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Journal of Visualized Experiments : JoVE Oct 2021This protocol describes a new paradigm for analyzing aversive associative learning in adult flies (Drosophila melanogaster). The paradigm is analogous to passive...
This protocol describes a new paradigm for analyzing aversive associative learning in adult flies (Drosophila melanogaster). The paradigm is analogous to passive avoidance behavior in laboratory rodents in which animals learn to avoid a compartment where they have previously received an electric shock. The assay takes advantage of negative geotaxis in flies, which manifests as an urge to climb up when they are placed on a vertical surface. The setup consists of vertically oriented upper and lower compartments. On the first trial, a fly is placed into a lower compartment from where it usually exits within 3-15 s, and steps into the upper compartment where it receives an electric shock. During the second trial, 24 h later, the latency is significantly increased. At the same time, the number of shocks is decreased compared to the first trial, indicating that flies formed long-term memory about the upper compartment. The recordings of latencies and number of shocks could be performed with a tally counter and a stopwatch or with an Arduino-based simple device. To illustrate how the assay can be used, the passive avoidance behavior of D. melanogaster and D. simulans male and female were characterized here. Comparison of latencies and number of shocks revealed that both D. melanogaster and D. simulans flies efficiently learned the passive avoidance behavior. No statistical differences were observed between male and female flies. However, males were a little faster while entering the upper compartment on the first trial, while females received a slightly higher number of shocks in every retention trial. The Western diet (WD) significantly impaired learning and memory in male flies while flight exercise counterbalanced this effect. Taken together, the passive avoidance behavior in flies offers a simple and reproducible assay that could be used for studying basic mechanisms of learning and memory.
Topics: Animals; Avoidance Learning; Conditioning, Classical; Drosophila; Drosophila melanogaster; Female; Male
PubMed: 34723949
DOI: 10.3791/63163 -
Behaviour Research and Therapy Jan 2024Most experimental avoidance paradigms lack either control over the experimental situation or simplify real-life avoidance behavior to a great extent, making it difficult...
Most experimental avoidance paradigms lack either control over the experimental situation or simplify real-life avoidance behavior to a great extent, making it difficult to generalize the results to the complex approach-avoidance situations that anxious individuals face in daily life. The current study aimed to examine the usability of our recently developed free-exploratory avoidance paradigm in Virtual Reality (VR) that allows for the assessment of subjective as well as behavioral avoidance in participants with varying levels of spider fear. In a VR escape room, participants searched for cues to decipher a code-locked door. Opening a wooden box marked with a post-it note (conditioned stimulus, CS) resulted in exposure to a virtual crawling spider (unconditioned stimulus, US). Avoidance of the original CS and other objects marked with the CS (generalization stimuli, GSs; EXPgen condition) or non-marked (CONT condition) objects was measured via questionnaires and relative manipulation times in a novel room. We expected a positive linear relationship between US aversiveness (levels of spider fear) and (generalization of) fear and avoidance behaviors. Avoidance learning and generalization was demonstrated on both a subjective and behavioral level. Higher levels of spider fear were, overall, related to more negative emotions in response to the encounter with the spider, higher US expectancies for the GSs, and more self-reported and behavioral avoidance of the original CS and the GSs. Finally, we explored relationships between trait anxiety and intolerance of uncertainty and fear and avoidance (generalization), but no robust associations were observed. In conclusion, we confirmed the expected positive linear relationship between spider fear and (generalization of) fear and avoidance behaviors. Our results suggest that our free-exploratory VR avoidance paradigm is well-suited to investigate avoidance behaviors and the generalization of avoidance.
Topics: Animals; Humans; Spiders; Fear; Phobic Disorders; Anxiety; Avoidance Learning
PubMed: 38086158
DOI: 10.1016/j.brat.2023.104442 -
The Journal of Neuroscience : the... Aug 2020Decisions under threat are crucial to survival and require integration of distinct situational features, such as threat probability and magnitude. Recent evidence from...
