The Avian Hippocampal Formation and the Stress Response

Smulders, Tom V.

doi:10.1159/000477654

Cited by 67 publications

(57 citation statements)

References 87 publications

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“…Negative feedback is coordinated by GR and MR in the hypothalamus, hippocampus and pituitary gland (de Kloet et al, 1998;Smulders, 2017), and differential expression of these receptors has been associated with changes in negative feedback efficacy (de Kloet et al, 1998;Zimmer & Spencer, 2014). As it seems likely that the differences in hormonal profiles covary with differences in receptor numbers, measuring receptor expression is an important future direction.…”

Section: Endocrine Predictors Of Stress Resiliencementioning

confidence: 99%

“…In this case, the significant interaction with stress-induced corticosterone could be simply an artifact of this measure being positively correlated with the strength of negative feedback. The acute stress response and negative feedback may be functionally linked, as negative feedback is induced by corticosterone binding to GR, and to a lesser extent toMR (de Kloet, Vreugdenhil, Oitzl, & Joëls, 1998;Smulders, 2017). Consequently,…”

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confidence: 99%

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On again, off again: Acute stress response and negative feedback together predict resilience to experimental challenges

et al. 2019

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Individuals often vary markedly in their ability to cope with stressors, but the drivers of this variation remain poorly understood. Many studies have tested relationships among individual variation in glucocorticoid levels and the response to challenges—often finding inconsistent patterns; however, few have addressed whether variation in the capacity to terminate the stress response through negative feedback is associated with stress resilience. While conceptual models predict that interactions among different components of hypothalamic–pituitary–adrenal (HPA) axis regulation may be important predictors of the phenotypic and fitness effects of stress, we are aware of no previous experimental tests of this hypothesis. We investigate whether individual variation in HPA axis regulation is related to resilience to experimental challenges in free‐living tree swallows (Tachycineta bicolor). We mimicked salient natural challenges by temporarily reducing flight efficiency or increasing perceived predation risk during incubation, and determined whether HPA axis responsiveness prior to treatments predicted resilience. Females that exhibited both a robust HPA axis activation and strong negative feedback were less likely to abandon nests during incubation. Our results suggest that exhibiting a strong HPA axis activation coupled with effective negative feedback may predict stress resilience. Therefore, the ability to turn on and then off the HPA axis efficiently may be important for fitness. Our results also suggest that the interactions between different components of the HPA axis may provide greater insight into differences in stress coping capacity. A plain language summary is available for this article.

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Section: Endocrine Predictors Of Stress Resiliencementioning

confidence: 99%

mentioning

confidence: 99%

On again, off again: Acute stress response and negative feedback together predict resilience to experimental challenges

et al. 2019

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“…Biological sex manifests in various distinct physiological phenotypes, particularly concerning those associated with reproductive processes [81][82][83][84]. However, an organism's response to a stressor, no matter the sex, can trigger the mobilization of internal bodily resources to promote its survival [85][86][87][88]. Thus, an active sex-specific physiologically-driven alternative splicing landscape under stress may become reconciled in the HPG axis to shunt focus to other biological processes to support survival.…”

