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1.
Sci Rep ; 14(1): 10187, 2024 05 03.
Article in English | MEDLINE | ID: mdl-38702381

ABSTRACT

Neurexins (Nrxns) are critical for synapse organization and their mutations have been documented in autism spectrum disorder, schizophrenia, and epilepsy. We recently reported that conditional deletion of Nrxn2, under the control of Emx1Cre promoter, predominately expressed in the neocortex and hippocampus (Emx1-Nrxn2 cKO mice) induced stereotyped patterns of behavior in mice, suggesting behavioral inflexibility. In this study, we investigated the effects of Nrxn2 deletion through two different conditional approaches targeting presynaptic cortical neurons projecting to dorsomedial striatum on the flexibility between goal-directed and habitual actions in response to devaluation of action-outcome (A-O) contingencies in an instrumental learning paradigm or upon reversal of A-O contingencies in a water T-maze paradigm. Nrxn2 deletion through both the conditional approaches induced an inability of mice to discriminate between goal-directed and habitual action strategies in their response to devaluation of A-O contingency. Emx1-Nrxn2 cKO mice exhibited reversal learning deficits, indicating their inability to adopt new action strategies. Overall, our studies showed that Nrxn2 deletion through two distinct conditional deletion approaches impaired flexibility in response to alterations in A-O contingencies. These investigations can lay the foundation for identification of novel genetic factors underlying behavioral inflexibility.


Subject(s)
Behavior, Animal , Mice, Knockout , Nerve Tissue Proteins , Transcription Factors , Animals , Mice , Nerve Tissue Proteins/genetics , Male , Neural Cell Adhesion Molecules/genetics , Gene Deletion , Maze Learning/physiology , Reversal Learning/physiology , Homeodomain Proteins/genetics , Hippocampus/metabolism , Cell Adhesion Molecules, Neuronal/genetics , Conditioning, Operant
2.
Sci Rep ; 14(1): 8443, 2024 04 10.
Article in English | MEDLINE | ID: mdl-38600127

ABSTRACT

Flexibly updating behaviors towards others is crucial for adaptive social functioning. Previous studies have found that difficulties in flexibly updating behaviors are associated with social anxiety (SA). However, it is unclear whether such difficulties relate to actual social behaviors. The current study investigated the relationships between negative-to-positive social reversal learning, social approach behavior, and SA across time. Participants (MTurk, Time 1 = 275, Time 2 = 126, 16 weeks later) completed a performance-based social reversal-learning task. In the initial phase, participants learned that interactions with certain individuals are associated with negative outcomes, whereas interactions with other individuals are associated with positive outcomes. In the reversal phase, these associations were reversed, requiring participants to update their behaviors. The relationships between the performance in the task, SA severity, and social approach behavior reported by participants were assessed cross-sectionally and longitudinally. We found that negative-to-positive updating was negatively associated with SA severity. Furthermore, negative-to-positive updating was positively correlated with social approach behavior, both cross-sectionally and prospectively. Hence, individuals with better negative-to-positive updating at Time 1 reported significantly more social approach behaviors across time. The results support the role of negative-to-positive updating as a mechanism associated with SA and social approach, advancing and refining interpersonal and cognitive theories of SA.


Subject(s)
Reversal Learning , Social Learning , Humans , Anxiety/psychology , Social Adjustment , Fear
3.
Sci Rep ; 14(1): 8906, 2024 04 17.
Article in English | MEDLINE | ID: mdl-38632252

ABSTRACT

People correct for movement errors when acquiring new motor skills (de novo learning) or adapting well-known movements (motor adaptation). While de novo learning establishes new control policies, adaptation modifies existing ones, and previous work have distinguished behavioral and underlying brain mechanisms for each motor learning type. However, it is still unclear whether learning in each type interferes with the other. In study 1, we use a within-subjects design where participants train with both 30° visuomotor rotation and mirror reversal perturbations, to compare adaptation and de novo learning respectively. We find no perturbation order effects, and find no evidence for differences in learning rates and asymptotes for both perturbations. Explicit instructions also provide an advantage during early learning in both perturbations. However, mirror reversal learning shows larger inter-participant variability and slower movement initiation. Furthermore, we only observe reach aftereffects following rotation training. In study 2, we incorporate the mirror reversal in a browser-based task, to investigate under-studied de novo learning mechanisms like retention and generalization. Learning persists across three or more days, substantially transfers to the untrained hand, and to targets on both sides of the mirror axis. Our results extend insights for distinguishing motor skill acquisition from adapting well-known movements.


