HT2CR agonist and antagonist resulted in selective changes in the balance of feedback sensitivity bias on these tasks.ResultsSpecifically, on VPVD, SB 242084, the 5-HT2CR antagonist, impaired acquisition of a discrimination dependent on appropriate integration of positive and negative feedback. On PRL, SB 242084 at 1 mg/kg resulted in changes in behaviour consistent with reduced sensitivity to positive feedback. In contrast, WAY 163909, the 5-HT2CR agonist, resulted in changes associated with increased sensitivity to positive feedback and decreased sensitivity to negative feedback.ConclusionsThese results suggest that 5-HT2CRs tightly regulate feedback sensitivity bias in mice with consequent effects on learning and cognitive flexibility and specify a framework for the influence of 5-HT2CRs on sensitivity to reinforcement.

Reconsideration of Serial Visual Reversal Learning in Octopus (Octopus vulgaris) from a Methodological Perspective.

Octopuses (Octopus vulgaris) are generally considered to possess extraordinary cognitive abilities including the ability to successfully perform in a serial reversal learning task. During reversal learning, an animal is presented with a discrimination problem and after reaching a learning criterion, the signs of the stimuli are reversed: the former positive becomes the negative stimulus and vice versa. If an animal improves its performance over reversals, it is ascribed advanced cognitive abilities. Reversal learning has been tested in octopus in a number of studies. However, the experimental procedures adopted in these studies involved pre-training on the new positive stimulus after a reversal, strong negative reinforcement or might have enabled secondary cueing by the experimenter. These procedures could have all affected the outcome of reversal learning. Thus, in this study, serial visual reversal learning was revisited in octopus. We trained four common octopuses (O. vulgaris) to discriminate between 2-dimensional stimuli presented on a monitor in a simultaneous visual discrimination task and reversed the signs of the stimuli each time the animals reached the learning criterion of ≥80% in two consecutive sessions. The animals were trained using operant conditioning techniques including a secondary reinforcer, a rod that was pushed up and down the feeding tube, which signaled the correctness of a response and preceded the subsequent primary reinforcement of food. The experimental protocol did not involve negative reinforcement. One animal completed four reversals and showed progressive improvement, i.e., it decreased its errors to criterion the more reversals it experienced. This animal developed a generalized response strategy. In contrast, another animal completed only one reversal, whereas two animals did not learn to reverse during the first reversal. In conclusion, some octopus individuals can learn to reverse in a visual task demonstrating behavioral flexibility even with a refined methodology.

Touch-screen visual reversal learning is mediated by value encoding and signal propagation in the orbitofrontal cortex

Behavioral inflexibility is a common symptom of neuropsychiatric disorders which can have a major detrimental impact on quality of life. While the orbitofrontal cortex (OFC) has been strongly implicated in behavioral flexibility in rodents across paradigms, our understanding of how the OFC mediates these behaviors is rapidly adapting. Here we examined neuronal activity during reversal learning by coupling in vivo electrophysiological recording with a mouse touch-screen learning paradigm to further elucidate the role of the OFC in updating reward value. Single unit and oscillatory activity was recorded during well-learned discrimination and 3 distinct phases of reversal (early, chance and well-learned). During touch-screen performance, OFC neuronal firing tracked rewarded responses following a previous rewarded choice when behavior was well learned, but shifted to primarily track repeated errors following a previous error in early reversal. Spike activity tracked rewarded choices independent of previous trial outcome during chance reversal, and returned to the initial pattern of reward response at criterion. Analysis of spike coupling to oscillatory local field potentials showed that less frequently occurring behaviors had significantly fewer neurons locked to any oscillatory frequency. Together, these data support the role of the OFC in tracking the value of individual choices to inform future responses and suggests that oscillatory signaling may be involved in propagating responses to increase or decrease the likelihood that action is taken in the future. They further support the use of touch-screen paradigms in preclinical studies to more closely model clinical approaches to measuring behavioral flexibility.

EP 21. Neuromodulation of the hyperdirect pathway to study flexibility as an endophenotype of obsessive compulsive disorders

