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The Journal of Neuroscience : the... Aug 2023To understand how the brain produces behavior, we must elucidate the relationships between neuronal connectivity and function. The medial prefrontal cortex (mPFC) is...
To understand how the brain produces behavior, we must elucidate the relationships between neuronal connectivity and function. The medial prefrontal cortex (mPFC) is critical for complex functions including decision-making and mood. mPFC projection neurons collateralize extensively, but the relationships between mPFC neuronal activity and brain-wide connectivity are poorly understood. We performed whole-brain connectivity mapping and fiber photometry to better understand the mPFC circuits that control threat avoidance in male and female mice. Using tissue clearing and light sheet fluorescence microscopy (LSFM), we mapped the brain-wide axon collaterals of populations of mPFC neurons that project to nucleus accumbens (NAc), ventral tegmental area (VTA), or contralateral mPFC (cmPFC). We present DeepTraCE (deep learning-based tracing with combined enhancement), for quantifying bulk-labeled axonal projections in images of cleared tissue, and DeepCOUNT (deep-learning based counting of objects via 3D U-net pixel tagging), for quantifying cell bodies. Anatomical maps produced with DeepTraCE aligned with known axonal projection patterns and revealed class-specific topographic projections within regions. Using TRAP2 mice and DeepCOUNT, we analyzed whole-brain functional connectivity underlying threat avoidance. PL was the most highly connected node with functional connections to subsets of PL-cPL, PL-NAc, and PL-VTA target sites. Using fiber photometry, we found that during threat avoidance, cmPFC and NAc-projectors encoded conditioned stimuli, but only when action was required to avoid threats. mPFC-VTA neurons encoded learned but not innate avoidance behaviors. Together our results present new and optimized approaches for quantitative whole-brain analysis and indicate that anatomically defined classes of mPFC neurons have specialized roles in threat avoidance. Understanding how the brain produces complex behaviors requires detailed knowledge of the relationships between neuronal connectivity and function. The medial prefrontal cortex (mPFC) plays a key role in learning, mood, and decision-making, including evaluating and responding to threats. mPFC dysfunction is strongly linked to fear, anxiety and mood disorders. Although mPFC circuits are clear therapeutic targets, gaps in our understanding of how they produce cognitive and emotional behaviors prevent us from designing effective interventions. To address this, we developed a high-throughput analysis pipeline for quantifying bulk-labeled fluorescent axons [DeepTraCE (deep learning-based tracing with combined enhancement)] or cell bodies [DeepCOUNT (deep-learning based counting of objects via 3D U-net pixel tagging)] in intact cleared brains. Using DeepTraCE, DeepCOUNT, and fiber photometry, we performed detailed anatomic and functional mapping of mPFC neuronal classes, identifying specialized roles in threat avoidance.
Topics: Mice; Male; Female; Animals; Neural Pathways; Brain; Neurons; Prefrontal Cortex; Nucleus Accumbens
PubMed: 37491314
DOI: 10.1523/JNEUROSCI.0697-23.2023 -
Cell Reports Oct 2023Animals rapidly acquire surrounding information to perform the appropriate behavior. Although social learning is more efficient and accessible than self-learning for...
Animals rapidly acquire surrounding information to perform the appropriate behavior. Although social learning is more efficient and accessible than self-learning for animals, the detailed regulatory mechanism of social learning remains unknown, mainly because of the complicated information transfer between animals, especially for aversive conditioning information transmission. The current study revealed that, during social learning, the neural circuit in observer flies used to process acquired aversive conditioning information from demonstrator flies differs from the circuit used for self-learned classic aversive conditioning. This aversive information transfer is species dependent. Solitary flies cannot learn this information through social learning, suggesting that this ability is not an innate behavior. Neurons used to process and execute avoidance behavior to escape from electrically shocked flies are all in the same brain region, indicating that the fly brain has a common center for integrating external stimuli with internal states to generate flight behavior.
Topics: Animals; Drosophila; Drosophila melanogaster; Conditioning, Psychological; Avoidance Learning; Neurons
PubMed: 37782557
DOI: 10.1016/j.celrep.2023.113207 -
Translational Neuroscience Jan 2023Apolipoprotein E (ApoE) is associated with Alzheimer's disease (AD) and cognitive dysfunction in elderly individuals. There have been extensive studies on behavioral...
