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Cell Reports Nov 2023The subthalamic nucleus (STN) is critical for behavioral control; its dysregulation consequently correlated with neurological and neuropsychiatric disorders, including...
The subthalamic nucleus (STN) is critical for behavioral control; its dysregulation consequently correlated with neurological and neuropsychiatric disorders, including Parkinson's disease. Deep brain stimulation (DBS) targeting the STN successfully alleviates parkinsonian motor symptoms. However, low mood and depression are affective side effects. STN is adjoined with para-STN, associated with appetitive and aversive behavior. DBS aimed at STN might unintentionally modulate para-STN, causing aversion. Alternatively, the STN mediates aversion. To investigate causality between STN and aversion, affective behavior is addressed using optogenetics in mice. Selective promoters allow dissociation of STN (e.g., Pitx2) vs. para-STN (Tac1). Acute photostimulation results in aversion via both STN and para-STN. However, only STN stimulation-paired cues cause conditioned avoidance and only STN stimulation interrupts on-going sugar self-administration. Electrophysiological recordings identify post-synaptic responses in pallidal neurons, and selective photostimulation of STN terminals in the ventral pallidum replicates STN-induced aversion. Identifying STN as a source of aversive learning contributes neurobiological underpinnings to emotional affect.
Topics: Animals; Mice; Subthalamic Nucleus; Avoidance Learning; Deep Brain Stimulation; Parkinson Disease; Parkinsonian Disorders
PubMed: 37925641
DOI: 10.1016/j.celrep.2023.113328 -
Animals : An Open Access Journal From... Jan 2024The emotion of disgust in humans is widely considered to represent a continuation of the disease-avoidance behavior ubiquitous in animals. The extent to which analogs of... (Review)
Review
The emotion of disgust in humans is widely considered to represent a continuation of the disease-avoidance behavior ubiquitous in animals. The extent to which analogs of human disgust are evident in nonhuman animals, however, remains unclear. The scant research explicitly investigating disgust in animals has predominantly focused on great apes and suggests that disgust might be present in a highly muted form. In this review, we outline the main approaches to disgust. We then briefly discuss disease-avoidance behavior in nonhuman animals, proposing a set of criteria against which evidence for the presence or absence of disgust in animals can be evaluated. The resultant decision tree takes into account other plausible causes of avoidance and aversion when evaluating whether it is likely that the behavior represents disgust. We apply this decision tree to evaluate evidence of disgust-like behavior (e.g., avoidance of carrion and avoidance of feces-contaminated food) in several examples, including nonhuman great apes. Finally, we consider the large disparity between disgust in humans compared to muted disgust in other great apes, examining the possibility that heightened disgust in humans is a relatively recent cultural acquisition.
PubMed: 38254434
DOI: 10.3390/ani14020264 -
Frontiers in Neuroscience 2023Post-traumatic stress disorder (PTSD) is a stress-associated complex and debilitating psychiatric disorder due to an imbalance of neurotransmitters in response to... (Review)
Review
Post-traumatic stress disorder (PTSD) is a stress-associated complex and debilitating psychiatric disorder due to an imbalance of neurotransmitters in response to traumatic events or fear. PTSD is characterized by re-experiencing, avoidance behavior, hyperarousal, negative emotions, insomnia, personality changes, and memory problems following exposure to severe trauma. However, the biological mechanisms and symptomatology underlying this disorder are still largely unknown or poorly understood. Considerable evidence shows that PTSD results from a dysfunction in highly conserved brain systems involved in regulating stress, anxiety, fear, and reward circuitry. This review provides a contemporary update about PTSD, including new data from the clinical and preclinical literature on stress, PTSD, and fear memory consolidation and extinction processes. First, we present an overview of well-established laboratory models of PTSD and discuss their clinical translational value for finding various treatments for PTSD. We then highlight the research progress on the neural circuits of fear and extinction-related behavior, including the prefrontal cortex, hippocampus, and amygdala. We further describe different molecular mechanisms, including GABAergic, glutamatergic, cholinergic, and neurotropic signaling, responsible for the structural and functional changes during fear acquisition and fear extinction processes in PTSD.