Subject(s)
Generalization, Psychological , Psychomotor Performance , Humans , Motor Skills , Movement , Reversal Learning , Adaptation, Physiological
4.
Behav Brain Res ; 466: 114977, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38570074

ABSTRACT

Apathy is a complex psychiatric syndrome characterised by motivational deficit, emotional blunting and cognitive changes. It occurs alongside a broad range of neurological disorders, but also occurs in otherwise healthy ageing. Despite its clinical prevalence, apathy does not yet have a designated treatment strategy. Generation of a translational animal model of apathy syndrome would facilitate the development of novel treatments. Given the multidimensional nature of apathy, a model cannot be achieved with a single behavioural test. Using a battery of behavioural tests we investigated whether aged rats exhibit behavioural deficits across different domains relevant to apathy. Using the effort for reward and progressive ratio tasks we found that aged male rats (21-27 months) show intact reward motivation. Using the novelty supressed feeding test and position-based object exploration we found aged rats showed increased anxiety-like behaviour inconsistent with emotional blunting. The sucrose preference test and reward learning assay showed intact reward sensitivity and reward-related cognition in aged rats. However, using a bowl-digging version of the probabilistic reversal learning task, we found a deficit in cognitive flexibility in aged rats that did not translate across to a touchscreen version of the task. While these data reveal important changes in cognitive flexibility and anxiety associated with ageing, aged rats do not show deficits across other behavioural domains relevant to apathy. This suggests that aged rats are not a suitable model for age-related apathy syndrome. These findings contrast with previous work in mice, revealing important species differences in behaviours relevant to apathy syndrome in ageing.


Subject(s)
Aging , Anxiety , Apathy , Disease Models, Animal , Motivation , Reward , Animals , Male , Apathy/physiology , Aging/physiology , Motivation/physiology , Anxiety/physiopathology , Rats , Behavior, Animal/physiology , Reversal Learning/physiology , Exploratory Behavior/physiology
5.
Brain Behav ; 14(5): e3484, 2024 May.
Article in English | MEDLINE | ID: mdl-38680075

ABSTRACT

BACKGROUND: Living in a social dominance hierarchy presents different benefits and challenges for dominant and subordinate males and females, which might in turn affect their cognitive needs. Despite the extensive research on social dominance in group-living species, there is still a knowledge gap regarding how social status impacts brain morphology and cognitive abilities. METHODS: Here, we tested male and female dominants and subordinates of Neolamprologus pulcher, a social cichlid fish species with size-based hierarchy. We ran three executive cognitive function tests for cognitive flexibility (reversal learning test), self-control (detour test), and working memory (object permanence test), followed by brain and brain region size measurements. RESULTS: Performance was not influenced by social status or sex. However, dominants exhibited a brain-body slope that was relatively steeper than that of subordinates. Furthermore, individual performance in reversal learning and detour tests correlated with brain morphology, with some trade-offs among major brain regions like telencephalon, cerebellum, and optic tectum. CONCLUSION: As individuals' brain growth strategies varied depending on social status without affecting executive functions, the different associated challenges might yield a potential effect on social cognition instead. Overall, the findings highlight the importance of studying the individual and not just species to understand better how the individual's ecology might shape its brain and cognition.


