-
Journal of Biomedical Science Dec 2021Addictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted... (Review)
Review
Addictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted animals have only unlearned reflexes; they lack learned seeking and learned avoidance. Burst-firing of dopamine neurons enables learning-long-term potentiation (LTP)-of search and avoidance responses. It sets the stage for learning that occurs between glutamatergic sensory inputs and GABAergic motor-related outputs of the striatum; this learning establishes the ability to search and avoid. Independent of burst-firing, the rate of single-spiking-or "pacemaker firing"-of dopaminergic neurons mediates motivational arousal. Motivational arousal increases during need states and its level determines the responsiveness of the animal to established predictive stimuli. Addictive drugs, while usually not serving as an external stimulus, have varying abilities to activate the dopamine system; the comparative abilities of different addictive drugs to facilitate LTP is something that might be studied in the future.
Topics: Animals; Appetitive Behavior; Avoidance Learning; Behavior, Addictive; Dopamine; Dopaminergic Neurons; Learning; Long-Term Potentiation; Mice; Rats; Reflex
PubMed: 34852810
DOI: 10.1186/s12929-021-00779-7 -
Nature Neuroscience Nov 2021The basolateral amygdala (BLA) plays essential roles in behaviors motivated by stimuli with either positive or negative valence, but how it processes motivationally...
The basolateral amygdala (BLA) plays essential roles in behaviors motivated by stimuli with either positive or negative valence, but how it processes motivationally opposing information and participates in establishing valence-specific behaviors remains unclear. Here, by targeting Fezf2-expressing neurons in the BLA, we identify and characterize two functionally distinct classes in behaving mice, the negative-valence neurons and positive-valence neurons, which innately represent aversive and rewarding stimuli, respectively, and through learning acquire predictive responses that are essential for punishment avoidance or reward seeking. Notably, these two classes of neurons receive inputs from separate sets of sensory and limbic areas, and convey punishment and reward information through projections to the nucleus accumbens and olfactory tubercle, respectively, to drive negative and positive reinforcement. Thus, valence-specific BLA neurons are wired with distinctive input-output structures, forming a circuit framework that supports the roles of the BLA in encoding, learning and executing valence-specific motivated behaviors.
Topics: Amygdala; Animals; Attention; Avoidance Learning; Corpus Striatum; DNA-Binding Proteins; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motivation; Nerve Net; Nerve Tissue Proteins
PubMed: 34663958
DOI: 10.1038/s41593-021-00927-0 -
Nature Apr 2023The central amygdala (CeA) is implicated in a range of mental processes including attention, motivation, memory formation and extinction and in behaviours driven by...
The central amygdala (CeA) is implicated in a range of mental processes including attention, motivation, memory formation and extinction and in behaviours driven by either aversive or appetitive stimuli. How it participates in these divergent functions remains elusive. Here we show that somatostatin-expressing (Sst) CeA neurons, which mediate much of CeA functions, generate experience-dependent and stimulus-specific evaluative signals essential for learning. The population responses of these neurons in mice encode the identities of a wide range of salient stimuli, with the responses of separate subpopulations selectively representing the stimuli that have contrasting valences, sensory modalities or physical properties (for example, shock and water reward). These signals scale with stimulus intensity, undergo pronounced amplification and transformation during learning, and are required for both reward and aversive learning. Notably, these signals contribute to the responses of dopamine neurons to reward and reward prediction error, but not to their responses to aversive stimuli. In line with this, Sst CeA neuron outputs to dopamine areas are required for reward learning, but are dispensable for aversive learning. Our results suggest that Sst CeA neurons selectively process information about differing salient events for evaluation during learning, supporting the diverse roles of the CeA. In particular, the information for dopamine neurons facilitates reward evaluation.