PubMed: 38116070
DOI: 10.3389/fnins.2023.1281401 -
PeerJ 2023The purpose of this study is to present the development and analysis of the factorial structure and psychometric properties of a new self-administered questionnaire... (Observational Study)
Observational Study
The purpose of this study is to present the development and analysis of the factorial structure and psychometric properties of a new self-administered questionnaire (Dizziness Fear-Avoidance Behaviours and Beliefs Inventory (D-FABBI)) designed to measure fear-avoidance behaviors and cognitions related to dizziness disability. A mixed-method design combining a qualitative study with an observational and cross-sectional study was employed to develop (content validity) and psychometrically validate (construct validity, reliability, and convergent/discriminant validity) a new instrument. A total of 198 patients with vestibular disorders (acute vestibular syndrome (AVS), 23.2%; chronic vestibular syndrome (CVS), 35.4%; and episodic vestibular syndrome (EVS) 41.4%) were recruited. Sociodemographic characteristics, the Dizziness Handicap Inventory (DHI) and the Hospital Anxiety and Depression Scale (HADS) and D-FABBI were evaluated. The final version of the D-FABBI consists of 17 items distributed across two subscales: activities of daily living fear-avoidance and movement fear-avoidance. The D-FABBI showed high internal consistency (Cronbach α = 0.932; 95% CI [0.91-0.94]) and so did the subscales (Cronbach α > 0.8). The exploratory structural equation model and confirmatory factor analysis provided better fit results, with a comparative fit index and root mean square error of approximation values of 0.907 to 0.081. No floor or ceiling effects were identified. There was a positive, significant, and moderate-strong magnitude correlation with the total DHI (r = 0.62) and low-moderate with respect to the HADS depression (r = 0.35) and HADS anxiety subscales (r = 0.26). The patients with CVS had a higher D-FABBI score than those with AVS or EVS. The D-FABBI appears to be a valid and reliable instrument for measuring the fear-avoidance behaviors and cognition related to dizziness disability of patients with vestibular disorders.
Topics: Humans; Activities of Daily Living; Avoidance Learning; Cross-Sectional Studies; Dizziness; Fear; Reproducibility of Results; Vertigo; Vestibular Diseases
PubMed: 37663281
DOI: 10.7717/peerj.15940 -
BMC Biology Jul 2023Rodents utilize chemical cues to recognize and avoid other conspecifics infected with pathogens. Infection with pathogens and acute inflammation alter the repertoire and...
BACKGROUND
Rodents utilize chemical cues to recognize and avoid other conspecifics infected with pathogens. Infection with pathogens and acute inflammation alter the repertoire and signature of olfactory stimuli emitted by a sick individual. These cues are recognized by healthy conspecifics via the vomeronasal or accessory olfactory system, triggering an innate form of avoidance behavior. However, the molecular identity of the sensory neurons and the higher neural circuits involved in the detection of sick conspecifics remain poorly understood.
RESULTS
We employed mice that are in an acute state of inflammation induced by systemic administration of lipopolysaccharide (LPS). Through conditional knockout of the G-protein Gαi2 and deletion of other key sensory transduction molecules (Trpc2 and a cluster of 16 vomeronasal type 1 receptors), in combination with behavioral testing, subcellular Ca imaging, and pS6 and c-Fos neuronal activity mapping in freely behaving mice, we show that the Gαi2 vomeronasal subsystem is required for the detection and avoidance of LPS-treated mice. The active components underlying this avoidance are contained in urine whereas feces extract and two selected bile acids, although detected in a Gαi2-dependent manner, failed to evoke avoidance behavior. Our analyses of dendritic Ca responses in vomeronasal sensory neurons provide insight into the discrimination capabilities of these neurons for urine fractions from LPS-treated mice, and how this discrimination depends on Gαi2. We observed Gαi2-dependent stimulation of multiple brain areas including medial amygdala, ventromedial hypothalamus, and periaqueductal grey. We also identified the lateral habenula, a brain region implicated in negative reward prediction in aversive learning, as a previously unknown target involved in these tasks.
CONCLUSIONS
Our physiological and behavioral analyses indicate that the sensing and avoidance of LPS-treated sick conspecifics depend on the Gαi2 vomeronasal subsystem. Our observations point to a central role of brain circuits downstream of the olfactory periphery and in the lateral habenula in the detection and avoidance of sick conspecifics, providing new insights into the neural substrates and circuit logic of the sensing of inflammation in mice.