Subject(s)
Brain , Cichlids , Executive Function , Animals , Cichlids/physiology , Cichlids/anatomy & histology , Female , Male , Executive Function/physiology , Brain/anatomy & histology , Brain/physiology , Brain/growth & development , Social Dominance , Reversal Learning/physiology , Memory, Short-Term/physiology
6.
Behav Brain Res ; 466: 115007, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38648867

ABSTRACT

Although active touch in rodents arises from the forepaws as well as whiskers, most research on active touch only focuses on whiskers. This results in a paucity of tasks designed to assess the process of active touch with a forepaw. We develop a new experimental task, the Reach-to-Grasp and Tactile Discrimination task (RGTD task), to examine active touch with a forepaw in rodents, particularly changes in processes of active touch during motor skill learning. In the RGTD task, animals are required to (1) extend their forelimb to an object, (2) grasp the object, and (3) manipulate the grasped object with the forelimb. The animals must determine the direction of the manipulation based on active touch sensations arising during the period of the grasping. In experiment 1 of the present study, we showed that rats can learn the RGTD task. In experiment 2, we confirmed that the rats are capable of reversal learning of the RGTD task. The RGTD task shared most of the reaching movements involved with conventional forelimb reaching tasks. From the standpoint of a discrimination task, the RGTD task enables rigorous experimental control, for example by removing bias in the stimulus-response correspondence, and makes it possible to utilize diverse experimental procedures that have been difficult in prior tasks.


Subject(s)
Discrimination Learning , Forelimb , Touch , Animals , Rats , Male , Forelimb/physiology , Touch/physiology , Discrimination Learning/physiology , Hand Strength/physiology , Touch Perception/physiology , Psychomotor Performance/physiology , Discrimination, Psychological/physiology , Motor Skills/physiology , Rats, Long-Evans , Reversal Learning/physiology
7.
Anim Cogn ; 27(1): 14, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38429567

ABSTRACT

Cognitive flexibility enables animals to alter their behaviour and respond appropriately to environmental changes. Such flexibility is important in urban settings where environmental changes occur rapidly and continually. We studied whether free-living, urban-dwelling yellow mongooses, Cynictis penicillata, in South Africa, are cognitively flexible in reversal learning and attention task experiments (n = 10). Reversal learning was conducted using two puzzle boxes that were distinct visually and spatially, each containing a preferred or non-preferred food type. Once mongooses learned which box contained the preferred food type, the food types were reversed. The mongooses successfully unlearned their previously learned response in favour of learning a new response, possibly through a win-stay, lose-shift strategy. Attention task experiments were conducted using one puzzle box surrounded by zero, one, two or three objects, introducing various levels of distraction while solving the task. The mongooses were distracted by two and three distractions but were able to solve the task despite the distractions by splitting their attention between the puzzle box task and remaining vigilant. However, those exposed to human residents more often were more vigilant. We provide the first evidence of cognitive flexibility in urban yellow mongooses, which enables them to modify their behaviour to urban environments.


Subject(s)
Herpestidae , Humans , Animals , Reversal Learning , South Africa , Cognition
8.
Anim Cogn ; 27(1): 24, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38451365

ABSTRACT

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.


Subject(s)
Chiroptera , Plant Nectar , Animals , Reversal Learning , Flowers , Food
9.
Nat Commun ; 15(1): 1704, 2024 Feb 24.
Article in English | MEDLINE | ID: mdl-38402210

ABSTRACT

Outcome-guided behavior requires knowledge about the identity of future rewards. Previous work across species has shown that the dopaminergic midbrain responds to violations in expected reward identity and that the lateral orbitofrontal cortex (OFC) represents reward identity expectations. Here we used network-targeted transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) during a trans-reinforcer reversal learning task to test the hypothesis that outcome expectations in the lateral OFC contribute to the computation of identity prediction errors (iPE) in the midbrain. Network-targeted TMS aiming at lateral OFC reduced the global connectedness of the lateral OFC and impaired reward identity learning in the first block of trials. Critically, TMS disrupted neural representations of expected reward identity in the OFC and modulated iPE responses in the midbrain. These results support the idea that iPE signals in the dopaminergic midbrain are computed based on outcome expectations represented in the lateral OFC.