Decisions under threat are crucial to survival and require integration of distinct situational features, such as threat probability and magnitude. Recent evidence from human lesion and neuroimaging studies implicated anterior hippocampus (aHC) and amygdala in approach-avoidance decisions under threat, and linked their integrity to cautious behavior. Here we sought to elucidate how threat dimensions and behavior are represented in these structures. Twenty human participants (11 female) completed an approach-avoidance conflict task during high-resolution fMRI. Participants could gather tokens under threat of capture by a virtual predator, which would lead to token loss. Threat probability (predator wake-up rate) and magnitude (amount of token loss) varied on each trial. To disentangle effects of threat features, and ensuing behavior, we performed a multifold parametric analysis. We found that high threat probability and magnitude related to BOLD signal in left aHC/entorhinal cortex. However, BOLD signal in this region was better explained by avoidance behavior than by these threat features. ROI analysis confirmed the relation of aHC BOLD response with avoidance. Exploratory subfield analysis revealed that this relation was specific to anterior CA2/3 but not CA1. Left lateral amygdala responded to low and high, but not intermediate, threat probability. Our results suggest that aHC BOLD signal is better explained by avoidance behavior than by threat features in approach-avoidance conflict. Rather than representing threat features in a monotonic manner, it appears that aHC may compute approach-avoidance decisions based on integration of situational threat features represented in other neural structures. An effective threat anticipation system is crucial to survival across species. Natural threats, however, are diverse and have distinct features. To be able to adapt to different modes of danger, the brain needs to recognize these features, integrate them, and use them to modify behavior. Our results disclose the human anterior hippocampus as a likely arbiter of approach-avoidance decisions harnessing compound environmental information while partially replicating previous findings and blending into recent efforts to illuminate the neural basis of approach-avoidance conflict in humans.
Topics: Adult; Amygdala; Anxiety; Avoidance Learning; Choice Behavior; Conflict, Psychological; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male
PubMed: 32719163
DOI: 10.1523/JNEUROSCI.2732-19.2020 -
Behaviour Research and Therapy Dec 2020Maladaptive avoidance behaviour, a key symptom of anxiety-related disorders, prevents extinction learning and maintains anxiety. Individual personality traits likely...
Maladaptive avoidance behaviour, a key symptom of anxiety-related disorders, prevents extinction learning and maintains anxiety. Individual personality traits likely influence avoidance propensity: high sensation-seeking may decrease avoidance, thereby increasing extinction, and neuroticism may have the reverse effect. However, research on this is scarce. Using a naturalistic conditioned avoidance paradigm, 163 women underwent differential fear acquisition to a conditioned stimulus (CSplus). Next, during extinction, participants could either choose a risky shortcut, anticipating shock signalled by CSplus, or a time-consuming avoidance option (lengthy detour). Across participants, increased skin conductance (SCR) acquisition learning predicted subsequent instrumental avoidance. Avoidance, in turn, predicted elevated post-extinction SCR and shock-expectancy, i.e., 'protection-from-extinction'. Mediation analyses revealed that sensation seeking decreased protection-from-extinction-both for shock-expectancy and SCR-via attenuating avoidance. Neither sensation seeking nor neuroticism were related to acquisition learning and neuroticism was neither related to avoidance nor extinction. Transcranial direct currentstimulation administered before extinction did not influence present results. Results highlight the important role of elevated avoidance propensity in fear maintenance. Results moreover provide evidence for reduced sensation-seeking and increased acquisition learning to be avoidance-driving mechanisms. Since approach-avoidance conflicts are faced by anxiety patients on a daily basis, strengthening sensation-seeking-congruent attitudes and approach behaviours may optimize individualized treatment.
Topics: Avoidance Learning; Conditioning, Classical; Extinction, Psychological; Fear; Female; Galvanic Skin Response; Humans; Neuroticism; Young Adult
PubMed: 33186828
DOI: 10.1016/j.brat.2020.103761 -
Behaviour Research and Therapy Jun 2022Positive affect is hypothesized to improve safety learning taking place during extinction (i.e., the core mechanism of exposure treatment), therefore improving the...
Positive affect is hypothesized to improve safety learning taking place during extinction (i.e., the core mechanism of exposure treatment), therefore improving the maintenance of treatment outcomes. We investigated whether positive affect during extinction attenuates the subsequent return of pain-related avoidance and fear. In an operant pain-related avoidance conditioning paradigm, sixty healthy volunteers performed arm-reaching movements using a robotic arm. During acquisition, they learned to avoid an easy but painful movement (T1) by choosing more effortful movements that were sometimes (T2) or never (T3) painful. Then, the Positive affect group wrote about and imagined their best possible self, which is known to induce positive affect, whereas the Control group wrote about and imagined a typical day. During extinction with response prevention (RPE), participants were only allowed to perform T1, which was no longer paired with pain. Next, two painful stimuli were presented when participants were not moving (i.e., reinstatement manipulation). During test, all movements were available, and we examined whether fear and avoidance of the previously painful movements would re-emerge. Pain-related avoidance returned in both groups, but the two groups did not differ herein. The Positive affect group reported increased positive affect, though not more than the Control group. Nevertheless, they generalized the learned safety of T1 to the other movements during RPE, whereas they also retrospectively rated the pain as less intense and less unpleasant. These results add to the literature of positive affect as a resilience factor.