Obsessive-Compulsive Disorder (OCD) is a mental disorder featuring obsessions (intrusive ideas) and compulsions which are repetitive behaviors performed through rigid rituals. This phenomenological observation has led to explore the idea that OCD patients have diminished behavioral flexibility. The pathophysiology of OCD support this hypothesis with dysfunctional cortico-basal ganglia loops including two specific structures connected together through the hyperdirect pathway: the subthalamic nucleus and the orbitofrontal cortex, both also involved in behavioral flexibility. Thus, our objective is twofold: to verify the involvement of behavioral flexibility in the compulsive behavior and to explore the neurobiological bases underlying flexibility in patients and an animal model of OCD (SAPAP3-KO). We aim at developing similar behavioral tasks in both species where we could chronically modulate neural activity using deep brain stimulation and optogenetic. Behavioral flexibility may be challenged in reversal learning paradigms. In these tasks, the subject has to respond to either of two different visual stimuli but only one stimulus is positively rewarded while the other is not. When the association has been learned, reward contingencies are inverted. This task has been implemented easily for neuropsychological studies in human. However, the adaptation of non-spatial reversal learning task in rodents is much more laborious due to the high number of trials required for the acquisition. To overcome this issue, we developed automated behavioral cages where animals could live and be exposed continuously to the reversal learning task. Our protocol is based on 5 main successive stages of training and allow to perform multiple reversal within one session. This experimental setup has also be designed to integrate chronic neuronal stimulation device to automatically modulate neural activity in the hyperdirect pathway during relevant events of the task. We succeeded in designing a similar reversal learning task to explore the behavioral flexibility both in humans and rodents. With our automatic ecological behavioral setup for mice, we reduced very significantly the time necessary to perform visual reversal learning task compared to more classical paradigm. Moreover we obtained preliminary results which are in line with the hypothesis of an impaired behavioral flexibility in compulsive subjects. Indeed, we observed that both OCD patients and SAPAP3-KO mice showed perseverative maladaptive behaviors in our task. These preliminary results suggest that OCD conditions could be associated with a diminished behavioral flexibility. The development of a translational behavioral task is the first step of our aim to explore the neural basis of the behavioral flexibility and its link with compulsive behavior. For this purpose, our innovative designs will allow us to modulate the cortico-basal ganglia pathways both in patients (with DBS) and OCD mouse model (with optogenetic) during behavioral tasks to study their implications in compulsive behaviors.

The role of 5-HT2C receptors in touchscreen visual reversal learning in the rat: a cross-site study.

RationaleReversal learning requires associative learning and executive functioning to suppress non-adaptive responding. Reversal-learning deficits are observed in e.g. schizophrenia and obsessive-compulsive disorder and implicate neural circuitry including the orbitofrontal cortex (OFC). Serotonergic function has been strongly linked to visual reversal learning in humans and experimental animals but less is known about which receptor subtypes are involved.ObjectivesThe objectives of the study were to test the effects of systemic and intra-OFC 5-HT2C-receptor antagonism on visual reversal learning in rats and assess the psychological mechanisms underlying these effects within novel touchscreen paradigms.MethodsIn experiments 1–2, we used a novel 3-stimulus task to investigate the effects of 5-HT2C-receptor antagonism through SB 242084 (0.1, 0.5 and 1.0 mg/kg i.p.) cross-site. Experiment 3 assessed the effects of SB 242084 in 2-choice reversal learning. In experiment 4, we validated a novel touchscreen serial visual reversal task suitable for neuropharmacological microinfusions by baclofen-/muscimol-induced OFC inactivation. In experiment 5, we tested the effect of intra-OFC SB 242084 (1.0 or 3.0 μg/side) on performance in this task.ResultsIn experiments 1–3, SB 242084 reduced early errors but increased late errors to criterion. In experiment 5, intra-OFC SB 242084 reduced early errors without increasing late errors in a reversal paradigm validated as OFC dependent (experiment 4).ConclusionIntra-OFC 5-HT2C-receptor antagonism decreases perseveration in novel touchscreen reversal-learning paradigms for the rat. Systemic 5-HT2C-receptor antagonism additionally impairs late learning—a robust effect observed cross-site and potentially linked to impulsivity. These conclusions are discussed in terms of neural mechanisms underlying reversal learning and their relevance to psychiatric disorders.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-015-3963-5) contains supplementary material, which is available to authorized users.

Simple Discrimination and Reversal Learning Sets in Typically Developing Young Children

The present study investigated the acquisition of visual simple discrimination and reversal learning sets using intermixed discrimination training (i.e., two or more pairs of stimuli presented in the same session) in 2-year-old typically developing children. An additional purpose was to investigate the effects of the procedure on the production of functional classes. The study was a systematic replication of previous research conducted with preschool children. Three children participated in the study. The participants were initially exposed to simple discrimination training with two pairs of stimuli in separate sessions. The next phase involved intermixed discrimination training in which the two pairs of stimuli (A and B) were presented in the same session. After the criterion was reached, the children were exposed to repeated reversals with Pairs A and B. Two participants were exposed to an adaptation of the blocked-trial procedure before being exposed to sessions that presented the stimuli in a random sequence. The same sequence was conducted with three additional pairs of stimuli (C, D, and E), with the exception that all of the participants were exposed to the procedure without the blocked-trial procedure. The results indicated that all of the children learned discriminations and showed decreases in the number of sessions to reach the criterion and errors. The blocked-trial procedure was effective in producing errorless learning during the initial intermixed discriminations. However, during repeated reversals, the effects of the blocked-trial procedure were not so clear, since performance was influenced by motivational and other procedural variables. All three participants showed evidence of functional class formation in some of the reversal phases. Functional class formation was also influenced by the occurrence of errors and motivational variables.

Accelerated behavioural development changes fine-scale search behaviour and spatial memory in honey bees (Apis mellifera L.).