Subject(s)
Mesencephalon , Prefrontal Cortex , Prefrontal Cortex/physiology , Mesencephalon/physiology , Reward , Reversal Learning/physiology , Signal Transduction , Magnetic Resonance Imaging
10.
Neuropsychopharmacology ; 49(6): 1042-1049, 2024 May.
Article in English | MEDLINE | ID: mdl-38409282

ABSTRACT

The stomach-derived hormone ghrelin plays not only a role in feeding, starvation, and survival, but it has been suggested to also be involved in the stress response, in neuropsychiatric conditions, and in alcohol and drug use disorders. Mechanisms related to reward processing might mediate ghrelin's broader effects on complex behaviors, as indicated by animal studies and mostly correlative human studies. Here, using a within-subject double-blind placebo-controlled design with intravenous ghrelin infusion in healthy volunteers (n = 30), we tested whether ghrelin alters sensitivity to reward and punishment in a reward learning task. Parameters were derived from a computational model of participants' task behavior. The reversal learning task with monetary rewards was performed during functional brain imaging to investigate ghrelin effects on brain signals related to reward prediction errors. Compared to placebo, ghrelin decreased punishment sensitivity (t = -2.448, p = 0.021), while reward sensitivity was unaltered (t = 0.8, p = 0.43). We furthermore found increased prediction-error related activity in the dorsal striatum during ghrelin administration (region of interest analysis: t-values ≥ 4.21, p-values ≤ 0.044). Our results support a role for ghrelin in reward processing that extends beyond food-related rewards. Reduced sensitivity to negative outcomes and increased processing of prediction errors may be beneficial for food foraging when hungry but could also relate to increased risk taking and impulsivity in the broader context of addictive behaviors.


Subject(s)
Caudate Nucleus , Ghrelin , Punishment , Reward , Humans , Male , Ghrelin/pharmacology , Ghrelin/administration & dosage , Double-Blind Method , Adult , Young Adult , Female , Caudate Nucleus/drug effects , Caudate Nucleus/diagnostic imaging , Caudate Nucleus/metabolism , Magnetic Resonance Imaging , Reversal Learning/drug effects , Reversal Learning/physiology , Feedback, Psychological/drug effects , Feedback, Psychological/physiology
11.
Neuropharmacology ; 247: 109860, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38336243

ABSTRACT

Fetal alcohol spectrum disorder (FASD) is the most common preventable form of developmental and neurobehavioral disability. Animal models have demonstrated that even low to moderate prenatal alcohol exposure (PAE) is sufficient to impair behavioral flexibility in multiple domains. Previously, utilizing a moderate limited access drinking in the dark paradigm, we have shown that PAE 1) impairs touchscreen pairwise visual reversal in male adult offspring 2) leads to small but significant decreases in orbitofrontal (OFC) firing rates 3) significantly increases dorsal striatum (dS) activity and 4) aberrantly sustains OFC-dS synchrony across early reversal. In the current study, we examined whether optogenetic stimulation of OFC-dS projection neurons would be sufficient to rescue the behavioral inflexibility induced by PAE in male C57BL/6J mice. Following discrimination learning, we targeted OFC-dS projections using a retrograde adeno-associated virus (AAV) delivered to the dS which expressed channel rhodopsin (ChR2). During the first four sessions of reversal learning, we delivered high frequency optogenetic stimulation to the OFC via optic fibers immediately following correct choice responses. Our results show that optogenetic stimulation significantly reduced the number of sessions, incorrect responses, and correction errors required to move past the early perseverative phase for both PAE and control mice. In addition, OFC-dS stimulation during early reversal learning reduced the increased sessions, correct and incorrect responding seen in PAE mice during the later learning phase of reversal but did not significantly alter later performance in control ChR2 mice. Taken together these results suggest that stimulation of OFC-dS projections can improve early reversal learning in PAE and control mice, and these improvements can persist even into later stages of the task days later. These studies provide an important foundation for future clinical approaches to improve executive control in those with FASD. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".


