Behavioural and dopaminergic signatures of resilience

Willmore, Lindsay; Cameron, Courtney M.; Yang, John; Witten, Ilana B.; Falkner, Annegret L.

doi:10.1038/s41586-022-05328-2

Cited by 63 publications

(43 citation statements)

References 63 publications

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“…Neuro-behaviors such as depression, anxiety, cognition, and learning are highly associated with neurotransmitters. , A significant decrease in GABA has been observed in abnormal neural conditions, including depression and autism spectrum disorder. , Serotonin deficits are implicated in the pathogenesis of depression, impulsivity, and suicidal ideations . In this work, correlation analysis of affected indicators showed that the reduced activity of zebrafish larvae after exposure to bisphenol analogues was related to decreased neurotransmitter levels.…”

Section: Discussionmentioning

confidence: 64%

“…Neuro-behaviors such as depression, anxiety, cognition, and learning are highly associated with neurotransmitters. 57,58 A significant decrease in GABA has been observed in abnormal neural conditions, including depression and autism spectrum disorder. 59,60 Serotonin deficits are implicated in the pathogenesis of depression, impulsivity, and suicidal ideations.…”

Section: Bisphenol Analogues Affected Zebrafish Neuro-behavior By Int...mentioning

confidence: 99%

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Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut–Brain Regulation in Zebrafish

Mu,

Liu,

Zhao

et al. 2024

Environ. Sci. Technol.

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There is epidemiological evidence in humans that exposure to endocrine-disrupting chemicals such as bisphenol A (BPA) is tied to abnormal neuroendocrine function with both behavioral and intestinal symptoms. However, the underlying mechanism of this effect, particularly the role of gut−brain regulation, is poorly understood. We exposed zebrafish embryos to a concentration series (including environmentally relevant levels) of BPA and its analogues. The analogue bisphenol G (BPG) yielded the strongest behavioral impact on zebrafish larvae and inhibited the largest number of neurotransmitters, with an effective concentration of 0.5 μg/L, followed by bisphenol AF (BPAF) and BPA. In neurod1:EGFP transgenic zebrafish, BPG and BPAF inhibited the distribution of enteroendocrine cells (EECs), which is associated with decreased neurotransmitters level and behavioral activity. Immune staining of ace-α-tubulin suggested that BPAF inhibited vagal neural development at 50 and 500 μg/L. Single-cell RNA-Seq demonstrated that BPG disrupted the neuroendocrine system by inducing inflammatory responses in intestinal epithelial cells via TNFα-trypsin-EEC signaling. BPAF exposure activated apoptosis and inhibited neural developmental pathways in vagal neurons, consistent with immunofluorescence imaging studies. These findings show that both BPG and BPAF affect the neuroendocrine system through the gut−brain axis but by different mechanisms, revealing new insights into the modes of bisphenol-mediated neuroendocrine disruption.

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Section: Discussionmentioning

confidence: 64%

Section: Bisphenol Analogues Affected Zebrafish Neuro-behavior By Int...mentioning

confidence: 99%

Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut–Brain Regulation in Zebrafish

Mu,

Liu,

Zhao

et al. 2024

Environ. Sci. Technol.

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“…While our imaging findings include both males and females, and female ELS-exposed mice appear to respond to CNSDS by reduced open field center time, there was no effect of NAc ensemble inhibition on female behavior across three tests. Recent work using machine learning-based behavioral analysis of female behavior during social defeat attacks also shows relatively more subtle behavioral responses to defeat compared to males (Willmore et al, 2022). Additional research is needed to determine whether distinct adult stressors would produce a more robust effect, and whether other brain regions not assessed in the current study such as within the hypothalamus more robustly encode female cellular memory of ELS.…”

Section: Discussionmentioning

confidence: 99%

Reactivation of early-life stress-sensitive neuronal ensembles contributes to lifelong stress hypersensitivity

Balouek

Mclain

Minerva

et al. 2022

Preprint

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Early-life stress (ELS) is one of the strongest lifetime risk factors for depression, anxiety, suicide, and other psychiatric disorders, particularly after facing additional stressful events later in life. Human and animal studies demonstrate that ELS sensitizes individuals to subsequent stress. However, the neurobiological basis of such stress sensitization remains largely unexplored. We hypothesized that ELS-induced stress sensitization would be detectable at the level of neuronal ensembles, such that cells activated by ELS would be more reactive to adult stress. To test this, we leveraged transgenic mice to genetically tag, track, and manipulate experience-activated neurons. We found that in both male and female mice, ELS-activated neurons within the nucleus accumbens (NAc), and to a lesser-extent the medial prefrontal cortex, were preferentially reactivated by adult stress. To test whether reactivation of ELS-activated ensembles in the NAc contributes to stress hypersensitivity, we expressed hM4Dis receptor in control or ELS-activated neurons of pups and chemogenetically inhibited their activity during experience of adult stress. Inhibition of ELS-activated NAc neurons, but not control-tagged neurons, ameliorated social avoidance behavior following chronic social defeat stress in males. These data provide evidence that ELS-induced stress hypersensitivity is encoded at the level of corticolimbic neuronal ensembles.

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“…Stress-induced modulation of volitional social motivation in male and female mice. Stress resilience and susceptibility in rodents are associated with neurophysiological changes in the mesolimbic dopaminergic system [48][49][50][51][52][53] . However, this mechanistic understanding is constrained by two pragmatic procedural considerations.…”

Section: Discussionmentioning

confidence: 99%

Individual differences in volitional social motivation in male and female mice following social stress

Navarrete

Schneider

Smith

et al. 2022

Preprint

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Background: A key challenge in developing new treatments for neuropsychiatric illness is the disconnect between preclinical models and the complexity of human social behavior. We aimed to integrate voluntary social self-administration into a preclinical rodent stress model, as a platform for the identification of basic brain and behavior mechanisms underlying stress-induced individual differences in social motivation. Here, we introduce an operant social stress (OSS) procedure with male and female mice, where lever presses are reinforced by freely moving social interaction with a familiar social partner across social stress exposure. Methods: OSS is composed of three phases: (i) social self-administration training, (ii) social stress concurrent with daily reinforced social self-administration testing, and (iii) post-stress operant social reward testing under both non-reinforced and reinforced conditions. We resolve social stress-induced changes to social motivation behaviors using hierarchical clustering and aggregated z-scores, capturing the spectrum of individual differences that we describe with a social index score. Results: OSS captures a range of stress-related dynamic social motivation behaviors inclusive of sex as a biological variable. Both male and female mice lever press for access to a social partner, independent of social partner coat color or familiarity. Social stress attenuates social self-administration in males and promotes social reward seeking behavior in females. Hierarchical clustering does not adequately describe the relative distributions of social motivation following stress, which we find is better described as a non-binary behavioral distribution that we define by introducing the social index score. This index is stable across individual mice. Conclusion: We demonstrate that OSS can be used to detect stable individual differences in stress-induced changes to social motivation in male and female mice. These differences may reflect unique neurobiological, cellular and circuit mechanisms not captured by preclinical models that omit voluntary social behaviors. The inclusion of volitional social procedures may enhance the understanding of behavioral adaptations promoting stress resiliency and their mechanisms under more naturalistic conditions.

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Behavioural and dopaminergic signatures of resilience

Cited by 63 publications

References 63 publications

Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut–Brain Regulation in Zebrafish

Bisphenol A Analogues Induce Neuroendocrine Disruption via Gut–Brain Regulation in Zebrafish

Reactivation of early-life stress-sensitive neuronal ensembles contributes to lifelong stress hypersensitivity

Individual differences in volitional social motivation in male and female mice following social stress

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