Normally, worker honey bees (Apis mellifera) begin foraging when more than 2weeks old as adults, but if individual bees or the colony is stressed, bees often begin foraging precociously. Here, we examined whether bees that accelerated their behavioural development to begin foraging precociously differed from normal-aged foragers in cognitive performance. We used a social manipulation to generate precocious foragers from small experimental colonies and tested their performance in a free-flight visual reversal learning task, and a test of spatial memory. To assess spatial memory, bees were trained to learn the location of a small sucrose feeder within an array of three landmarks. In tests, the feeder and one landmark were removed and the search behaviour of the bees was recorded. Performance of precocious and normal-aged foragers did not differ in a visual reversal learning task, but the two groups showed a clear difference in spatial memory. Flight behaviour suggested normal-aged foragers were better able to infer the position of the removed landmark and feeder relative to the remaining landmarks than precocious foragers. Previous studies have documented the cognitive decline of old foragers, but this is the first suggestion of a cognitive deficit in young foragers. These data imply that worker honey bees continue their cognitive development during the adult stage. These findings may also help to explain why precocious foragers perform quite poorly as foragers and have a higher than normal loss rate.

A GABAergic Inhibitory Neural Circuit Regulates Visual Reversal Learning inDrosophila

Inflexible cognition and behavior are prominent features of prefrontal cortex damage and several neuropsychiatric disorders. The ability to flexibly adapt cognitive processing and behavior to dynamically changing environmental contingencies has been studied using the reversal learning paradigm in mammals, but the complexity of the brain circuits precludes a detailed analysis of the underlying neural mechanism. Here we study the neural circuitry mechanism supporting flexible behavior in a genetically tractable model organism, Drosophila melanogaster. Combining quantitative behavior analysis and genetic manipulation, we found that inhibition from a single pair of giant GABAergic neurons, the anterior paired lateral (APL) neurons, onto the mushroom bodies (MBs) selectively facilitates behavioral flexibility during visual reversal learning. This effect was mediated by ionotropic GABA(A) receptors in the MB. Moreover, flies with perturbed MB output recapitulated the poor reversal performance of flies with dysfunctional APL neurons. Importantly, we observed that flies with dysfunctional APL-MB circuit performed normally in simple forms of visual learning, including initial learning, extinction, and differential conditioning. Finally, we showed that acute disruption of the APL-MB circuit is sufficient to impair visual reversal learning. Together, these data suggest that the APL-MB circuit plays an essential role in the resolution of conflicting reinforcement contingencies and reveals an inhibitory neural mechanism underlying flexible behavior in Drosophila.

Improved cognitive flexibility in serotonin transporter knockout rats is unchanged following chronic cocaine self‐administration

Cocaine dependence is associated with orbitofrontal cortex (OFC)-dependent cognitive inflexibility in both humans and laboratory animals. A critical question is whether cocaine self-administration affects pre-existing individual differences in cognitive flexibility. Serotonin transporter knockout (5-HTT(-/-) ) mice show improved cognitive flexibility in a visual reversal learning task, whereas 5-HTT(-/-) rats self-administer increased amounts of cocaine. Here we assessed: (1) whether 5-HTT(-/-) rats also show improved cognitive flexibility (next to mice); and (2) whether this is affected by cocaine self-administration, which is increased in these animals. Results confirmed that naïve 5-HTT(-/-) rats (n = 8) exhibit improved cognitive flexibility, as measured in a sucrose reinforced reversal learning task. A separate group of rats was subsequently trained to intravenously self-administer cocaine (0.5 mg/kg/infusion), and we observed that the 5-HTT(-/-) rats (n = 10) self-administered twice as much cocaine [632.7 mg/kg (±26.3)] compared with 5-HTT(+/+) rats (n = 6) [352.3 mg/kg (±62.0)] over 50 1-hour sessions. Five weeks into withdrawal the cocaine-exposed animals were tested in the sucrose-reinforced reversal learning paradigm. Interestingly, like the naïve 5-HTT(-/-) rats, the cocaine exposed 5-HTT(-/-) rats displayed improved cognitive flexibility. In conclusion, we show that improved reversal learning in 5-HTT(-/-) rats reflects a pre-existing trait that is preserved during cocaine-withdrawal. As 5-HTT(-/-) rodents model the low activity s-allele of the human serotonin transporter-linked polymorphic region, these findings may have heuristic value in the treatment of s-allele cocaine addicts.

Stimulus specific deficit on visual reversal learning after lesions of medial prefrontal cortex in the mouse

Tests of executive abilities, such as discrimination reversal and attentional set shifting, are sensitive to prefrontal cortex (PFC) damage in primates. The purpose of the present study was to use a primate reversal task to determine if PFC in the mouse is involved in similar cognitive functions. Mice with lesions of medial PFC and Sham operated control animals were trained on a series of visual problems in a computer-automated touchscreen apparatus using stimuli that varied in either pattern (lines) or luminance (black–white). PFC-lesioned mice learned to discriminate both sets of stimuli as readily as controls, but displayed a stimulus specific (pattern only) deficit on the reversal task. Analysis of error patterns on the line reversal suggests the deficit exhibited by PFC-lesioned mice was related to stimulus specific aspects of visual attention, rather than perseveration. These results demonstrate that medial PFC may play a role in control of directed attention and provide further evidence that the touchscreen procedure can be a useful tool for examining functional similarities in brain regions of very diverse species.