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The brain responds to experience through modulation of synaptic transmission, that is synaptic plasticity. An increase in the strength of synaptic transmission is manifested as long-term potentiation (LTP), while a decrease in the strength of synaptic transmission is expressed as long-term depression (LTD). Most of the studies of synaptic plasticity have been carried out by induction via electrophysiological stimulation. It is largely unknown in which behavioural tasks such synaptic plasticity occurs. Moreover, some stimuli can induce both LTP and LTD, thus making it difficult to separately study the different forms of synaptic plasticity. Two studies have shown that an aversive memory task – inhibitory avoidance learning and contextual fear conditioning – physiologically and selectively induce LTP and an LTP-like molecular change, respectively, in the hippocampus in vivo. Here, we show that a non-aversive behavioural task – exploration of new space – physiologically and selectively elicits a biochemical change in the hippocampus that is a hallmark of LTP. Specifically, we found that exploration of new space induces an increase in the phosphorylation of GluA1(Ser831), without affecting the phosphorylation of GluA1(Ser845), which are biomarkers of early-LTP and not NMDAR-mediated LTD. We also show that exploration of new space engenders the phosphorylation of the translational regulator S6K and the expression of Arc, which are features of electrophysiologically-induced late-LTP in the hippocampus. Therefore, our results show that exploration of new space is a novel non-aversive behavioural paradigm that elicits molecular changes in vivo that are analogous to those occurring during early- and late-LTP, but not during NMDAR-mediated LTD. [ABSTRACT FROM AUTHOR]

The following paper describes a steady-state model of concurrent choice, termed the active time model (ATM). ATM is derived from maximization principles and is characterized by a semi-Markov process. The model proposes that the controlling stimulus in concurrent variable-interval (VI) VI schedules of reinforcement is the time interval since the most recent response, termed here "the active interresponse time" or simply "active time." In the model after a response is generated, it is categorized by a function that relates active times to switch/stay probabilities. In the paper the output of ATM is compared with predictions made by three other models of operant conditioning: melioration, a version of scalar expectancy theory (SET), and momentary maximization. Data sets considered include preferences in multiple-concurrent VI VI schedules, molecular choice patterns, correlations between switching and perseveration, and molar choice proportions. It is shown that ATM can account for all of these data sets, while the other models produce more limited fits. However, rather than argue that ATM is the singular model for concurrent VI VI choice, a consideration of its concept space leads to the conclusion that operant choice is multiply-determined, and that an adaptive viewpoint–one that considers experimental procedures both as selecting mechanisms for animal choice as well as tests of the controlling variables of that choice–is warranted. [ABSTRACT FROM AUTHOR]

Highly palatable food triggers behavioral responses including strong motivation. These effects involve the reward system and dopamine neurons, which modulate neurons in the nucleus accumbens (NAc). The molecular mechanisms underlying the long-lasting effects of highly palatable food on feeding behavior are poorly understood. We studied the effects of 2-week operant conditioning of mice with standard or isocaloric highly palatable food. We investigated the behavioral responses and dendritic spine modifications in the NAc. We compared the translating messenger RNA in NAc neurons identified by the type of dopamine receptors they express, depending on the kind of food and training. We tested the consequences of invalidation of an abundant downregulated gene, Ncdn. Operant conditioning for highly palatable food increased motivation for food even in well-fed mice. In wild-type mice, free choice between regular and highly palatable food increased weight compared with access to regular food only. Highly palatable food increased spine density in the NAc. In animals trained for highly palatable food, translating messenger RNAs were modified in NAc neurons expressing dopamine D 2 receptors, mostly corresponding to striatal projection neurons, but not in neurons expressing D 1 receptors. Knockout of Ncdn , an abundant downregulated gene, opposed the conditioning-induced changes in satiety-sensitive feeding behavior and apparent motivation for highly palatable food, suggesting that downregulation may be a compensatory mechanism. Our results emphasize the importance of messenger RNA alterations in D 2 striatal projection neurons in the NAc in the behavioral consequences of highly palatable food conditioning and suggest a modulatory contribution of Ncdn downregulation. [ABSTRACT FROM AUTHOR]

• Dopamine release in dorsomedial striatum tracks learning, movement and motivation. • Bilateral dopamine release at the time of reward reflects the current action value. • Bilateral dopamine release at the time of reward reflects the prediction error. • Dopamine release becomes increasingly lateralized during goal-directed learning. • Dopamine laterization reflects the strength of the action-outcome association. Evidence suggests that dopamine activity provides a US-related prediction error for Pavlovian conditioning and the reinforcement signal supporting the acquisition of habits. However, its role in goal-directed action is less clear. There are currently few studies that have assessed dopamine release as animals acquire and perform self-paced instrumental actions. Here we briefly review the literature documenting the psychological, behavioral and neural bases of goal-directed actions in rats and mice, before turning to describe recent studies investigating the role of dopamine in instrumental learning and performance. Plasticity in dorsomedial striatum, a central node in the network supporting goal-directed action, clearly requires dopamine release, the timing of which, relative to cortical and thalamic inputs, determines the degree and form of that plasticity. Beyond this, bilateral release appears to reflect reward prediction errors as animals experience the consequences of an action. Such signals feedforward to update the value of the specific action associated with that outcome during subsequent performance, with dopamine release at the time of action reflecting the updated predicted action value. More recently, evidence has also emerged for a hemispherically lateralised signal associated with the action; dopamine release is greater in the hemisphere contralateral to the spatial target of the action. This effect emerges over the course of acquisition and appears to reflect the strength of the action-outcome association. Thus, during goal-directed action, dopamine release signals the action, the outcome and their association to shape the learning and performance processes necessary to support this form of behavioral control. [ABSTRACT FROM AUTHOR]

We are studying the mechanisms of H‐reflex operant conditioning, a simple form of learning. Modelling studies in the literature and our previous data suggested that changes in the axon initial segment (AIS) might contribute. To explore this, we used blinded quantitative histological and immunohistochemical methods to study in adult rats the impact of H‐reflex conditioning on the AIS of the spinal motoneuron that produces the reflex. Successful, but not unsuccessful, H‐reflex up‐conditioning was associated with greater AIS length and distance from soma; greater length correlated with greater H‐reflex increase. Modelling studies in the literature suggest that these increases may increase motoneuron excitability, supporting the hypothesis that they may contribute to H‐reflex increase. Up‐conditioning did not affect AIS ankyrin G (AnkG) immunoreactivity (IR), p‐p38 protein kinase IR, or GABAergic terminals. Successful, but not unsuccessful, H‐reflex down‐conditioning was associated with more GABAergic terminals on the AIS, weaker AnkG‐IR, and stronger p‐p38‐IR. More GABAergic terminals and weaker AnkG‐IR correlated with greater H‐reflex decrease. These changes might potentially contribute to the positive shift in motoneuron firing threshold underlying H‐reflex decrease; they are consistent with modelling suggesting that sodium channel change may be responsible. H‐reflex down‐conditioning did not affect AIS dimensions. This evidence that AIS plasticity is associated with and might contribute to H‐reflex conditioning adds to evidence that motor learning involves both spinal and brain plasticity, and both neuronal and synaptic plasticity. AIS properties of spinal motoneurons are likely to reflect the combined influence of all the motor skills that share these motoneurons. Key points: Neuronal action potentials normally begin in the axon initial segment (AIS). AIS plasticity affects neuronal excitability in development and disease. Whether it does so in learning is unknown.Operant conditioning of a spinal reflex, a simple learning model, changes the rat spinal motoneuron AIS. Successful, but not unsuccessful, H‐reflex up‐conditioning is associated with greater AIS length and distance from soma. Successful, but not unsuccessful, down‐conditioning is associated with more AIS GABAergic terminals, less ankyrin G, and more p‐p38 protein kinase.The associations between AIS plasticity and successful H‐reflex conditioning are consistent with those between AIS plasticity and functional changes in development and disease, and with those predicted by modelling studies in the literature.Motor learning changes neurons and synapses in spinal cord and brain. Because spinal motoneurons are the final common pathway for behaviour, their AIS properties probably reflect the combined impact of all the behaviours that use these motoneurons. [ABSTRACT FROM AUTHOR]

This article is the author’s response to a commentary on their original article, “Methodological integrity assessment in the mobile paradigm literature: A lesson for understanding opportunistic use of researcher degrees of freedom in psychology”. Here Sen and Gredebäck respond to each aspect of the commentary on the topics of null findings, the dependency between learning criteria and memory, the utilization of simulations in mobile paradigm research, and memory development in early infancy.