BACKGROUND
Apolipoprotein E (ApoE) is associated with Alzheimer's disease (AD) and cognitive dysfunction in elderly individuals. There have been extensive studies on behavioral abnormalities in ApoE-deficient (Apoe) mice, which have been described as AD mouse models. Spontaneously hyperlipidemic mice were discovered in 1999 as ApoE-deficient mice due to ApoE gene mutations. However, behavioral abnormalities in commercially available Apoe mice remain unclear. Accordingly, we aimed to investigate the behavioral abnormalities of Apoe mice.
RESULTS
Apoe mice showed decreased motor skill learning and increased anxiety-like behavior toward heights. Apoe mice did not show abnormal behavior in the Y-maze test, open-field test, light/dark transition test, and passive avoidance test.
CONCLUSION
Our findings suggest the utility of Apoe mice in investigating the function of ApoE in the central nervous system.
PubMed: 37396111
DOI: 10.1515/tnsci-2022-0284 -
Plants (Basel, Switzerland) Jan 2024Florivory, i.e., flower herbivory, of various types is common and can strongly reduce plant fitness. Flowers suffer two very different types of herbivory: (1) the... (Review)
Review
Florivory, i.e., flower herbivory, of various types is common and can strongly reduce plant fitness. Flowers suffer two very different types of herbivory: (1) the classic herbivory of consuming tissues and (2) nectar theft. Unlike the non-reversibility of consumed tissues, nectar theft, while potentially reducing a plant's fitness by lowering its attraction to pollinators, can, in various cases, be fixed quickly by the production of additional nectar. Therefore, various mechanisms to avoid or reduce florivory have evolved. Here, I focus on one of the flowers' defensive mechanisms, aposematism, i.e., warning signaling to avoid or at least reduce herbivory via the repelling of herbivores. While plant aposematism of various types was almost ignored until the year 2000, it is a common anti-herbivory defense mechanism in many plant taxa, operating visually, olfactorily, and, in the case of nectar, via a bitter taste. Flower aposematism has received only very little focused attention as such, and many of the relevant publications that actually demonstrated herbivore repellence and avoidance learning following flower signaling did not refer to repellence as aposematism. Here, I review what is known concerning visual-, olfactory-, and nectar-taste-based flower aposematism, including some relevant cases of mimicry, and suggest some lines for future research.
PubMed: 38337924
DOI: 10.3390/plants13030391 -
Psychopharmacology Aug 2023Balancing approach of positive and avoidance of negative stimuli is essential when faced with approach-avoidance conflicts, e.g., situations with both positive and... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE
Balancing approach of positive and avoidance of negative stimuli is essential when faced with approach-avoidance conflicts, e.g., situations with both positive and negative outcomes. This balance is disturbed in several mental disorders, e.g., excessive avoidance in anxiety disorders, and heightened approach in substance use disorders. Since stress is assumed to impact these disorders' etiology and maintenance, it seems crucial to understand how stress influences behavior in approach-avoidance conflicts. Indeed, some studies suggested altered approach-avoidance behavior under acute stress, but the mechanism underlying these effects is unknown.
OBJECTIVES
Investigate how the pharmacological manipulation of major stress mediators (cortisol and noradrenaline) influences task-based approach-avoidance conflict behavior in healthy individuals.
METHODS
Ninety-six participants (48 women, 48 men) received either 20mg hydrocortisone, 20mg yohimbine, both, or placebo before performing a task targeting foraging under predation in a fully crossed double-blind between-subject design. Moreover, we investigated effects of gender and endogenous testosterone and estradiol levels on approach-avoidance behavior.
RESULTS
While biological stress markers (cortisol concentration, alpha amylase activity) indicated successful pharmacological manipulation, behavior in approach-avoidance conflicts was not affected as expected. Although yohimbine administration affected risky foraging latency under predation, we found no main effect of hydrocortisone or their interaction on behavior. In contrast, we found gender differences for almost all behavioral outcome measures, which might be explained by differences in endogenous testosterone levels.
CONCLUSIONS
The investigated major stress mediators were not sufficient to imitate previously shown stress effects on approach-avoidance conflict behavior. We discuss potential reasons for our findings and implications for future research.