Topics: Avoidance Learning; Conditioning, Operant; Extinction, Psychological; Fear; Humans; Pain; Retrospective Studies
PubMed: 35468524
DOI: 10.1016/j.brat.2022.104080 -
Nature Communications Dec 2022Early-life adversity (ELA) increases the likelihood of neuropsychiatric diagnoses, which are more prevalent in women than men. Since changes in reproductive hormone...
Early-life adversity (ELA) increases the likelihood of neuropsychiatric diagnoses, which are more prevalent in women than men. Since changes in reproductive hormone levels can also increase the probability of anxiety disorders in women, we examined the effects of ELA on adult female mice across the estrous cycle. We found that during diestrus, when progesterone levels are relatively high, ELA mice exhibit increased avoidance behavior and increased theta oscillation power in the ventral hippocampus (vHIP). We also found that diestrus ELA mice had higher levels of progesterone and lower levels of allopregnanolone, a neurosteroid metabolite of progesterone, in the vHIP compared with control-reared mice. Progesterone receptor antagonism normalized avoidance behavior in ELA mice, while treatment with a negative allosteric modulator of allopregnanolone promoted avoidance behavior in control mice. These results suggest that altered vHIP progesterone and allopregnanolone signaling during diestrus increases avoidance behavior in ELA mice.
Topics: Animals; Female; Mice; Avoidance Learning; Estrous Cycle; Progesterone; Pregnanolone
PubMed: 36476469
DOI: 10.1038/s41467-022-35068-w -
Neuropsychopharmacology : Official... Jul 2023The bed nucleus of the stria terminalis (BNST) is a forebrain region implicated in aversive responses to uncertain threat. Much of the work on the role of BNST in...
The bed nucleus of the stria terminalis (BNST) is a forebrain region implicated in aversive responses to uncertain threat. Much of the work on the role of BNST in defensive behavior has used Pavlovian paradigms in which the subject reacts to aversive stimuli delivered in a pattern determined entirely by the experimenter. Here, we explore the contribution of BNST to a task in which subjects learn a proactive response that prevents the delivery of an aversive outcome. To this end, male and female rats were trained to shuttle during a tone to avoid shock in a standard two-way signaled active avoidance paradigm. Chemogenetic inhibition (hM4Di) of BNST attenuated the expression of the avoidance response in male but not female rats. Inactivation of the neighboring medial septum in males produced no effect on avoidance, demonstrating that our effect was specific to BNST. A follow up study comparing hM4Di inhibition to hM3Dq activation of BNST in males replicated the effect of inhibition and demonstrated that activation of BNST extended the period of tone-evoked shuttling. These data support the novel conclusion that BNST mediates two-way avoidance behavior in male rats and suggest the intriguing possibility that the systems underlying proactive defensive behavior are sex-specific.
Topics: Female; Rats; Male; Animals; Septal Nuclei; Follow-Up Studies; Avoidance Learning
PubMed: 37142666
DOI: 10.1038/s41386-023-01581-9 -
Behavioural Brain Research Sep 2020Avoidance behavior is a typically adaptive response performed by an organism to avert harmful situations. Individuals differ remarkably in their tendency to acquire and...
Avoidance behavior is a typically adaptive response performed by an organism to avert harmful situations. Individuals differ remarkably in their tendency to acquire and perform new avoidance behaviors, as seen in anxiety disorders where avoidance becomes pervasive and inappropriate. In rodent models of avoidance, the inbred Wistar-Kyoto (WKY) rat demonstrates increased learning and expression of avoidance compared to the outbred Sprague Dawley (SD) rat. However, underlying mechanisms that contribute to these differences are unclear. Computational modeling techniques can help identify factors that may not be easily decipherable from behavioral data alone. Here, we utilize a reinforcement learning (RL) model approach to better understand strain differences in avoidance behavior. An actor-critic model, with separate learning rates for action selection (in the actor) and state evaluation (in the critic), was applied to individual data of avoidance acquisition from a large cohort of WKY and SD rats. Latent parameters were extracted, such as learning rate and subjective reinforcement value of foot shock, that were then compared across groups. The RL model was able to accurately represent WKY and SD avoidance behavior, demonstrating that the model could simulate individual performance. The model determined that the perceived negative value of foot shock was significantly higher in WKY than SD rats, whereas learning rate in the actor was lower in WKY than SD rats. These findings demonstrate the utility of computational modeling in identifying underlying processes that could promote strain differences in behavioral performance.