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. [ABSTRACT FROM AUTHOR]

Deciding on a course of action requires both an accurate estimation of option values and the right amount of effort invested in deliberation to reach sufficient confidence in the final choice. In a previous study, we have provided evidence, across a series of judgment and choice tasks, for a dissociation between the ventromedial prefrontal cortex (vmPFC), which would represent option values, and the dorsomedial prefrontal cortex (dmPFC), which would represent the duration of deliberation. Here, we first replicate this dissociation and extend it to the case of an instrumental learning task, in which 24 human volunteers (13 women) choose between options associated with probabilistic gains and losses. According to fMRI data recorded during decision-making, vmPFC activity reflects the sum of option values generated by a reinforcement learning model and dmPFC activity the deliberation time. To further generalize the role of the dmPFC in mobilizing effort, we then analyze fMRI data recorded in the same participants while they prepare to perform motor and cognitive tasks (squeezing a handgrip or making numerical comparisons) to maximize gains or minimize losses. In both cases, dmPFC activity is associated with the output of an effort regulation model, and not with response time. Taken together, these results strengthen a general theory of behavioral control that implicates the vmPFC in the estimation of option values and the dmPFC in the energization of relevant motor and cognitive processes. [ABSTRACT FROM AUTHOR]

Motivation to seek social interactions is inherent to all social species. For instance, even with risk of disease transmission in a recent pandemic, humans sought out frequent in-person social interactions. In other social animals, socialization can be prioritized even over water or food consumption. Zebra finches, Taeniopygia guttata , are highly gregarious songbirds widely used in behavioural and physiological research. Songbirds, like humans, are vocal learners during development, which rely on intense auditory learning. Aside from supporting song learning, auditory learning further supports individual identification, mate choice and outcome associations in songbirds. To study auditory learning in a laboratory setting, studies often employ operant paradigms with food restriction and reinforcement and require complete social isolation, which can result in stress and other unintended physiological consequences for social species. Thus, in this work, we designed an operant behavioural method leveraging the sociality of zebra finches for goal-directed behaviours. Our approach relies on visual social reinforcement, without depriving the animals of food or social contact. Using this task, we found that visual social reinforcement was a strong motivational drive for operant behaviour. Motivation was sensitive to familiarity towards the stimulus animal and higher when engaging with a familiar versus a novel individual. We further show that this tool can be used to assess auditory discrimination learning using either songs or synthetic pure tones as stimuli. As birds gained experience in the task, they developed a strategy to maximize reward acquisition in spite of receiving more punishment, i.e. liberal response bias. Our operant paradigm provides an alternative to tasks using food reinforcement and could be applied to a variety of highly social species, such as rodents and nonhuman primates. • We used a novel social reward-based operant task for zebra finches. • Birds were more motivated to obtain access to familiar over novel conspecifics. • Social motivation reinforced auditory discrimination learning in a Go/No-go task. • Birds with more experience in the Go/No-go task developed liberal response bias. [ABSTRACT FROM AUTHOR]

Associative learning and memory, i.e., learning and remembering the associations between environmental stimuli, self-generated actions, and outcomes such as rewards or punishments, are critical for the well-being of animals. Hence, the neural mechanisms underlying these processes are extensively studied using behavioral tasks in laboratory animals. Traditionally, these tasks have been controlled using commercial hardware and software, which limits scalability and accessibility due to their cost. More recently, due to the revolution in microcontrollers or microcomputers, several general-purpose and open-source solutions have been advanced for controlling neuroscientific behavioral tasks. While these solutions have great strength due to their flexibility and general-purpose nature, for the same reasons, they suffer from some disadvantages including the need for considerable programming expertise, limited online visualization, or slower than optimal response latencies for any specific task. Here, to mitigate these concerns, we present an open-source behavior controller for associative learning and memory (B-CALM). B-CALM provides an integrated suite that can control a host of associative learning and memory behaviors. As proof of principle for its applicability, we show data from head-fixed mice learning Pavlovian conditioning, operant conditioning, discrimination learning, as well as a timing task and a choice task. These can be run directly from a user-friendly graphical user interface (GUI) written in MATLAB that controls many independently running Arduino Mega microcontrollers in parallel (one per behavior box). In sum, B-CALM will enable researchers to execute a wide variety of associative learning and memory tasks in a scalable, accurate, and user-friendly manner. [ABSTRACT FROM AUTHOR]

Obsessive-compulsive disorder (OCD), a highly prevalent and debilitating disorder, is incompletely understood in terms of underpinning behavioural, psychological, and neural mechanisms. This is attributable to high symptomatic heterogeneity; cardinal features comprise obsessions and compulsions, including clinical subcategories. While obsessive and intrusive thoughts are arguably unique to humans, dysfunctional behaviours analogous to those seen in clinical OCD have been examined in nonhuman animals. Genetic, ethological, pharmacological, and neurobehavioural approaches all contribute to understanding the emergence and persistence of compulsive behaviour. One behaviour of particular interest is maladaptive checking, whereby human patients excessively perform checking rituals despite these serving no purpose. Dysfunctional and excessive checking is the most common symptom associated with OCD and can be readily operationalised in rodents. This review considers animal models of OCD, the neural circuitries associated with impairments in habit-based and goal-directed behaviour, and how these may link to the compulsions observed in OCD. We further review the Observing Response Task (ORT), an appetitive instrumental learning procedure that distinguishes between functional and dysfunctional checking, with translational application in humans and rodents. By shedding light on the psychological and neural bases of compulsive-like checking, the ORT has potential to offer translational insights into the underlying mechanisms of OCD, in addition to being a platform for testing psychological and neurochemical treatment approaches. [ABSTRACT FROM AUTHOR]

Three experiments explored whether weakening temporal contiguity between auditory cues and an aversive outcome attenuated cue competition in an avoidance learning task with human participants. Overall, with strong temporal contiguity between auditory cues and the outcome during training (the offset of the predictive auditory signals concurred with the onset of the outcome), the target cue trained as part of a compound yielded less avoidance behaviour than the control cue trained alone, an instance of overshadowing. However, weakening temporal contiguity during training (inserting a 5-s trace) attenuated overshadowing, resulting in similar avoidance behaviour in response to the control and target cues. These results provide evidence that, as predicted by a recent modification of Pearce's configural theory, temporal contiguity is critical for determining cue competition. [ABSTRACT FROM AUTHOR]

Evaluative Conditioning (EC) refers to changes in our liking or disliking of a stimulus due to its pairing with other positive or negative stimuli. In addition to stimulus-based mechanisms, recent research has shown that action-based mechanisms can also lead to EC effects. Research, based on action control theories, has shown that pairing a positive or negative action with a neutral stimulus results in EC effects (Stimulus-Response binding). Similarly, research studies using Operant Conditioning (OC) approaches have also observed EC effects. The aim of the present study is to directly compare EC effects elicited by two different response-based approaches – S-R bindings and OC. To this end, participants were randomly assigned to an S-R binding procedure and an OC procedure. EC effects were measured in conditions and compared. Implications for EC theory are discussed. [ABSTRACT FROM AUTHOR]