Topics: Male; Humans; Female; Hydrocortisone; Yohimbine; Anxiety Disorders; Testosterone
PubMed: 37314480
DOI: 10.1007/s00213-023-06396-6 -
Cell Reports Apr 2024Pathogenic infection elicits behaviors that promote recovery and survival of the host. After exposure to the pathogenic bacterium Pseudomonas aeruginosa PA14, the...
Pathogenic infection elicits behaviors that promote recovery and survival of the host. After exposure to the pathogenic bacterium Pseudomonas aeruginosa PA14, the nematode Caenorhabditis elegans modifies its sensory preferences to avoid the pathogen. Here, we identify antagonistic neuromodulators that shape this acquired avoidance behavior. Using an unbiased cell-directed neuropeptide screen, we show that AVK neurons upregulate and release RF/RYamide FLP-1 neuropeptides during infection to drive pathogen avoidance. Manipulations that increase or decrease AVK activity accelerate or delay pathogen avoidance, respectively, implicating AVK in the dynamics of avoidance behavior. FLP-1 neuropeptides drive pathogen avoidance through the G protein-coupled receptor DMSR-7, as well as other receptors. DMSR-7 in turn acts in multiple neurons, including tyraminergic/octopaminergic neurons that receive convergent avoidance signals from the cytokine DAF-7/transforming growth factor β. Neuromodulators shape pathogen avoidance through multiple mechanisms and targets, in agreement with the distributed neuromodulatory connectome of C. elegans.
Topics: Animals; Caenorhabditis elegans; Neuropeptides; Pseudomonas aeruginosa; Caenorhabditis elegans Proteins; Biogenic Monoamines; Neurons; Avoidance Learning; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 38573858
DOI: 10.1016/j.celrep.2024.114042 -
Health Science Reports Jul 2023Willingness to engage in preventive behaviors against coronavirus disease 2019 (COVID-19) depends on people's risk perception. This is especially important in cancer...
BACKGROUND AND AIMS
Willingness to engage in preventive behaviors against coronavirus disease 2019 (COVID-19) depends on people's risk perception. This is especially important in cancer patients who are at risk of complications from the disease. Therefore, this study was conducted to investigate avoidance of COVID-19 preventive behavior of in cancer patients.
METHODS
This cross-sectional analytical study was done with 200 cancer patients who were selected by convenience sampling method. The study was conducted in Imam Khomeini Hospital of Ardabil, Iran from July to August 2020. A researcher-made questionnaire was used to investigate the risk perception of cancer patients towards COVID-19 with seven subscales according to the Extended Parallel Process Model. Data were analyzed by SPSS 20 using Pearson correlation and linear regression tests.
RESULTS
The mean and standard deviation of the age of 200 participants (including 109 men and 91 women) was 48 ± 17. Results showed that the response efficacy (12.6 ± 2.2) had the highest mean and defensive avoidance (8 ± 2.8) had the lowest mean score among EPPM constructs. Linear regression results showed that fear ( = 0.242, > 0.001), and perceived severity ( = 0.191, = 0.008) were significant predictors of defensive avoidance.
CONCLUSION
Perceived severity and fear were significant predictors of defensive avoidance, and providing accurate and reliable news and information can be effective in reducing fear and promoting preventive behaviors.
PubMed: 37431485
DOI: 10.1002/hsr2.1401 -
Archives of Dermatological Research Aug 2023Individuals can reduce the risk of developing skin cancer by minimizing ultraviolet sunlight exposure, though recent trends in sun-protective behaviors remain to be...
Individuals can reduce the risk of developing skin cancer by minimizing ultraviolet sunlight exposure, though recent trends in sun-protective behaviors remain to be investigated. To evaluate sun-protective behaviors and sunburn among US adults. We analyzed data from the 2010, 2015, and 2020 National Health Interview Survey (NHIS), an annual, cross-sectional survey conducted by the US Census Bureau. Multivariable regression models were stratified by demographic variables and constructed to evaluate sun-protective behaviors and sunburn avoidance across time. From 2010 through 2020, US adults had significantly increased prevalence of seeking shade (p value, 0.003), wearing wide-brimmed hats (< 0.001), wearing long-sleeved shirts (< 0.001), using sunscreen (< 0.001), and avoiding sunburns (< 0.001) and significantly decreased prevalence of sun avoidance (< 0.001). Disparities in sun-protective behaviors also exist among different sexes, ages, education levels, and those reporting higher sun sensitivity. This cross-sectional study found that by 2020, US adults had an increased prevalence of wearing sun-protective clothing and sunscreen use, though decreased prevalence of sun avoidance. Although certain sun-protective behaviors have become more prevalent, the incidence of skin cancer continues to rise. Efforts to understand drivers of sun-protective behaviors and targeted intervention efforts are needed.