Topics: Animals; Mice; Avoidance Learning; Central Amygdaloid Nucleus; Dopaminergic Neurons; Motivation; Reward; Neuronal Plasticity; Somatostatin; Electroshock
PubMed: 37020025
DOI: 10.1038/s41586-023-05910-2 -
Medicine and Science in Sports and... Jul 2020This study aimed to examine the effects of treadmill training on anxious-depressive-like behaviors of transgenic Alzheimer rats in the early stage of Alzheimer's disease...
PURPOSE
This study aimed to examine the effects of treadmill training on anxious-depressive-like behaviors of transgenic Alzheimer rats in the early stage of Alzheimer's disease (AD) and provided evidence of exercise in alleviating fear-avoidance behavior deficits.
METHODS
Male 2-month-old TgF344-AD and wild-type rats were divided into wild-type (n = 9), AD (n = 8), and AD + treadmill exercise (Exe) groups (n = 12). After 8 months of exercise, the passive avoidance test, Barnes maze task, novel object recognition test, and object location test were used to measure learning and memory function. The open-field test, elevated plus maze, sucrose preference test, and forced swim test were conducted to determine the anxious-depressive-like behavior of AD rats. Immunofluorescence staining, Western blot analysis, enzyme-linked immunosorbent assay analysis, and related assay kits were used to measure inflammatory cytokines, oxidative stress, amyloid-β production, and tau hyperphosphorylation.
RESULTS
Behavioral tests revealed that 12-month-old animals did not show any spatial learning and memory deficits but did display anxious-depressive-like behavior (open field, center time: P = 0.008; center entries: P = 0.009; line crossings: P = 0.001). However, long-term exercise significantly inhibited anxious-depressive-like behavior in AD rats (center time: P = 0.016; center entries: P = 0.004; line crossings: P = 0.033). In addition, these animals displayed increased amyloid-β deposition, tau hyperphosphorylation, microgliosis, inflammatory cytokines release, and oxidative damage, which were attenuated significantly by long-term exercise training.
CONCLUSION
Long-term exercise training alleviated anxious-depressive-like behavior and improved fear-avoidance behavior in transgenic AD rats, supporting exercise training as an effective approach to prevent anxiety, depression, and fear-avoidance behavior deficits in the early stages of AD pathogenesis.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Anxiety; Avoidance Learning; Cerebral Cortex; Cytokines; Depression; Disease Models, Animal; Fear; Hippocampus; Male; Microglia; Oxidative Stress; Phosphorylation; Physical Conditioning, Animal; Rats, Inbred F344; Receptors, Serotonin; Serotonin; tau Proteins
PubMed: 32028456
DOI: 10.1249/MSS.0000000000002294 -
Neuroscience and Biobehavioral Reviews Jan 2020Every day we are bombarded by stimuli that must be assessed for their potential for harm or benefit. Once a stimulus is learned to predict harm, it can elicit fear... (Review)
Review
Every day we are bombarded by stimuli that must be assessed for their potential for harm or benefit. Once a stimulus is learned to predict harm, it can elicit fear responses. Such learning can last a lifetime but is not always beneficial for an organism. For an organism to thrive in its environment, it must know when to engage in defensive, avoidance behaviors and when to engage in non-defensive, approach behaviors. Fear should be suppressed in situations that are not dangerous: when a novel, innocuous stimulus resembles a feared stimulus, when a feared stimulus no longer predicts harm, or when there is an option to avoid harm. A cardinal feature of anxiety disorders is the inability to suppress fear adaptively. In PTSD, for instance, learned fear is expressed inappropriately in safe situations and is resistant to extinction. In this review, we discuss mechanisms of suppressing fear responses during stimulus discrimination, fear extinction, and active avoidance, focusing on the well-studied tripartite circuit consisting of the amygdala, medial prefrontal cortex and hippocampus.
Topics: Amygdala; Animals; Avoidance Learning; Discrimination Learning; Extinction, Psychological; Fear; Generalization, Psychological; Hippocampus; Humans; Prefrontal Cortex; Safety
PubMed: 31738952
DOI: 10.1016/j.neubiorev.2019.11.006 -
Nature Neuroscience Oct 2021The appropriate selection of passive and active defensive behaviors in threatening situations is essential for survival. Previous studies have shown that passive...