Operant conditioning of neural activation has been researched for decades in humans and animals. Many theories suggest two parallel learning processes, implicit and explicit. The degree to which feedback affects these processes individually remains to be fully understood and may contribute to a large percentage of non-learners. Our goal is to determine the explicit decision-making processes in response to feedback representing an operant conditioning environment. We developed a simulated operant conditioning environment based on a feedback model of spinal reflex excitability, one of the simplest forms of neural operant conditioning. We isolated the perception of the feedback signal from self-regulation of an explicit unskilled visuomotor task, enabling us to quantitatively examine feedback strategy. Our hypothesis was that feedback type, biological variability, and reward threshold affect operant conditioning performance and operant strategy. Healthy individuals (N = 41) were instructed to play a web application game using keyboard inputs to rotate a virtual knob representative of an operant strategy. The goal was to align the knob with a hidden target. Participants were asked to "down-condition" the amplitude of the virtual feedback signal, which was achieved by placing the knob as close as possible to the hidden target. We varied feedback type (knowledge of performance, knowledge of results), biological variability (low, high), and reward threshold (easy, moderate, difficult) in a factorial design. Parameters were extracted from real operant conditioning data. Our main outcomes were the feedback signal amplitude (performance) and the mean change in dial position (operant strategy). We observed that performance was modulated by variability, while operant strategy was modulated by feedback type. These results show complex relations between fundamental feedback parameters and provide the principles for optimizing neural operant conditioning for non-responders. [ABSTRACT FROM AUTHOR]

Phasic dopamine activity is believed to both encode reward‐prediction errors (RPEs) and to cause the adaptations that these errors engender. If so, a rat working for optogenetic stimulation of dopamine neurons will repeatedly update its policy and/or action values, thus iteratively increasing its work rate. Here, we challenge this view by demonstrating stable, non‐maximal work rates in the face of repeated optogenetic stimulation of midbrain dopamine neurons. Furthermore, we show that rats learn to discriminate between world states distinguished only by their history of dopamine activation. Comparison of these results to reinforcement learning simulations suggests that the induced dopamine transients acted more as rewards than RPEs. However, pursuit of dopaminergic stimulation drifted upwards over a time scale of days and weeks, despite its stability within trials. To reconcile the results with prior findings, we consider multiple roles for dopamine signalling. [ABSTRACT FROM AUTHOR]

Recently, there has been a renewed interest in avoidance behavior, and its applicability to clinical conditions such as anxiety, posttraumatic stress disorder (PTSD) and addiction. In a computer-based avoidance task for humans, participants control an on-screen spaceship, shoot at enemy targets (appetitive cue) to gain points, and learn to respond to an on-screen warning signal (WS) by entering safe "hiding" areas to escape/avoid an aversive event (point loss and on-screen explosion) paired with an on-screen aversive cue (bomb). Prior research on active avoidance in rodents suggests that avoidance learning is facilitated if the response also terminates the WS. Here, we adapted the computer-based task to investigate this idea in healthy humans. Two hundred and twenty-two young adults completed one of three conditions of the task: a non-contingent condition, where hiding caused omission/avoidance of the aversive event but did not terminate the WS; a fully-contingent condition, where hiding also caused omission/termination of all on-screen appetitive and aversive cues as well as terminating the WS; and a partially-contingent condition where hiding caused omission of the appetitive and aversive cues, but did not affect the WS. Both contingency manipulations decreased escape/avoidance behavior, as compared to the non-contingent condition where the WS and other cues are not affected by the avoidance behavior. This study has implications for the basic understanding of the mechanisms that affect avoidance behavior in humans. [ABSTRACT FROM AUTHOR]

This article presents a commentary on Sen and Gredebäck’s “Methodological integrity assessment in the mobile paradigm literature: A lesson for understanding opportunistic use of researcher degrees of freedom in psychology” presented in this issue. The authors discuss the operant mobile paradigm in infant memory research as well as degrees of freedom and an evaluation of the paper’s simulation analyses.

The mobile paradigm has played a fundamental role in memory development research. One key characteristic of the mobile paradigm literature is that across decades, researchers have faithfully followed a particular methodological protocol with its own unique definitions of learning and memory. To investigate the extent to which these methodological choices affected the results, the literature (77 publications and 505 statistical tests) was evaluated for four frequently encountered research biases. The results suggested that research using the paradigm was conducted with scientific rigor. However, methodological choices along with unique operational definitions of learning and memory accounted for more than half of the findings. Thus, the literature has been contaminated by methodological artifacts due to the opportunistic use of researcher degrees of freedom. [ABSTRACT FROM AUTHOR]

Both non‐rapid eye movement (NonREM) sleep and rapid eye movement (REM) sleep, as well as sleep spindle and ripple oscillations, are important for memory formation. Through cortical EEG recordings of prefrontal cortex and hippocampus during and after an inhibitory avoidance task, we analysed the dynamic changes in the amounts of sleep, spindle and ripple oscillations related to memory formation. The total amount of NonREM sleep was reduced during the first hour after learning. Moreover, significant decrease of the total spindle and ripple counts was observed at the first hour after learning as well. In addition, foot shock alone, with no associated learning, produced little effect on the dynamics of sleep oscillations, indicating that the learning experience is necessary for these changes to occur. [ABSTRACT FROM AUTHOR]

An organism's ability to learn characteristics of its environment in the presence or absence of certain stimuli is a vital aspect of its survival. However, the level at which certain species can learn is thought to vary along the phylogenic tree. We assess free living freshwater flatworms (Dugesia tigrina) ability to learn via classical and operant conditioning. Flatworms' ability to learn via classical and operant conditioning was assessed using an electric shock and red light inside an arena. A stronger curling response after training flatworms to associate a red light with a negative stimulus indicates flatworms possess the ability to learn through classical conditioning. Flatworms also actively avoided red light after it was paired with negative stimulus, indicating the capacity for operant conditioning. Despite a primitive nervous system, wild-caught freshwater flatworms exhibit two fundamental forms of learning which could facilitate adaptive foraging and predator avoidance behaviors. In addition, these results add clarity to the debate surrounding the learning capacity within Platyhelminthes and further our understanding of learning among primitive animals. [ABSTRACT FROM AUTHOR]

The hippocampus has been implicated in temporal learning. Plasticity within the hippocampus requires NMDA receptor‐dependent glutamatergic neurotransmission. We tested the prediction that hippocampal NMDA receptors are required for learning about time by testing mice that lack postembryonal NMDARs in the CA1 and dentate gyrus (DG) hippocampal subfields on three different appetitive temporal learning procedures. The conditional knockout mice (Grin1ΔDCA1) showed normal sensitivity to cue duration, responding at a higher level to a short duration cue than compared to a long duration cue. Knockout mice also showed normal precision and accuracy of response timing in the peak procedure in which reinforcement occurred after 10 s delay within a 30 s cue presentation. Mice were tested on the matching of response rates to reinforcement rates on instrumental conditioning with two levers reinforced on a concurrent variable interval schedule. Pressing on one lever was reinforced at a higher rate than the other lever. Grin1ΔDGCA1 mice showed normal sensitivity to the relative reinforcement rates of the levers. In contrast to the lack of effect of hippocampal NMDAR deletion on measures of temporal sensitivity, Grin1ΔDGCA1 mice showed increased baseline measures of magazine activity and lever pressing. Furthermore, reversal learning was enhanced when the reward contingencies were switched in the lever pressing task, but this was true only for mice trained with a large difference between relative reinforcement rates between the levers. The results failed to demonstrate a role for NMDARs in excitatory CA1 and DG neurons in learning about temporal information. [ABSTRACT FROM AUTHOR]