Topics: Humans; Adult; Sunburn; Sunscreening Agents; Cross-Sectional Studies; Health Behavior; Skin Neoplasms
PubMed: 36790452
DOI: 10.1007/s00403-023-02547-z -
Journal of Eating Disorders Jul 2023Having suffered from longstanding anorexia nervosa (AN) for more than a decade, and after meeting many patients who have also been labelled as 'treatment-resistant',...
Having suffered from longstanding anorexia nervosa (AN) for more than a decade, and after meeting many patients who have also been labelled as 'treatment-resistant', 'treatment-refractory', or similar terms, I feel a strong responsibility to express my deep fears and sadness about the more harmful new label of 'terminal anorexia'. This article is based on a reflective and private email that I emotionally wrote in Autumn 2022, soon after reading a thought-provoking paper (Guarda et al. in J Eat Disord 10:79, 2022) about the new term. When I wrote the email, I had not read the Gaudiani et al. (J Eat Disord 10:23, 2022) paper that proposed clinical characteristics for the new diagnosis. Hence, my email was not, and this article is not, a response to Gaudiani et al. (2022). Challenging the criteria that they proposed is beyond the scope of this article, which is just a lived experience reaction to the concept of 'terminal anorexia' (regardless of who created it and who tries to define it).Before learning about 'terminal anorexia' in 2022, I assumed that 'unconditional positive regard' included mental health professionals' unconditional hope for their patients' ability to live meaningful lives, irrespective of how severe or chronic their patients' conditions were. Therefore, I was very disheartened when the label 'terminal anorexia' was circulated by professionals. Research is not just read, seen, and heard about by the professionals who promote it. Vulnerable and conflicted eating disorder (ED) sufferers, and their families, can be victims of theoretical academic discourse that has real-world, life-or-death implications.The purpose of my article is not to suppress the arbitrary new term, which is sadly already commonly used in clinical practice and amongst very young ED sufferers, despite it having no agreed definition. I intend to outline some of the reasons why I believe that the term (not its hypothesised criteria, which are beyond the scope of my article) is harming ED sufferers, so that these harms can be addressed before it is too late. I have grouped these reasons into six key themes that inevitably overlap and cannot be perfectly separated. They are: [1] Hope and identity destruction; [2] Avoidance and collusion; [3] Self-diagnosis and misdiagnosis; [4] Comparisons; [5] Dangerous precedents; [6] Current and future treatments.
PubMed: 37400874
DOI: 10.1186/s40337-023-00823-x -
Nature Communications Jul 2023Locomotor activities can enhance learning, but the underlying circuit and synaptic mechanisms are largely unknown. Here we show that locomotion facilitates aversive...
Locomotor activities can enhance learning, but the underlying circuit and synaptic mechanisms are largely unknown. Here we show that locomotion facilitates aversive olfactory learning in C. elegans by activating mechanoreceptors in motor neurons, and transmitting the proprioceptive information thus generated to locomotion interneurons through antidromic-rectifying gap junctions. The proprioceptive information serves to regulate experience-dependent activities and functional coupling of interneurons that process olfactory sensory information to produce the learning behavior. Genetic destruction of either the mechanoreceptors in motor neurons, the rectifying gap junctions between the motor neurons and locomotion interneurons, or specific inhibitory synapses among the interneurons impairs the aversive olfactory learning. We have thus uncovered an unexpected role of proprioception in a specific learning behavior as well as the circuit, synaptic, and gene bases for this function.
Topics: Animals; Caenorhabditis elegans; Gap Junctions; Interneurons; Proprioception; Avoidance Learning; Locomotion
PubMed: 37500635
DOI: 10.1038/s41467-023-40286-x