Topics: Animals; Avoidance Learning; Models, Psychological; Rats, Inbred WKY; Rats, Sprague-Dawley; Reinforcement, Psychology; Species Specificity
PubMed: 32585299
DOI: 10.1016/j.bbr.2020.112784 -
Psychiatry and Clinical Neurosciences Sep 2021Psychiatric symptoms are often accompanied by impairments in decision-making to attain rewards and avoid losses. However, due to the complex nature of mental disorders...
AIM
Psychiatric symptoms are often accompanied by impairments in decision-making to attain rewards and avoid losses. However, due to the complex nature of mental disorders (e.g., high comorbidity), symptoms that are specifically associated with deficits in decision-making remain unidentified. Furthermore, the influence of psychiatric symptoms on computations underpinning reward-seeking and loss-avoidance decision-making remains elusive. Here, we aim to address these issues by leveraging a large-scale online experiment and computational modeling.
METHODS
In the online experiment, we recruited 1900 non-diagnostic participants from the general population. They performed either a reward-seeking or loss-avoidance decision-making task, and subsequently completed questionnaires about psychiatric symptoms.
RESULTS
We found that one trans-diagnostic dimension of psychiatric symptoms related to compulsive behavior and intrusive thought (CIT) was negatively correlated with overall decision-making performance in both the reward-seeking and loss-avoidance tasks. A deeper analysis further revealed that, in both tasks, the CIT psychiatric dimension was associated with lower preference for the options that recently led to better outcomes (i.e. reward or no-loss). On the other hand, in the reward-seeking task only, the CIT dimension was associated with lower preference for recently unchosen options.
CONCLUSION
These findings suggest that psychiatric symptoms influence the two types of decision-making, reward-seeking and loss-avoidance, through both common and distinct computational processes.
Topics: Adult; Aged; Avoidance Learning; Computer Simulation; Decision Making; Female; Humans; Male; Mental Disorders; Middle Aged; Models, Psychological; Reward; Young Adult
PubMed: 34151477
DOI: 10.1111/pcn.13279 -
Psychopharmacology Aug 2019Aversive stimuli in the environment influence human actions. This includes valence-dependent influences on action selection, e.g., increased avoidance but decreased... (Clinical Trial)
Clinical Trial
BACKGROUND
Aversive stimuli in the environment influence human actions. This includes valence-dependent influences on action selection, e.g., increased avoidance but decreased approach behavior. However, it is yet unclear how aversive stimuli interact with complex learning and decision-making in the reward and avoidance domain. Moreover, the underlying computational mechanisms of these decision-making biases are unknown.
METHODS
To elucidate these mechanisms, 54 healthy young male subjects performed a two-step sequential decision-making task, which allows to computationally model different aspects of learning, e.g., model-free, habitual, and model-based, goal-directed learning. We used a within-subject design, crossing task valence (reward vs. punishment learning) with emotional context (aversive vs. neutral background stimuli). We analyzed choice data, applied a computational model, and performed simulations.
RESULTS
Whereas model-based learning was not affected, aversive stimuli interacted with model-free learning in a way that depended on task valence. Thus, aversive stimuli increased model-free avoidance learning but decreased model-free reward learning. The computational model confirmed this effect: the parameter lambda that indicates the influence of reward prediction errors on decision values was increased in the punishment condition but decreased in the reward condition when aversive stimuli were present. Further, by using the inferred computational parameters to simulate choice data, our effects were captured. Exploratory analyses revealed that the observed biases were associated with subclinical depressive symptoms.
CONCLUSION
Our data show that aversive environmental stimuli affect complex learning and decision-making, which depends on task valence. Further, we provide a model of the underlying computations of this affective modulation. Finally, our finding of increased decision-making biases in subjects reporting subclinical depressive symptoms matches recent reports of amplified Pavlovian influences on action selection in depression and suggests a potential vulnerability factor for mood disorders. We discuss our findings in the light of the involvement of the neuromodulators serotonin and dopamine.
Topics: Affect; Avoidance Learning; Choice Behavior; Computer Simulation; Decision Making; Depression; Humans; Male; Models, Psychological; Photic Stimulation; Punishment; Reward; Young Adult
PubMed: 31254091
DOI: 10.1007/s00213-019-05299-9