Simple Summary: The idea that invertebrates feel pain is often dismissed because of claims that their responses to noxious stimuli are simply reflexes. Reflexes do not require higher-order processing, but that is required for pain experience. One way to test this claim is to ask if animals only respond to the noxious stimulus or if that response can be influenced by other motivations. Here, we report that shore crabs that enter a dark shelter from a light area and receive a shock are subsequently less likely to use that shelter if the light level is low and the shock level high. They trade their requirement to avoid bright light for the avoidance of the noxious shock. They learn to avoid the shelter and show signs of anxiety when deciding to enter the shelter to escape the light. These observations demonstrate that the responses to shock are not reflexes but are decisions that should improve the outcome better than a reflex alone. This balancing of needs is a key expectation of pain, and the results are consistent with the idea that crabs feel pain. The suggestion that decapod crustaceans might experience pain has been dismissed by some authors who claim decapods only respond to noxious stimuli by nociceptive reflexes. Because reflexes do not require complex neuronal processing, but pain does, demonstrating reflex responses to noxious stimuli would not support the case for pain. Here, we report an experiment in which shore crabs are repeatedly placed in a light area (20 trials), but the animals can avoid the light by moving to a dark shelter. However, some crabs received an electric shock of 6 or 12 volts each time they entered the shelter. Those receiving either level of shock swiftly reduced their use of shelters and remained in the light. However, the magnitude of shelter avoidance was influenced by the brightness of the arena and the intensity of the shock. Shelter use was subsequently reduced to a greater extent if the shock level was high and the light intensity low. That is, crabs traded their avoidance of shock for their avoidance of bright light. Further, these animals showed avoidance learning and demonstrated activities suggesting anxiety, such as contact with the tank wall in the light area and increased latency to enter shelters when making the decision to enter the shelter if they had received shock in earlier trials. These results fulfil three key behavioural criteria for pain and, thus, are consistent with the idea that decapods can experience pain. [ABSTRACT FROM AUTHOR]

Cisplatin, a chemotherapy drug containing platinum, is considered a neurotoxic agent. On the other hand, crocin, the primary component of saffron, possesses neuroprotective and antioxidant properties. In this study, 28 healthy adult male Wistar rats weighing 200–250 g were used (6–7 weeks old). Rats were divided into a control group (Ctr), a crocin group (Cro), a cisplatin group (Cis), and a crocin with cisplatin group (Cro + Cis). Rotarod, open field, and shuttle box tests were performed to assess balance, explorative behavior, and avoidance memory. After behavioral testing, the hippocampus was extracted to analyze oxidative stress parameters such as GPx (glutathione peroxidase), SOD (superoxide dismutase), CAT (catalase), and MDA (malondialdehyde) activity. Shuttle box, rotarod, and open field results showed that crocin can substantially mitigate the deleterious effects of cisplatin on avoidance memory, explorative behavior, motor coordination, and balance. Crocin was also able to effectively avoid the negative effects of cisplatin on MDA, GPx, and CAT during the assessment of oxidative indicators, while the beneficial effect of crocin on cisplatin was not statistically significant in terms of SOD level. In conclusion, since free radicals produced by cisplatin are a contributing factor to memory loss and movement disorders, crocin, owing to its antioxidant properties, improved passive avoidance learning as well as motor activity. [ABSTRACT FROM AUTHOR]

Monoterpenes are a large class of naturally occurring fragrant molecules. These chemicals are commonly used in olfactory studies to survey neural activity and probe the behavioral limits of odor discrimination. Monoterpenes (typically in the form of essential oils) have been used for centuries for therapeutic purposes and have pivotal roles in various biological and medical applications. Despite their importance for multiple lines of research using rodent models and the role of the olfactory system in detecting these volatile chemicals, the murine sensitivity to monoterpenes remains mostly unexplored. We assayed the ability of C57BL/6J mice to detect nine different monoterpenes (the acyclic monoterpenes: geraniol, citral, and linalool; the monocyclic monoterpenes: r-limonene, s-limonene, and γ-terpinene; and the bicyclic monoterpenes: eucalyptol, α-pinene, and β-pinene) using a head-fixed Go / No-Go operant conditioning assay. We found that mice can reliably detect monoterpene concentrations in the low parts per billion (ppb) range. Specifically, mice were most sensitive to geraniol (threshold: 0.7 ppb) and least sensitive to γ-terpinene (threshold: 18.1 ppb). These estimations of sensitivity serve to set the lower limit of relevant monoterpene concentrations for functional experiments in mice. To define an upper limit, we estimated the maximum concentrations that a mouse may experience in nature by collating published headspace analyses of monoterpene concentrations emitted from natural sources. We found that natural monoterpenes concentrations typically ranged from ~1 to 1000 ppb. It is our hope that this dataset will help researchers use appropriate monoterpene concentrations for functional studies and provide context for the vapor-phase delivery of these chemicals in studies investigating their biological activity in mice. [ABSTRACT FROM AUTHOR]

Rats are social animals that use ultrasonic vocalizations (USV) in their intraspecific communication. Several types of USV have been previously described, e.g., appetitive 50-kHz USV and aversive short 22-kHz USV. It is not fully understood which aspects of the USV repertoire play important functions during rat ultrasonic exchange. Here, we investigated features of USV emitted by rats trained in operant conditioning, is a form of associative learning between behavior and its consequences, to reinforce the production/emission of 50-kHz USV. Twenty percent of the trained rats learned to vocalize to receive a reward according to an arbitrarily set criterion, i.e., reaching the maximum number of proper responses by the end of each of the last three USV-training sessions, as well as according to a set of measurements independent from the criterion (e.g., shortening of training sessions). Over the training days, these rats also exhibited: an increasing percentage of rewarded 50-kHz calls, lengthening and amplitude-increasing of 50-kHz calls, and decreasing number of short 22-kHz calls. As a result, the potentially learning rats, when compared to non-learning rats, displayed shorter training sessions and different USV structure, i.e. higher call rates, more rewarded 50-kHz calls, longer and louder 50-kHz calls and fewer short 22-kHz calls. Finally, we reviewed the current literature knowledge regarding different lengths of 50-kHz calls in different behavioral contexts, the potential function of short 22-kHz calls as well as speculate that USV may not easily become an operant response due to their primary biological role, i.e., communication of emotional state between conspecifics. [ABSTRACT FROM AUTHOR]

Dopamine D 2 -like agonists show promise as treatments for depression. They are thought to act by enhancing reward learning; however, the mechanisms by which they achieve this are not clear. Reinforcement learning accounts describe 3 distinct candidate mechanisms: increased reward sensitivity, increased inverse decision–temperature, and decreased value decay. As these mechanisms produce equivalent effects on behavior, arbitrating between them requires measurement of how expectations and prediction errors are altered. We characterized the effects of 2 weeks of the D 2 -like agonist pramipexole on reward learning and used functional magnetic resonance imaging measures of expectation and prediction error to assess which of these 3 mechanistic processes were responsible for the behavioral effects. Forty healthy volunteers (50% female) were randomized to 2 weeks of pramipexole (titrated to 1 mg/day) or placebo in a double-blind, between-subject design. Participants completed a probabilistic instrumental learning task before and after the pharmacological intervention, with functional magnetic resonance imaging data collected at the second visit. Asymptotic choice accuracy and a reinforcement learning model were used to assess reward learning. Pramipexole increased choice accuracy in the reward condition with no effect on losses. Participants who received pramipexole had increased blood oxygen level–dependent response in the orbital frontal cortex during the expectation of win trials but decreased blood oxygen level–dependent response to reward prediction errors in the ventromedial prefrontal cortex. This pattern of results indicates that pramipexole enhances choice accuracy by reducing the decay of estimated values during reward learning. The D 2 -like receptor agonist pramipexole enhances reward learning by preserving learned values. This is a plausible mechanism for pramipexole's antidepressant effect. [ABSTRACT FROM AUTHOR]