Subject(s)
Fetal Alcohol Spectrum Disorders , Prenatal Exposure Delayed Effects , Humans , Mice , Male , Female , Animals , Pregnancy , Prefrontal Cortex/physiology , Optogenetics , Mice, Inbred C57BL , Prenatal Exposure Delayed Effects/psychology , Reversal Learning/physiology
12.
Atten Percept Psychophys ; 86(3): 815-827, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38418805

ABSTRACT

This study investigated whether the interference between two tasks in dual-task processing stems from bottleneck limitations or insufficient cognitive resources due to resource sharing. Experiment 1 used tone discrimination as Task 1 and word or pseudoword classification as Task 2 to evaluate the effect of automatic versus controlled processing on dual-task interference under different SOA conditions. Experiment 2 reversed the task order. The results showed that dual-task interference persisted regardless of task type or order. Neither experiment found evidence that automatic tasks could eliminate interference. This suggests that resource limitations, rather than bottlenecks, may better explain dual-task costs. Specifically, when tasks compete for limited resources, the processing efficiency of both tasks is significantly reduced. Future research should explore how cognitive resources are dynamically allocated between tasks to better account for dual-task interference effects.


Subject(s)
Attention , Reaction Time , Humans , Male , Female , Young Adult , Pitch Discrimination , Automatism/psychology , Reversal Learning , Executive Function/physiology , Semantics , Adult
13.
Nat Commun ; 15(1): 59, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38167691

ABSTRACT

The dopaminergic system is firmly implicated in reversal learning but human measurements of dopamine release as a correlate of reversal learning success are lacking. Dopamine release and hemodynamic brain activity in response to unexpected changes in action-outcome probabilities are here explored using simultaneous dynamic [11C]Raclopride PET-fMRI and computational modelling of behavior. When participants encounter reversed reward probabilities during a card guessing game, dopamine release is observed in associative striatum. Individual differences in absolute reward prediction error and sensitivity to errors are associated with peak dopamine receptor occupancy. The fMRI response to perseverance errors at the onset of a reversal spatially overlap with the site of dopamine release. Trial-by-trial fMRI correlates of absolute prediction errors show a response in striatum and association cortices, closely overlapping with the location of dopamine release, and separable from a valence signal in ventral striatum. The results converge to implicate striatal dopamine release in associative striatum as a central component of reversal learning, possibly signifying the need for increased cognitive control when new stimuli-responses should be learned.


Subject(s)
Dopamine , Ventral Striatum , Humans , Reversal Learning/physiology , Corpus Striatum/diagnostic imaging , Raclopride , Neostriatum , Ventral Striatum/diagnostic imaging , Reward
14.
Neurobiol Learn Mem ; 208: 107892, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38242226

ABSTRACT

Behavioral flexibility, one of the core executive functions of the brain, has been shown to be an essential skill for survival across species. Corticostriatal circuits play a critical role in mediating behavioral flexibility. The molecular mechanisms underlying these processes are still unclear. Here, we measured how synaptic glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-D-aspartic acid receptor (NMDAR) expression dynamically changed during specific stages of learning and reversal. Following training to well-established stages of discrimination and reversal learning on a touchscreen visual task, lateral orbitofrontal cortex (OFC), dorsal striatum (dS) as well as medial prefrontal cortex (mPFC), basolateral amygdala (BLA) and piriform cortex (Pir) were micro dissected from male mouse brain and the expression of glutamatergic receptor subunits in the synaptic fraction were measured via immunoblotting. We found that the GluN2B subunit of NMDAR in the OFC remained stable during initial discrimination learning but significantly increased in the synaptic fraction during mid-reversal stages, the period during which the OFC has been shown to play a critical role in updating outcome expectancies. In contrast, both GluA1 and GluA2 subunits of the AMPAR significantly increased in the dS synaptic fraction as new associations were learned late in reversal. Expression of NMDAR and AMPAR subunits did not significantly differ across learning stages in any other brain region. Together, these findings further support the involvement of OFC-dS circuits in moderating well-learned associations and flexible behavior and suggest that dynamic synaptic expression of NMDAR and AMPAR in these circuits may play a role in mediating efficient learning during discrimination and the ability to update previously learned associations as environmental contingencies change.