The appropriate selection of passive and active defensive behaviors in threatening situations is essential for survival. Previous studies have shown that passive defensive responses depend on activity of the central nucleus of the amygdala (CeA), whereas active ones primarily rely on the nucleus accumbens (NAc). However, the mechanisms underlying flexible switching between these two types of responses remain unknown. Here we show in mice that the paraventricular thalamus (PVT) mediates the selection of defensive behaviors through its interaction with the CeA and the NAc. We show that the PVT-CeA pathway drives conditioned freezing responses, whereas the PVT-NAc pathway is inhibited during freezing and, instead, signals active avoidance events. Optogenetic manipulations revealed that activity in the PVT-CeA or PVT-NAc pathway biases behavior toward the selection of passive or active defensive responses, respectively. These findings provide evidence that the PVT mediates flexible switching between opposing defensive behaviors.
Topics: Animals; Avoidance Learning; Behavior, Animal; Mice; Mice, Inbred C57BL; Neural Pathways; Optogenetics; Paraventricular Hypothalamic Nucleus
PubMed: 34413514
DOI: 10.1038/s41593-021-00912-7 -
Physical Therapy Dec 2020Physical activity and exercise are central components in rehabilitation after a myocardial infarction. Kinesiophobia (fear of movement) is a well-known barrier for a...
OBJECTIVE
Physical activity and exercise are central components in rehabilitation after a myocardial infarction. Kinesiophobia (fear of movement) is a well-known barrier for a good rehabilitation outcome in these patients; however, there is a lack of studies focusing on the patient perspective. The aim of this study was to explore patients' perceptions of kinesiophobia in relation to physical activity and exercise 2 to 3 months after an acute myocardial infarction.
METHODS
This qualitative study design used individual semi-structured interviews. Face-to-face interviews were conducted with 21 patients post-myocardial infarction who were screened for kinesiophobia (≥32 on the Tampa Scale for Kinesiophobia Heart). The interviews were transcribed and analyzed according to an inductive content analysis.
RESULTS
An overarching theme was defined as "coping with fear of movement after a myocardial infarction-a dynamic process over time" comprising 2 subthemes and explaining how coping with kinesiophobia runs in parallel processes integrating the patient's internal process and a contextual external process. The 2 processes are described in a total of 8 categories. The internal process was an iterative process governed by a combination of factors: ambivalence, hypervigilance, insecurity about progression, and avoidance behavior. The external process contains the categories of relatives' anxiety, prerequisites for feeling safe, information, and the exercise-based cardiac rehabilitation program.
CONCLUSION
Coping with fear of movement after a myocardial infarction is a dynamic process that requires internal and external support. To further improve cardiac rehabilitation programs, person-centered strategies that support the process of each person-as well as new treatment strategies to reduce kinesiophobia-need to be elaborated.
IMPACT
Patients with a myocardial infarction were found to be ambivalent about how they expressed their fear of movement; therefore, it is crucial for physical therapists to acknowledge signs of fear by listening carefully to the patient's full story in addition to using adequate self-reports and tests of physical fitness. These results will inform the design, development, and evaluation of new treatment strategies, with the overall aim of reducing kinesiophobia and increasing physical activity and participation in exercise-based cardiac rehabilitation.