Separable striatal circuits have unique functions in Pavlovian and instrumental behaviors but how these roles relate to performance of sequences of actions with and without associated cues are less clear. Here, we tested whether dopamine transmission and neural activity more generally in three striatal subdomains are necessary for performance of an action chain leading to reward delivery. Male and female Long‐Evans rats were trained to press a series of three spatially distinct levers to receive reward. We assessed the contribution of neural activity or dopamine transmission within each striatal subdomain when progression through the action sequence was explicitly cued and in the absence of cues. Behavior in both task variations was substantially impacted following microinfusion of the dopamine antagonist, flupenthixol, into nucleus accumbens core (NAc) or dorsomedial striatum (DMS), with impairments in sequence timing and numbers of rewards earned after NAc flupenthixol. In contrast, after pharmacological inactivation to suppress overall activity, there was minimal impact on total rewards earned. Instead, inactivation of both NAc and DMS impaired sequence timing and led to sequence errors in the uncued, but not cued task. There was no impact of dopamine antagonism or reversible inactivation of dorsolateral striatum on either cued or uncued action sequence completion. These results highlight an essential contribution of NAc and DMS dopamine systems in motivational and performance aspects of chains of actions, whether cued or internally generated, as well as the impact of intact NAc and DMS function for correct sequence performance. [ABSTRACT FROM AUTHOR]

Learning and memory are important in everyday life as well as in pathological conditions. The median raphe region (MRR) contributes to memory formation; however, its precise role and the neurotransmitters involved have yet to be elucidated. To address this issue, we stimulated the MRR neurons of mice by chemogenetic technique and studied them in the operant conditioning and active avoidance tests. The virus carrier infected a variety of neuron types including both GABAergic and glutamatergic ones. Behavior was not influenced by stimulation. We hypothesize that the lack of effect was due to opposing effects exerted via GABAergic and glutamatergic neurons. Therefore, next we used VGAT-Cre mice that allowed the specific manipulation of MRR-GABAergic neurons. The stimulation did not affect behavior in the learning phase of the operant conditioning task, but increased reward preference and total responses when operant contingencies were reversed. The enhanced responsiveness might be a proclivity to impulsive behavior. Stimulation facilitated learning in the active avoidance test but did not affect reversal learning in this paradigm. Our findings suggest that MRR-GABAergic neurons are involved in both learning and reversal learning, but the type of learning that is affected depends on the task. [ABSTRACT FROM AUTHOR]

Classic behaviorist and cognitivist approaches to consumer research are based on very different assumptions concerning the nature of the cognitive processes that drive consumption. Classic behaviorist research assumes that the underlying cognitive processes are extremely complex, and the effort to model them is not likely to lead to useful insights. In contrast, classic cognitivist research assumes that the underlying cognitive processes can be precisely captured with simple cognitive models. The current paper highlights the value of a middle ground. This middle ground favors the assumption that while the underlying processes are highly complex, their impact can be approximated with prediction‐oriented cognitive models. The potential of this approach is illustrated with a review of previous research demonstrating how a simple prediction‐oriented model can shed light on four interesting consumption puzzles: Buying and not using, the backfiring of certain safety devices, too much and insufficient checking, and underconsumption and overconsumption. [ABSTRACT FROM AUTHOR]

Our study aimed to investigate the impact of purslane (P. oleracea) and zinc as a therapeutic approach to physiological and biochemical alterations induced by Alzheimer disease (ALZ) in rats. For this purpose, 18 males albino Wistar rats were randomly divided into 4 groups (n=6); healthy rats (Control), untreated Alzheimer rats (Exp ALZ), Alzheimer rats treated with aqueous purslane extract (APE) and Alzheimer rats treated with purslane extract and zinc (PEZn). Various neurological and biological parameters were estimated and brain Histopathology was observed. Results of study showed an alteration in passive avoidance learning (PAL) and a significant increase in AChE activity (P<0.01) and protein, WBC, Monocyte, LYM, platelet and MDA levels and decreasing the GSH levels, GST and SOD activities in Exp ALZ group compared to control. In the other hand, histopathological analysis recorded a deep modification in brain tissues of Alzheimer rats group compared to control. However, the treatment of ALZ rats by APE and zinc ensured a partial amelioration and correction of the previous parameters. We conclude that the use of purslane seems to be the powerful limited of Alzheimer disease development or its complications. [ABSTRACT FROM AUTHOR]

Mood disorders commonly onset during adolescence and young adulthood and are conceptually and empirically related to reinforcement learning abnormalities. However, the nature of abnormalities associated with acute symptom severity versus lifetime diagnosis remains unclear, and prior research has often failed to disentangle working memory from reward processes. The present sample (N = 220) included adolescents and young adults with a lifetime history of unipolar disorders (n = 127), bipolar disorders (n = 28), or no history of psychopathology (n = 62), and varying severity of mood symptoms. Analyses fitted a reinforcement learning and working memory model to an instrumental learning task that varied working memory load, and tested associations between model parameters and diagnoses or current symptoms. Current severity of manic or anhedonic symptoms negatively correlated with task performance. Participants reporting higher severity of current anhedonia, or with lifetime unipolar or bipolar disorders, showed lower reward learning rates. Participants reporting higher severity of current manic symptoms showed faster working memory decay and reduced use of working memory. Computational parameters should be interpreted in the task environment (a deterministic reward learning paradigm), and developmental population. Future work should test replication in other paradigms and populations. Results indicate abnormalities in reinforcement learning processes that either scale with current symptom severity, or correspond with lifetime mood diagnoses. Findings may have implications for understanding reward processing anomalies related to state-like (current symptom) or trait-like (lifetime diagnosis) aspects of mood disorders. • Reward learning anomalies are associated with youth mood symptoms and diagnoses. • Lifetime unipolar disorders predict lower learning rate. • Lifetime bipolar disorders predict poor overall performance. • Acutely elevated anhedonic depression predicts lower learning rate across diagnoses. • Acutely elevated symptoms of mania predict working memory deficits during learning. [ABSTRACT FROM AUTHOR]

The pond snail Lymnaea stagnalis exhibits various forms of associative learning including (1) operant conditioning of aerial respiration where snails are trained not to open their pneumostome in a hypoxic pond water environment using a weak tactile stimulus to their pneumostome as they attempt to open it; and (2) a 24 h-lasting taste-specific learned avoidance known as the Garcia effect utilizing a lipopolysaccharide (LPS) injection just after snails eat a novel food substance (carrot). Typically, lab-inbred snails require two 0.5 h training sessions to form long-term memory (LTM) for operant conditioning of aerial respiration. However, some stressors (e.g., heat shock or predator scent) act as memory enhancers and thus a single 0.5 h training session is sufficient to enhance LTM formation lasting at least 24 h. Here, we found that snails forming a food-aversion LTM following Garcia-effect training exhibited enhanced LTM following operant condition of aerial respiration if trained in the presence of the food substance (carrot) they became averse to. Control experiments led us to conclude that carrot becomes a 'sickness' risk signal and acts as a stressor, sufficient to enhance LTM formation for another conditioning procedure. [ABSTRACT FROM AUTHOR]

Behavioral hearing thresholds and noise localization acuity were determined using a conditioned avoidance/suppression procedure for three Helmeted guineafowl (Numida meleagris). The guineafowl responded to frequencies as low as 2 Hz at 82.5 dB SPL, and as high as 8 kHz at 84.5 dB SPL. At a level of 60 dB SPL, their hearing range spanned 8.12 octaves (24.6 Hz–6.86 kHz). Like most birds, they do not hear sounds above 8 kHz. However, the guineafowl demonstrated good low-frequency hearing (frequencies below 32 Hz), showing thresholds that are more sensitive than both the peafowl and pigeon, both of which hear infrasound. It thus appears that infrasound perception may be more common than previously thought and may have implications for species that inhabit areas with wind energy facilities. The guineafowls' minimum audible angle for a 100-ms broadband noise burst was 13.8 °, at the median for birds and near the mean for mammals. Unlike in mammals, the small sample of bird species and limited representation of lifestyles do not yet allow for meaningful interpretations of the selective pressures or mechanisms that underlie their abilities to locate sound sources. [ABSTRACT FROM AUTHOR]