Topics: Mice; Animals; Vomeronasal Organ; Lipopolysaccharides; Brain; Sensory Receptor Cells; Inflammation
PubMed: 37424020
DOI: 10.1186/s12915-023-01653-8 -
Neurobiology of Disease Jul 2023Anxiety disorders have been linked to a disbalance of excitation and inhibition in a network of brain structures comprising frontal cortical regions, the amygdala and...
Anxiety disorders have been linked to a disbalance of excitation and inhibition in a network of brain structures comprising frontal cortical regions, the amygdala and the hippocampus, among others. Recent imaging studies suggest sex differences in the activation of this anxiety network during the processing of emotional information. Rodent models with genetically altered ϒ-amino butyric acid (GABA) neurotransmission allow studying the neuronal basis of such activation shifts and their relation to anxiety endophenotypes, but to date sex effects have rarely been addressed. Using mice with a null mutation of the GABA synthetizing enzyme glutamate decarboxylase 65 (GAD65-/-), we started to compare anxiety-like behavior and avoidance in male vs. female GAD65-/- mice and their wildtype littermates. In an open field, female GAD65-/- mice displayed increased activity, while male GAD65-/- mice showed an increased adaptation of anxiety-like behavior over time. GAD65-/- mice of both sexes had a higher preference for social interaction partners, which was further heightened in male mice. In male mice higher escape responses were observed during an active avoidance task. Together, female mice showed more stable emotional responses despite GAD65 deficiency. To gain insights into interneuron function in network structures controlling anxiety and threat perception, fast oscillations (10-45 Hz) were measured in ex vivo slice preparations of the anterior cingulate cortex (ACC). GAD65-/- mice of both sexes displayed increased gamma power in the ACC and a higher density of PV-positive interneurons, which are crucial for generating such rhythmic activity. In addition, GAD65-/- mice had lower numbers of somatostatin-positive interneurons in the basolateral amygdala and in the dorsal dentate gyrus especially in male mice, two key regions important for anxiety and active avoidance responses. Our data suggest sex differences in the configuration of GABAergic interneurons in a cortico-amygdala-hippocampal network controlling network activity patterns, anxiety and threat avoidance behavior.
Topics: Mice; Female; Male; Animals; Mice, Knockout; Glutamate Decarboxylase; Sex Characteristics; Anxiety; Anxiety Disorders; Interneurons; gamma-Aminobutyric Acid
PubMed: 37230180
DOI: 10.1016/j.nbd.2023.106165 -
Journal of Traumatic Stress Aug 2023Transdiagnostic treatments have been designed to target common processes for clusters of disorders. One such treatment, transdiagnostic behavior therapy (TBT), targets...
Transdiagnostic treatments have been designed to target common processes for clusters of disorders. One such treatment, transdiagnostic behavior therapy (TBT), targets avoidance across emotional disorders, including posttraumatic stress disorder (PTSD), depressive disorders, and anxiety disorders, and has demonstrated efficacy in randomized controlled trials. The current study was designed to examine whether distinct treatment trajectories would emerge in a sample of 112 veterans receiving TBT and whether diagnostic comorbidity, baseline levels of several transdiagnostic risk factors, or treatment engagement influence trajectory membership. Growth mixture modeling revealed three distinct trajectories across depression, ds = 0.55-1.09; PTSD ds = -0.07-1.43; and panic disorder symptoms, ds = -0.13-1.09. Notably, for PTSD and panic disorder symptoms, separate classes for responders and nonresponders emerged among participants with high baseline symptom levels. Findings for the risk factors suggested that PTSD and panic nonresponders evidenced significantly higher behavioral avoidance at baseline and reduced engagement in treatment procedures and homework completion compared to responders. Together, the findings provide additional support for the use of TBT in the treatment of emotional disorders, including PTSD. Potential adaptations are discussed for patients with significantly elevated behavioral avoidance to improve treatment engagement and related outcomes.
Topics: Humans; Stress Disorders, Post-Traumatic; Behavior Therapy; Mood Disorders; Veterans; Anxiety Disorders
PubMed: 37549108
DOI: 10.1002/jts.22963 -
Nature Communications Jul 2023Experiences have been shown to modulate behavior and physiology of future generations in some contexts, but there is limited evidence for inheritance of associative...