Section: Resource Redirection Hypothesismentioning

confidence: 99%

Stress-mediated convergence of splicing landscapes in male and female rock doves

et al. 2020

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Background: The process of alternative splicing provides a unique mechanism by which eukaryotes are able to produce numerous protein products from the same gene. Heightened variability in the proteome has been thought to potentiate increased behavioral complexity and response flexibility to environmental stimuli, thus contributing to more refined traits on which natural and sexual selection can act. While it has been long known that various forms of environmental stress can negatively affect sexual behavior and reproduction, we know little of how stress can affect the alternative splicing associated with these events, and less still about how splicing may differ between sexes. Using the model of the rock dove (Columba livia), our team previously uncovered sexual dimorphism in the basal and stress-responsive gene transcription of a biological system necessary for facilitating sexual behavior and reproduction, the hypothalamic-pituitary-gonadal (HPG) axis. In this study, we delve further into understanding the mechanistic underpinnings of how changes in the environment can affect reproduction by testing the alternative splicing response of the HPG axis to an external stressor in both sexes. Results: This study reveals dramatic baseline differences in HPG alternative splicing between males and females. However, after subjecting subjects to a restraint stress paradigm, we found a significant reduction in these differences between the sexes. In both stress and control treatments, we identified a higher incidence of splicing activity in the pituitary in both sexes as compared to other tissues. Of these splicing events, the core exon event is the most abundant form of splicing and more frequently occurs in the coding regions of the gene. Overall, we observed less splicing activity in the 3'UTR (untranslated region) end of transcripts than the 5'UTR or coding regions. Conclusions: Our results provide vital new insight into sex-specific aspects of the stress response on the HPG axis at an unprecedented proximate level. Males and females uniquely respond to stress, yet exhibit splicing patterns suggesting a convergent, optimal splicing landscape for stress response. This information has the potential to inform evolutionary theory as well as the development of highly-specific drug targets for stressinduced reproductive dysfunction.

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“…A second hypothesis to explain the presence of decreased alternative splicing differences between stressed males and females relative to controls is that the stress response redirects resources from less essential biological processes, like reproduction, 680 to those more necessary for survival. Biological sex manifests in various distinct physiological phenotypes, particularly concerning those associated with reproductive processes (Ngun et al, 2011;Arnold & Itoh, 2011;Bundy, Vied & Nowakowski, 2017;Lee, 2018)However, an organism's response to a stressor, no matter the sex, can trigger the mobilization of internal bodily resources to promote its survival (Wendelaar 685 Bonga, 1997;Goldstein, 2010;Nicolaides et al, 2015;Smulders, 2017). Thus, an active sex-specific physiologically-driven alternative splicing landscape under stress may become reconciled in the HPG axis to shunt focus to other biological processes to support survival.…”

Section: Resource Redirection Hypothesismentioning

confidence: 99%

Stress-mediated convergence of splicing landscapes in male and female Rock Doves

Lang

MacManes

Calisi

et al. 2019

Preprint

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Background: The process of alternative splicing provides a unique mechanism by which eukaryotes are able to produce numerous protein products from the same gene. Heightened variability in the proteome has been thought to potentiate increased behavioral complexity and response flexibility to environmental stimuli, thus contributing to more refined traits on which natural and sexual selection can act. While it has been long known that various forms of environmental stress can negatively affect sexual behavior and reproduction, we know little of how stress can affect the alternative splicing associated with these events, and less still about how splicing may differ between sexes. Using the model of the rock dove (Columba livia), our team previously uncovered sexual dimorphism in the basal and stress-responsive gene transcription of a biological system necessary for facilitating sexual behavior and reproduction, the hypothlamic-pituitary-gonadal (HPG) axis. In this study, we delve further into understanding the mechanistic underpinnings of how changes in the environment can affect reproduction by testing the alternative splicing response of the HPG axis to an external stressor in both sexes.Results: This study reveals dramatic baseline differences in HPG alternative splicing between males and females. However, post submitting subjects to a restraint stress paradigm, we found a significant reduction in these differences between the sexes. In both stress and control treatments, we identified a higher incidence of splicing activity in the pituitary in both sexes as compared to other tissues. Of these splicing events, the core exon event is the most abundant form of splicing and more frequently occurs in the coding regions of the gene. Overall, we observed less splicing activity in the 3'UTR end of transcripts than the 5'UTR or coding regions. Conclusions:Our results provide vital new insight into sex-specific aspects of the stress response on the HPG axis at an unprecedented proximate level. Males and females uniquely respond to stress, yet exhibit splicing patterns suggesting a convergent, optimal splicing landscape for stress response. This information has the potential to inform evolutionary theory as well as the development of highly-specific drug targets for stress-induced reproductive dysfunction.

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The Avian Hippocampal Formation and the Stress Response

Cited by 67 publications

References 87 publications

On again, off again: Acute stress response and negative feedback together predict resilience to experimental challenges

On again, off again: Acute stress response and negative feedback together predict resilience to experimental challenges

Stress-mediated convergence of splicing landscapes in male and female rock doves

Stress-mediated convergence of splicing landscapes in male and female Rock Doves

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