During social interactions, individuals evaluate relationships with their peers and switch from approach to avoidance, particularly in response to aggressive encounters. A new study in mice investigated the underlying brain mechanisms and identified oxytocin as a key regulator of social avoidance learning. [ABSTRACT FROM AUTHOR]

The greater the reward expectations are, the more different the brain's physiological response will be. Although it is well‐documented that better‐than‐expected outcomes are encoded quantitatively via midbrain dopaminergic (DA) activity, it has been less addressed experimentally whether worse‐than‐expected outcomes are expressed quantitatively as well. We show that larger reward expectations upon unexpected reward omissions are associated with the preceding slower rise and following larger decrease (DA dip) in the DA concentration at the ventral striatum of mice. We set up a lever press task on a fixed ratio (FR) schedule requiring five lever presses as an effort for a food reward (FR5). The mice occasionally checked the food magazine without a reward before completing the task. The percentage of this premature magazine entry (PME) increased as the number of lever presses approached five, showing rising expectations with increasing proximity to task completion, and hence greater reward expectations. Fibre photometry of extracellular DA dynamics in the ventral striatum using a fluorescent protein (genetically encoded GPCR activation‐based DA sensor: GRABDA2m) revealed that the slow increase and fast decrease in DA levels around PMEs were correlated with the PME percentage, demonstrating a monotonic relationship between the DA dip amplitude and degree of expectations. Computational modelling of the lever press task implementing temporal difference errors and state transitions replicated the observed correlation between the PME frequency and DA dip amplitude in the FR5 task. Taken together, these findings indicate that the DA dip amplitude represents the degree of reward expectations monotonically, which may guide behavioural adjustment. [ABSTRACT FROM AUTHOR]

Research suggests that a fast, capacity-limited working memory (WM) system and a slow, incremental reinforcement learning (RL) system jointly contribute to instrumental learning. Thus, situations that strain WM resources alter instrumental learning: under WM loads, learning becomes slow and incremental, the reliance on computationally efficient learning increases, and action selection becomes more random. It is also suggested that Pavlovian learning influences people's behavior during instrumental learning by providing hard-wired instinctive responses including approach to reward predictors and avoidance of punishment predictors. However, it remains unknown how constraints on WM resources affect instrumental learning under Pavlovian influence. Thus, we conducted a functional magnetic resonance imaging (fMRI) study (N = 49) in which participants completed an instrumental learning task with Pavlovian–instrumental conflict (the orthogonalized go/no-go task) both with and without extra WM load. Behavioral and computational modeling analyses revealed that WM load reduced the learning rate and increased random choice, without affecting Pavlovian bias. Model-based fMRI analysis revealed that WM load strengthened RPE signaling in the striatum. Moreover, under WM load, the striatum showed weakened connectivity with the ventromedial and dorsolateral prefrontal cortex when computing reward expectations. These results suggest that the limitation of cognitive resources by WM load promotes slow and incremental learning through the weakened cooperation between WM and RL; such limitation also makes action selection more random, but it does not directly affect the balance between instrumental and Pavlovian systems. Author summary: Among multiple decision-making systems of humans and animals, the Pavlovian system is known for promoting automatic and instinctive behaviors. Understanding the Pavlovian influence on decision-making can offer valuable insights into the mechanism of impulsive and addictive behaviors. Previous studies suggested that prefrontal executive control can be important in regulating the Pavlovian influence. We tested if reducing cognitive resources available for executive control modulates the Pavlovian influence, by adding WM load to an instrumental learning task where Pavlovian influence is beneficial in some conditions but detrimental in others. Contrary to our expectation, constraining cognitive resources with WM load failed to significantly change the contribution of Pavlovian system. Nonetheless, with behavioral analysis and computational modeling, we revealed that WM load promotes slower learning and makes decisions noisier in an instrumental learning task with Pavlovian components. FMRI analysis revealed that WM load strengthens the RPE signaling in striatum upon observing the outcome and weakens the functional connectivity between the prefrontal cortex and the striatum before making a decision. The current study contributes to understanding how cognitive resource constraints alter learning and decision-making under Pavlovian influence as well as the neural mechanisms of those effects. [ABSTRACT FROM AUTHOR]

Deep reinforcement learning (DRL) has proven capable of superhuman performance on many complex tasks. To achieve this success, DRL algorithms train a decision-making agent to select the actions that maximize some long-term performance measure. In many consequential real-world domains, however, optimal performance is not enough to justify an algorithm's use--for example, sometimes a system's robustness, stability, or safety must be rigorously ensured. Thus, methods for verifying DRL systems have emerged. These algorithms can guarantee a system's properties over an infinite set of inputs, but the task is not trivial. DRL relies on deep neural networks (DNNs). DNNs are often referred to as "black boxes" because examining their respective structures does not elucidate their decision-making processes. Moreover, the sequential nature of the problems DRL is used to solve promotes significant scalability challenges. Finally, because DRL environments are often stochastic, verification methods must account for probabilistic behavior. To address these complications, a new subfield has emerged. In this survey, we establish the foundations of DRL and DRL verification, define a taxonomy for DRL verification methods, describe approaches for dealing with stochasticity, characterize considerations related to writing specifications, enumerate common testing tasks/environments, and detail opportunities for future research. [ABSTRACT FROM AUTHOR]

• Link between real-time and subjective regulation success supported the principle of operant conditioning beneath neurofeedback. • Subjective loss of control over eating central to binge-eating disorder decreased after versus before neurofeedback sessions. • Imagination strategies to modulate food-specific prefrontal cortex signals boosted subjective success in binge-eating disorder. Despite the increasing popularity of neurofeedback (NF), aiming at voluntary modulation of dysfunctional prefrontal cortex (PFC) signals in the treatment of binge-eating disorder (BED) and/or overweight, mechanisms remain poorly understood. Based on a randomized-controlled trial offering 12 food-specific real-time functional near-infrared spectroscopy (rtfNIRS)-NF sessions to participants with BED (n = 22), this preregistered study examined (1) online regulation success as predictor for offline regulation success, defined by PFC signals during regulation versus watch, and subjective regulation success, and (2) changes in loss of control (LOC) eating after vs. before and across 12 rtfNIRS-NF-sessions. Higher online regulation success expectedly predicted better subjective, but worse offline regulation success. LOC eating decreased after vs. before, but not over rtfNIRS-NF-sessions, and was not associated with subjective or offline regulation success. The association between online and subjective regulation success confirmed the presumed mechanism of operant conditioning underlying rtfNIRS-NF-learning. The contrary association between online and offline regulation indicated differential PFC involvement upon subtraction of automatic food-specific responses from regulation signals for offline success. Decreased LOC eating after food-specific rtfNIRS-NF-sessions suggested the potential of NF in BED treatment. Results may guide the optimization of future NF studies in larger samples with BED. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a neurodegenerative condition characterized by a gradual onset and progressive deterioration. Recent studies have demonstrated that certain antihyperglycemic drugs can slowdown the progression of AD. Objectives: This study aimed to investigate the effects of sitagliptin (SG) and metformin (MTF) on scopolamine (SCP)-induced learning and memory impairment in both diabetic and non-diabetic mice. Methods: This experimental study was conducted with two subgroups of mice, one diabetic and one non-diabetic. Over a 14-day period, the animals received different doses of SG and MTF in addition to a combination of these two drugs. On the 14th day, SCP was administered, followed by a memory impairment test (passive avoidance learning) conducted 45 minutes later. Subsequently, the animals were sacrificed, and brain samples were collected to measure oxidative stress biomarkers, including malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Results: The obtained findings revealed that intraperitoneal injection of SCP impaired learning and memory function and caused brain oxidative damage in both diabetic and healthy mice. In healthy mice, the administration of high doses of MTF (500 mg/kg) and SG(20 mg/kg), in addition to the combination of these two drugs, significantly reduced memory impairment and oxidative stress. However, in the diabetic groups, only MTF and the combination of MTF with SG could reduce memory impairment and oxidative stress. Conclusions: The authors concluded that these antidiabetic drugs ameliorated oxidative stress by increasing antioxidant capacity and improved scopolamine-induced memory impairment. Furthermore, the combination of these two drugs yielded more favorable results. [ABSTRACT FROM AUTHOR]