Topics: Adaptation, Psychological; Adult; Aged; Aged, 80 and over; Anxiety; Avoidance Learning; Cardiac Rehabilitation; Exercise; Family; Female; Humans; Male; Middle Aged; Movement; Myocardial Infarction; Patient Education as Topic; Phobic Disorders; Qualitative Research; Sweden; Symptom Assessment
PubMed: 32886775
DOI: 10.1093/ptj/pzaa159 -
Neuroscience and Biobehavioral Reviews Dec 2020All animals are under the constant threat of attack by parasites. The mere presence of parasite threat can alter behavior before infection takes place. These effects... (Review)
Review
All animals are under the constant threat of attack by parasites. The mere presence of parasite threat can alter behavior before infection takes place. These effects involve pathogen disgust, an evolutionarily conserved affective/emotional system that functions to detect cues associated with parasites and infection and facilitate avoidance behaviors. Animals gauge the infection status of conspecific and the salience of the threat they represent on the basis of various sensory cues. Odors in particular are a major source of social information about conspecifics and the infection threat they present. Here we briefly consider the origins, expression, and regulation of the fundamental features of odor mediated pathogen disgust in rodents. We briefly review aspects of: (1) the expression of affective states and emotions and in particular, disgust, in rodents; (2) olfactory mediated recognition and avoidance of potentially infected conspecifics and the impact of pathogen disgust and its' fundamental features on behavior; (3) pathogen disgust associated trade-offs; (4) the neurobiological mechanisms, and in particular the roles of the nonapeptide, oxytocin, and steroidal hormones, in the expression of pathogen disgust and the regulation of avoidance behaviors and concomitant trade-offs. Understanding the roles of pathogen disgust in rodents can provide insights into the regulation and expression of responses to pathogens and infection in humans.
Topics: Animals; Avoidance Learning; Disgust; Emotions; Odorants; Oxytocin; Rodentia
PubMed: 33031813
DOI: 10.1016/j.neubiorev.2020.09.037 -
Cell Sep 2021Animals face both external and internal dangers: pathogens threaten from the environment, and unstable genomic elements threaten from within. C. elegans protects itself...
Animals face both external and internal dangers: pathogens threaten from the environment, and unstable genomic elements threaten from within. C. elegans protects itself from pathogens by "reading" bacterial small RNAs, using this information to both induce avoidance and transmit memories for four generations. Here, we found that memories can be transferred from either lysed animals or from conditioned media to naive animals via Cer1 retrotransposon-encoded virus-like particles. Moreover, Cer1 functions internally at the step of transmission of information from the germline to neurons and is required for learned avoidance. The presence of the Cer1 retrotransposon in wild C. elegans strains correlates with the ability to learn and inherit small-RNA-induced pathogen avoidance. Together, these results suggest that C. elegans has co-opted a potentially dangerous retrotransposon to instead protect itself and its progeny from a common pathogen through its inter-tissue signaling ability, hijacking this genomic element for its own adaptive immunity benefit.
Topics: Animals; Avoidance Learning; Behavior, Animal; Caenorhabditis elegans; DNA Transposable Elements; Extracellular Vesicles; Gene Expression Regulation; Gene Transfer, Horizontal; Genome; Germ Cells; Inheritance Patterns; Memory; RNA; RNA Interference; Virion
PubMed: 34363756
DOI: 10.1016/j.cell.2021.07.022 -
Current Psychiatry Reports Jan 2021In current review, we evaluate the current literature examining the role of disgust in eating disorders (EDs), and provide a theoretical model designed to inform the... (Review)
Review
PURPOSE OF REVIEW
In current review, we evaluate the current literature examining the role of disgust in eating disorders (EDs), and provide a theoretical model designed to inform the study and treatment of disgust-based symptoms in EDs.
RECENT FINDINGS
Findings from this review suggest that aberrant disgust-conditioning processes represent promising but understudied mechanisms that may contribute to the risk and maintenance of core eating disorder (ED) psychopathology. In addition, preliminary evidence supports the use of interventions designed to target aversive disgust cues and disrupt maladaptive disgust-based conditioning that may maintain eating pathology. However, experimental studies designed to elucidate the role of disgust and aversive learning processes remain limited. Disgust is a promising risk and maintenance factor in EDs. Future systematic investigation is needed to examine disgust-based processes at a mechanistic level in order to better understand the links between disgust, avoidance behaviors, and EDs. Further investigation of the mechanistic role of disgust in EDs is warranted.
Topics: Affect; Avoidance Learning; Disgust; Feeding and Eating Disorders; Humans; Psychopathology
PubMed: 33404776
DOI: 10.1007/s11920-020-01217-5