Subject(s)
Prefrontal Cortex , Reversal Learning , Mice , Male , Animals , Reversal Learning/physiology , Prefrontal Cortex/physiology , Discrimination Learning/physiology , Brain , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid , Carrier Proteins
15.
Psychopharmacology (Berl) ; 241(4): 849-863, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38062167

ABSTRACT

RATIONALE: Patients with major depressive disorder (MDD) often experience abnormalities in behavioral adaptation following environmental changes (i.e., cognitive flexibility) and tend to undervalue positive outcomes but overvalue negative outcomes. The probabilistic reversal learning task (PRL) is used to study these deficits across species and to explore drugs that may have therapeutic value. Selective serotonin-reuptake inhibitors (SSRIs) have limited effectiveness in treating MDD and produce inconsistent effects in non-human versions of the PRL. As such, ketamine, a novel and potentially rapid-acting therapeutic, has begun to be examined using the PRL. Two previous studies examining the effects of ketamine in the PRL have shown conflicting results and only examined short-term effects of ketamine. OBJECTIVE: This experiment examined PRL performance across a 2-week period following a single exposure to a ketamine dose that varied across groups. METHODS: After five sessions of PRL training, groups of rats received an injection of either 0, 10, 20 or 30 mg/kg ketamine. One-hour post-injection, rats engaged in the PRL, and subsequently sessions continued daily for 2 weeks. Traditional behavioral and computational reinforcement learning-derived measures were examined. RESULTS: Results showed that ketamine had acute effects 1-h post-injection, including a significant decrease in the value of the punishment learning rate. Beyond 1 h, ketamine produced no detectable improvements nor decrements in performance across 2 weeks. CONCLUSION: Overall, the present results suggest that the range of ketamine doses examined do not have long-term positive or negative effects on cognitive flexibility or reward processing in healthy rats as measured by the PRL.


Subject(s)
Depressive Disorder, Major , Ketamine , Rats , Humans , Male , Animals , Ketamine/pharmacology , Depressive Disorder, Major/drug therapy , Reinforcement, Psychology , Reversal Learning , Cognition
16.
Psychoneuroendocrinology ; 160: 106917, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38071877

ABSTRACT

Oxytocin (OT) influences a range of social behaviors by enhancing the salience of social cues and regulating the expression of specific social behaviors (e.g., maternal care versus defensive aggression). We previously showed that stimulating OT receptors in the basolateral amygdala of rats also enhanced the salience of fear conditioned stimuli: relative to rats given vehicle infusions, rats infused with [Thr4,Gly7]-oxytocin (TGOT), a selective OT receptor agonist, showed greater discrimination between a cue predictive of danger, and one that signaled safety. In the present series of experiments using male rats, the effects of OT receptor activation in the basolateral amygdala on stimulus processing were examined further using conditioning protocols that consist of changes in stimulus-outcome contingencies (i.e., extinction and reversal), and with stimuli paired with aversive (i.e., foot shock) and appetitive (i.e., sucrose) outcomes. It was revealed that the effects of OTR stimulation diverge for aversive and appetitive learning - enhancing the former but not the latter. However, across both types of learning, OTR stimulation enhanced the detection of conditioned stimuli. Overall, these results are consistent with an emerging view of OT's effects on stimulus salience; facilitating the detection of meaningful stimuli while reducing responding to those that are irrelevant.


Subject(s)
Basolateral Nuclear Complex , Rats , Male , Animals , Basolateral Nuclear Complex/metabolism , Receptors, Oxytocin/metabolism , Oxytocin/pharmacology , Oxytocin/metabolism , Reversal Learning , Fear/physiology
17.
Neuropharmacology ; 244: 109801, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38040286