Glyphosate, a herbicide marketed as Roundup, is widely used but there are concerns this exposure could impair cognitive function. In the CA1 region of rat hippocampal slices, we investigated whether glyphosate alters synaptic transmission and long-term potentiation (LTP), a cellular model of learning and memory. Our hypothesis is that glyphosate alters neuronal function and impairs LTP induction via activation of pro-inflammatory processes. Roundup depressed excitatory synaptic potentials(EPSPs) in a dose-dependent manner with complete suppression at 2000 mg/L. At concentrations ≤ 20 mg/L Roundup did not affect basal transmission, but 4 mg/L Roundup administered for 30 min inhibited LTP induction. Acute administration of 10–100 μM glyphosate also inhibited LTP induction. Minocycline, an inhibitor of microglial activation, and TAK-242, an inhibitor of toll-like receptor 4 (TLR4), both overcame the inhibitory effects of 100 µM glyphosate. Similarly, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), a different TLR4 antagonist, overcame the inhibitory effects. In addition, ISRIB (integrated stress response inhibitor) and quercetin, an inhibitor of endoplasmic reticulum stress, overcame the inhibitory effects. We also observed that in vivo glyphosate injection (16.9 mg/kg i.p.) impaired one-trial inhibitory avoidance learning. This learning deficit was overcome by TAK-242. These observations indicate that glyphosate can impair cognitive function through pro-inflammatory signaling in microglia. [ABSTRACT FROM AUTHOR]

Although avoidance is a prevalent feature of anxiety-related psychopathology, differences in the measurement of avoidance between humans and non-human animals hinder our progress in its theoretical understanding and treatment. To address this, we developed a novel translational measure of anxiety-related avoidance in the form of an approach-avoidance reinforcement learning task, by adapting a paradigm from the non-human animal literature to study the same cognitive processes in human participants. We used computational modelling to probe the putative cognitive mechanisms underlying approach-avoidance behaviour in this task and investigated how they relate to subjective task-induced anxiety. In a large online study (n = 372), participants who experienced greater task-induced anxiety avoided choices associated with punishment, even when this resulted in lower overall reward. Computational modelling revealed that this effect was explained by greater individual sensitivities to punishment relative to rewards. We replicated these findings in an independent sample (n = 627) and we also found fair-to-excellent reliability of measures of task performance in a sub-sample retested 1 week later (n = 57). Our findings demonstrate the potential of approach-avoidance reinforcement learning tasks as translational and computational models of anxiety-related avoidance. Future studies should assess the predictive validity of this approach in clinical samples and experimental manipulations of anxiety. [ABSTRACT FROM AUTHOR]

Background: In clinical studies, psychedelics including psilocybin and D-lysergic acid diethylamide (LSD) demonstrate rapid and persistent antidepressant effects. Since the effective treatment with psychedelics is usually provided with psychotherapy, it is debatable whether their prolonged efficacy can be observed in infrahuman species. Preclinical reports on psychedelics' effects most often address their acute actions, and different tests and models provide inconsistent results. The goal of this study was to examine whether the treatment with psilocybin and/or LSD would demonstrate immediate and/or sustained antidepressant-like effects in the differential reinforcement of low-rate responding (DRL) schedule in rats. In contrast to the antidepressant screening tools, the DRL 72s test is known to detect antidepressants with high predictive validity as it differentiates clinically effective antidepressants from other psychoactive drugs in non-stressed animals. Methods: Adult male Sprague Dawley rats were injected over three consecutive days with psilocybin (1 mg/kg), LSD (0.08 mg/kg), or saline and then tested in DRL 72s for the following 4 weeks. Results: Treatment with psilocybin but not LSD demonstrated an immediate antidepressant-like effect, manifested as an increased number of reinforced presses and response efficiency. By contrast, neither of the drugs showed a long-term (up to 4 weeks following administration) antidepressant-like effect. Conclusions: Using DRL 72s schedule of reinforcement, we demonstrated the acute antidepressant-like effect of psilocybin but not of LSD, and failed to detect their persistent antidepressant-like efficacy. The present study suggests that the detection of long-lasting antidepressant-like activity in rats could be challenging and may require entirely novel behavioral methods. [ABSTRACT FROM AUTHOR]

Implementation intentions (strategic "if-then" plans) have been shown to support behaviour change. This may be achieved by mentally forming stimulus-response associations, thereby promoting habit formation. Does this deliberate attempt to instal "strategic automaticity" only offer advantages, or does it also come at the cost of reduced flexibility that characterises learnt habits? To investigate this, we tested healthy, young participants on a computerised instrumental learning task. Critically, we introduced implementation intentions ("if I see stimulus X, then I will respond") versus goal intentions ("for outcome Z, I will respond)" during instrumental acquisition, and subsequently assessed behavioural flexibility in an outcome-revaluation test. In Experiment 1, we conducted a between-subjects manipulation of strategic planning, and in Experiment 2, a within-subject manipulation. We hypothesised that implementation intentions would lead to strong stimulus-response associations and consequently impair performance when the signalled outcome value changed and therefore required a different response, while benefitting performance when the outcome value (and required response) remained the same. We found that implementation intentions supported instrumental learning, but impaired test performance overall (most robustly in Experiment 2), irrespective of whether the signalled outcome value had changed. We argue that this general detrimental effect of implementation intentions on test performance is likely a consequence of their negative effect on stimulus-outcome learning. Our findings warrant caution when applying if-then plans to situations where the agent does not already possess perfect knowledge of behavioural contingencies.While implementation intentions may support efficient and fast behavioural execution, this may come at the expense of behavioural flexibility. [ABSTRACT FROM AUTHOR]

Introduction: Women are more vulnerable to cocaine's reinforcing effects and have a more rapid course to addiction after initial cocaine use as compared to men. Studies in rodents similarly indicate an enhanced sensitivity to the reinforcing effects of cocaine in females versus males. Levels of estradiol (E2) are correlated with vulnerability to the rewarding actions of cocaine. Here, we asked if sex chromosome complement (SCC) influences vulnerability to cocaine use. Methods: We used the four-core genotype mouse that produces gonadal males and females with either XX or XY SCC. Mice were gonadectomized and implanted with either an estradiol (E2) or cholesterol-filled pellet. This allowed us to determine the effects of SCC in the absence (cholesterol-treated) and presence of tonic high physiological hormone levels (estradiol). Acquisition of cocaine self-administration was determined over a 12-day period using an escalated dose procedure (0.3 mg/kg/infusion, sessions 1–6; 0.6 mg/kg/infusion, sessions 6–12). Results: Without estradiol treatment, a greater percentage of castrated XY mice acquired cocaine self-administration and did so at a faster rate than XX castrates and ovariectomized XY females. These same XY males acquired sooner, infused more cocaine, and directed more nose pokes to the rewarded nose-poke hole than XX castrates and XY males receiving E2. Conclusion: Our results suggest that in gonadal male mice, SCC and estradiol can modulate the reinforcing effects of cocaine which may influence the likelihood of cocaine use. [ABSTRACT FROM AUTHOR]