Experiences have been shown to modulate behavior and physiology of future generations in some contexts, but there is limited evidence for inheritance of associative memory in different species. Here, we trained C. elegans nematodes to associate an attractive odorant with stressful starvation conditions and revealed that this associative memory was transmitted to the F1 progeny who showed odor-evoked avoidance behavior. Moreover, the F1 and the F2 descendants of trained animals exhibited odor-evoked cellular stress responses, manifested by the translocation of DAF-16/FOXO to cells' nuclei. Sperm, but not oocytes, transmitted these odor-evoked cellular stress responses which involved H3K9 and H3K36 methylations, the small RNA pathway machinery, and intact neuropeptide secretion. Activation of a single chemosensory neuron sufficed to induce a serotonin-mediated systemic stress response in both the parental trained generation and in its progeny. Moreover, inheritance of the cellular stress responses increased survival chances of the progeny as exposure to the training odorant allowed the animals to prepare in advance for an impending adversity. These findings suggest that in C. elegans associative memories and cellular changes may be transferred across generations.
Topics: Animals; Male; Caenorhabditis elegans; Semen; Caenorhabditis elegans Proteins; Neuropeptides; Cell Nucleus
PubMed: 37454110
DOI: 10.1038/s41467-023-39804-8 -
Microbiome Sep 2023The influence of microbiota in ecological interactions, and in particular competition, is poorly known. We studied competition between two insect species, the invasive...
BACKGROUND
The influence of microbiota in ecological interactions, and in particular competition, is poorly known. We studied competition between two insect species, the invasive pest Drosophila suzukii and the model Drosophila melanogaster, whose larval ecological niches overlap in ripe, but not rotten, fruit.
RESULTS
We discovered D. suzukii females prevent costly interspecific larval competition by avoiding oviposition on substrates previously visited by D. melanogaster. More precisely, D. melanogaster association with gut bacteria of the genus Lactobacillus triggered D. suzukii avoidance. However, D. suzukii avoidance behavior is condition-dependent, and D. suzukii females that themselves carry D. melanogaster bacteria stop avoiding sites visited by D. melanogaster. The adaptive significance of avoiding cues from the competitor's microbiota was revealed by experimentally reproducing in-fruit larval competition: reduced survival of D. suzukii larvae only occurred if the competitor had its normal microbiota.
CONCLUSIONS
This study establishes microbiotas as potent mediators of interspecific competition and reveals a central role for context-dependent behaviors under bacterial influence. Video Abstract.
Topics: Female; Animals; Drosophila; Drosophila melanogaster; Fruit; Lactobacillus; Larva; Microbiota
PubMed: 37679800
DOI: 10.1186/s40168-023-01617-8 -
Current Biology : CB Aug 2023Pursuing prey through clutter is a complex and risky activity requiring integration of guidance subsystems for obstacle avoidance and target pursuit. The unobstructed...
Pursuing prey through clutter is a complex and risky activity requiring integration of guidance subsystems for obstacle avoidance and target pursuit. The unobstructed pursuit trajectories of Harris' hawks Parabuteo unicinctus are well modeled by a mixed guidance law feeding back target deviation angle and line-of-sight rate. Here we ask how their pursuit behavior is modified in response to obstacles, using high-speed motion capture to reconstruct flight trajectories recorded during obstructed pursuit of maneuvering targets. We find that Harris' hawks use the same mixed guidance law during obstructed pursuit but appear to superpose a discrete bias command that resets their flight direction to aim at a clearance of approximately one wing length from an upcoming obstacle as they reach some threshold distance from it. Combining a feedback command in response to target motion with a feedforward command in response to upcoming obstacles provides an effective means of prioritizing obstacle avoidance while remaining locked-on to a target. We therefore anticipate that a similar mechanism may be used in terrestrial and aquatic pursuit. The same biased guidance law could also be used for obstacle avoidance in drones designed to intercept other drones in clutter, or to navigate between fixed waypoints in urban environments.
Topics: Animals; Birds; Predatory Behavior
PubMed: 37421951
DOI: 10.1016/j.cub.2023.06.047