ABSTRACT

BACKGROUND: The interplay between environmental stress and genetic factors is thought to play an important role in the pathogenesis and maintenance of obsessive-compulsive disorder (OCD). However, the relative contribution of these causative antecedents in the manifestation of cognitive inflexibility-a phenotype often seen in obsessive-compulsive (OC)- spectrum disorders-is not fully understood. METHOD: In this study, we treated mice with 50 mg/L corticosterone (CORT, a glucocorticoid stress hormone) in their drinking water during adolescence. In adulthood, we assessed anxiety-like behaviour and locomotor activity; along with operant-based discrimination and reversal learning. RU-24969, a selective serotonin receptor 5-HT1A/1B receptor agonist, was used as an acute pharmacological model of OC-like behaviour. RU-24969 (5 mg/kg) was administered prior to each reversal learning testing session. RESULTS: We found that acute treatment with 5 mg/kg RU-24969 induced stereotyped hyperlocomotion in vehicle- and CORT-treated mice. Furthermore, pre-treatment with CORT in adolescence produced subtle anxiety-like behaviour in adult mice, and also resulted in an impairment to late-stage discrimination learning and alterations to reversal learning. Finally, acute treatment with 5 mg/kg RU-24969 caused an impairment to early-stage reversal learning. CONCLUSION: Whilst we revealed dissociable detrimental effects of adolescent CORT treatment and acute 5-HT1A/1B receptor agonism on discrimination and reversal learning, respectively, we did not find evidence of additive deleterious effects of these two treatments. We therefore suggest that while disrupted serotonergic signalling is likely to be involved in the cognitive phenotype of OC-spectrum disorders, distinct neuropathological pathways may be at play in mediating the role of stress as an antecedent in OCD and related illnesses.


Subject(s)
Obsessive-Compulsive Disorder , Serotonin , Mice , Animals , Serotonin/pharmacology , Serotonin Receptor Agonists/therapeutic use , Obsessive-Compulsive Disorder/drug therapy , Selective Serotonin Reuptake Inhibitors , Reversal Learning
18.
Neuropsychopharmacology ; 49(3): 600-608, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37914893

ABSTRACT

Serotonin is critical for adapting behavior flexibly to meet changing environmental demands. Cognitive flexibility is important for successful attainment of goals, as well as for social interactions, and is frequently impaired in neuropsychiatric disorders, including obsessive-compulsive disorder. However, a unifying mechanistic framework accounting for the role of serotonin in behavioral flexibility has remained elusive. Here, we demonstrate common effects of manipulating serotonin function across two species (rats and humans) on latent processes supporting choice behavior during probabilistic reversal learning, using computational modelling. The findings support a role of serotonin in behavioral flexibility and plasticity, indicated, respectively, by increases or decreases in choice repetition ('stickiness') or reinforcement learning rates following manipulations intended to increase or decrease serotonin function. More specifically, the rate at which expected value increased following reward and decreased following punishment (reward and punishment 'learning rates') was greatest after sub-chronic administration of the selective serotonin reuptake inhibitor (SSRI) citalopram (5 mg/kg for 7 days followed by 10 mg/kg twice a day for 5 days) in rats. Conversely, humans given a single dose of an SSRI (20 mg escitalopram), which can decrease post-synaptic serotonin signalling, and rats that received the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), which destroys forebrain serotonergic neurons, exhibited decreased reward learning rates. A basic perseverative tendency ('stickiness'), or choice repetition irrespective of the outcome produced, was likewise increased in rats after the 12-day SSRI regimen and decreased after single dose SSRI in humans and 5,7-DHT in rats. These common effects of serotonergic manipulations on rats and humans-identified via computational modelling-suggest an evolutionarily conserved role for serotonin in plasticity and behavioral flexibility and have clinical relevance transdiagnostically for neuropsychiatric disorders.


Subject(s)
Citalopram , Serotonin , Humans , Rats , Animals , Serotonin/physiology , Citalopram/pharmacology , Selective Serotonin Reuptake Inhibitors/pharmacology , Reinforcement, Psychology , Reversal Learning/physiology
19.
J Neurosci ; 44(2)2024 Jan 10.
Article in English | MEDLINE | ID: mdl-37968116

ABSTRACT

Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including the highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, the unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory designer receptors exclusively activated by designer drugs targeting projection neurons in these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We assessed initial and pre-/post-reversal changes in performance to measure learning and adjustments to reversals, respectively. We found that inhibition of the ventrolateral orbitofrontal cortex (vlOFC), but not BLA, eliminated adjustments to stimulus-based reversals. Inhibition of BLA, but not vlOFC, selectively impaired action-based probabilistic reversal learning, leaving deterministic reversal learning intact. vlOFC exhibited a sex-dependent role in early adjustment to action-based reversals, but not in overall learning. These results reveal dissociable roles for BLA and vlOFC in flexible learning and highlight a more crucial role for BLA in learning meaningful changes in the reward environment.