Mesolimbic dopamine (DA) regulates vigor in motivated behavior. While previous results have mainly been performed in male rodents, the present studies compared CD1 male and female mice in effort-based decision-making tests of motivation. These tests offered choices between several reinforcers that require different levels of effort (progressive ratio/choice task and 3-choice-T-maze task). Sweet reinforcers were used in both tasks. In the operant tasks, females worked harder as the task required more effort to access a 10% sucrose solution. Although males and females did not differ in preference for 10% vs 3% solutions under free concurrent presentation, females consumed more of the 10% solution when tested alone. The operant task requires a long period of training and changes in the DA system due to age can be mediating long-term changes in effort. Thus, age and sex factors were evaluated in the T-maze task, which requires only a short training period. Both sexes and ages were equally active when habituated to the running wheel (RW), but females consumed more sweet pellets than males, especially at an older age. Both sexes had a strong preference for the RW compared to more sedentary reinforcers in the 3-choice-T-maze test, but older animals spent less time running and ate more than the young ones. The DA-depleting agent tetrabenazine reduced time running in older mice but not in adolescents. Cerebral-dopamine-neurotrophic-factor was reduced in older mice of both sexes compared to adolescent mice. These results emphasize the importance of taking into account differences in sex and age when evaluating willingness to exert effort for specific reinforcers. [ABSTRACT FROM AUTHOR]

Reward sensitivity is an essential dimension related to mood fluctuations in bipolar disorder (BD), but there is currently a debate around hypersensitivity or hyposensitivity hypotheses to reward in BD during remission, probably related to a heterogeneous population within the BD spectrum and a lack of reward bias evaluation. Here, we examine reward maximization vs. punishment avoidance learning within the BD spectrum during remission. Patients with BD-I (n = 45), BD-II (n = 34) and matched (n = 30) healthy controls (HC) were included. They performed an instrumental learning task designed to dissociate reward-based from punishment-based reinforcement learning. Computational modeling was used to identify the mechanisms underlying reinforcement learning performances. Behavioral results showed a significant reward learning deficit across BD subtypes compared to HC, captured at the computational level by a lower sensitivity to rewards compared to punishments in both BD subtypes. Computational modeling also revealed a higher choice randomness in BD-II compared to BD-I that reflected a tendency of BD-I to perform better during punishment avoidance learning than BD-II. Our patients were not naive to antipsychotic treatment and were not euthymic (but in syndromic remission) according to the International Society for Bipolar Disorder definition. Our results are consistent with the reward hyposensitivity theory in BD. Computational modeling suggests distinct underlying mechanisms that produce similar observable behaviors, making it a useful tool for distinguishing how symptoms interact in BD versus other disorders. In the long run, a better understanding of these processes could contribute to better prevention and management of BD. • Participants with bipolar disorder showed impaired reward-based learning performance compared with control participants • Participants with bipolar disorder showed a hyposensitivity to reward compared to punishments • Patients with the BD-II subtype showed a high degree of choice variability at the computational level compared to the BD-I [ABSTRACT FROM AUTHOR]

Glyphosate, a herbicide marketed as Roundup, is widely used but there are concerns this exposure could impair cognitive function. In the CA1 region of rat hippocampal slices, we investigated whether glyphosate alters synaptic transmission and long-term potentiation (LTP), a cellular model of learning and memory. Our hypothesis is that glyphosate alters neuronal function and impairs LTP induction via activation of pro-inflammatory processes. Roundup depressed excitatory synaptic potentials(EPSPs) in a dose-dependent manner with complete suppression at 2000 mg/L. At concentrations ≤ 20 mg/L Roundup did not affect basal transmission, but 4 mg/L Roundup administered for 30 min inhibited LTP induction. Acute administration of 10–100 μM glyphosate also inhibited LTP induction. Minocycline, an inhibitor of microglial activation, and TAK-242, an inhibitor of toll-like receptor 4 (TLR4), both overcame the inhibitory effects of 100 µM glyphosate. Similarly, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), a different TLR4 antagonist, overcame the inhibitory effects. In addition, ISRIB (integrated stress response inhibitor) and quercetin, an inhibitor of endoplasmic reticulum stress, overcame the inhibitory effects. We also observed that in vivo glyphosate injection (16.9 mg/kg i.p.) impaired one-trial inhibitory avoidance learning. This learning deficit was overcome by TAK-242. These observations indicate that glyphosate can impair cognitive function through pro-inflammatory signaling in microglia. [ABSTRACT FROM AUTHOR]

Major depressive disorder often originates in adolescence and is associated with long-term functional impairment. Mechanistically characterizing this heterogeneous illness could provide important leads for optimizing treatment. Importantly, reward learning is known to be disrupted in depression. In this pilot fMRI study of 21 adolescents (16–20 years), we assessed how reward network disruption impacts specifically on Bayesian belief representations of self-efficacy (SE-B) and their associated uncertainty (SE-U), using a modified instrumental learning task probing activation induced by the opportunity to choose, and an optimal Hierarchical Gaussian Filter computational model. SE-U engaged caudate, nucleus accumbens (NAcc), precuneus, posterior parietal and dorsolateral prefrontal cortex (PFWE < 0.005). Sparse partial least squares analysis identified SE-U striatal activation as associating with one's sense of perceived choice and depressive symptoms, particularly anhedonia and negative feelings about oneself. As Bayesian uncertainty modulates belief flexibility and their capacity to steer future actions, this suggests that these striatal signals may be informative developmentally, longitudinally and in assessing response to treatment. [ABSTRACT FROM AUTHOR]

To reduce bird collisions on wind turbines, Automatic Detection Systems have been developed to locate approaching birds and trigger turbines to slowdown to 2–3 rotations per minute (rpm). However, it is unknown whether birds can detect this reduced speed and avoid the turbine. We conducted an operant conditioning experiment on domestic doves (Streptopelia roseogrisea) and Harris's hawks (Parabuteo unicinctus) to assess their ability to discriminate between stationary and rotating miniature wind turbines, depending on the rotation speed and the contrast between the white blades and the background (only for doves for the latter). At high contrast, regardless of the speed tested, hawks were able to differentiate between the rotating and stationary turbines, while doves were not able to discriminate the slow‐rotating turbine (3 rpm) from the stationary one. The discrimination threshold increased to 8 rpm for the doves when the contrast was reduced. Our results suggest that the residual wind turbine speed of 2–3 rpm may not be detected by all bird species under all environmental conditions. Increasing the contrast between wind turbines and their environment may improve the detection of low‐speed rotation by some birds, otherwise, complete turbine shutdown should be recommended. [ABSTRACT FROM AUTHOR]

Praise is stated as a good performance resource that can increase the individual's sense of competence and motivate their new learning. When the literature is examined, the importance of communication with the child in parenting is emphasized, especially the power of the words used by the parents. Parental praise is expressed as parents' repetition of the desired behaviors in children and giving feedback that will make them feel warm and sensitive with their words and behaviors in order to indicate the satisfaction felt towards them. Studies emphasize that parental praise is an important method in child development and a method that parents use very often. It is reported that many parents prefer to use praise as a tool to build self-confidence in their child. In terms of positive discipline, it is assumed that praise creates a reward value as a result of operant conditioning and can affect behavioral acquisition in the child's development. The type of parental praise plays an important role in how children form their self-image. It is in these early relationships that children first begin to feel capable, competent, and loved. Although praise is expressed as a source of motivation when it cannot be used beneficially, it can become harmful to the child when used incorrectly or excessively. At this point, the content of the praise is important. In this study, the concept of parental praise is discussed, the content of praise, which is seen as a reference to motivation, is examined and its benefits for child development are tried to be explained. [ABSTRACT FROM AUTHOR]