Subject(s)
Basolateral Nuclear Complex , Rats , Male , Female , Animals , Uncertainty , Basolateral Nuclear Complex/physiology , Rats, Long-Evans , Prefrontal Cortex/physiology , Reversal Learning/physiology
20.
Sportis (A Coruña) ; 10(1): 14-31, 2024. ilus, graf
Article in Spanish | IBECS | ID: ibc-229133

ABSTRACT

Virtual education has evolved significantly, driven by the integration of Information and Communication Technology (ICT) resources, particularly during the COVID-19 pandemic. Health Sciences, with their practical components, present unique challenges in virtual education, including maintaining student engagement. This study aimed to compare the effectiveness of the flipped learning methodology with and without in-class content reinforcement in a virtual classroom for previously assimilated materials within Health Sciences. The study involved students in a Kinesiology program using the Blackboard Learn platform. Two groups were established: one completing a questionnaire at the beginning of the virtual class (FLI group) and the other at the end following a content reinforcement session (FLI+TRA group). While no statistically significant score differences were found between the two groups, the FLI+TRA group showed higher pass rates and improved average scores, indicating practical benefits. These results suggest that combining flipped learning with traditional in-class instruction can enhance content assimilation in virtual education, fostering increased student engagement and participation. However, further research is needed to explore the full implications and adaptability of this approach. In conclusion, this study highlights the potential of the FLI+TRA approach to improve learning outcomes in complex subjects like Epistemology and Research Methodology within Health Sciences. As virtual education continues to evolve, educators should consider this hybrid teaching model as a valuable tool to provide a more holistic and effective learning experience (AU)


La educación virtual ha evolucionado significativamente, impulsada por la integración de recursos de Tecnologías de la Información y Comunicación (TIC), especialmente durante la pandemia de COVID-19. Las Ciencias de la Salud, con sus componentes prácticos, presentan desafíos únicos en la educación virtual, incluida la retención del interés de los estudiantes. Este estudio tuvo como objetivo comparar la efectividad de la metodología de aprendizaje invertido (flipped learning) con y sin refuerzo de contenido en clase en un aula virtual para materiales previamente asimilados en Ciencias de la Salud. El estudio involucró a estudiantes de un programa de Kinesiología utilizando la plataforma Blackboard Learn. Se establecieron dos grupos: uno completando un cuestionario al comienzo de la clase virtual (grupo FLI) y otro al final después de una sesión de refuerzo de contenido en clase (grupo FLI+TRA). Aunque no se encontraron diferencias estadísticamente significativas en las puntuaciones entre los dos grupos, el grupo FLI+TRA mostró tasas de aprobación más altas y puntajes promedio mejorados, lo que indica beneficios prácticos. Estos resultados sugieren que la combinación de aprendizaje invertido con instrucción tradicional en clase puede mejorar la asimilación de contenido en la educación virtual, fomentando un mayor compromiso y participación de los estudiantes. Sin embargo, se necesita más investigación para explorar las implicaciones y la adaptabilidad completas de este enfoque. En conclusión, este estudio resalta el potencial del enfoque FLI+TRA para mejorar los resultados de aprendizaje en materias complejas como Epistemología y Metodología de Investigación en Ciencias de la Salud. A medida que la educación virtual continúa evolucionando, los educadores deben considerar este modelo de enseñanza híbrido como una herramienta valiosa para proporcionar una experiencia de aprendizaje más holística y efectiva (AU)


Subject(s)
Humans , Reversal Learning , Health Sciences/education , Kinesiology, Applied/education , Virtual Reality , Education, Distance/methods
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