Biology subjects

Wong, R. Y.

Publications and source records attributed to Wong, R. Y..

13 recordsLinked to original sources

bioRxiv2026

Differences in interactions between brain regions across personality types while learning in zebrafish (Danio rerio)

Learning is an important process for survival. Many studies find that variation in learning ability is related to personality type. Bold individuals generally learn faster than shy, however, the underlying neural mechanisms are not well understood. Potential mechanisms for differences in learning speed are variation in neurotransmitter activity, specifically dopamine and serotonin, and functional connectivity across the brain. In this study we quantified the number of generally active, active dopaminergic, and active serotonergic neurons using immunohistochemistry across 12 brain regions at two timepoints in bold and shy zebrafish undergoing an associative learning task. There were no interactions between treatment and personality type in any of the cell count measures suggesting that individual region activity and neurotransmitter activity do not explain learning differences. However, analyses of general neural activity networks revealed that the connection from the posterior zone of the dorsal telencephalon (olfactory cortex homolog) to lateral zone of the dorsal telencephalon (hippocampus homolog) was positive in bold but negative in shy fish undergoing learning. Overall, the results suggest that differences in activity involving reward processing in the brain may explain differences in reward learning between personality types.

neuroscience↗

bioRxiv2026

Personality Variation in Associative Learning and Memory Retention in Zebrafish (Danio rerio)

Animals differ in how they acquire and retain information, and modify their behavior while interacting with their environment. These differences have been linked to personality type, yet how personality type and sex influence reward-associated memory is not well understood. We investigated the effects of personality type, sex, days of conditioning, and food reward on learning and memory retention in zebrafish using the conditioned place preference paradigm. We conditioned zebrafish to associate a visual background with a food reward across eleven sessions and assessed memory recall seven days later by measuring duration, frequency of entry, and latency to first entry in the conditioned zone. We observed that bold fish had early conditioned zone engagement, whereas shy zebrafish gradually increased their behavior into the conditioned zone with repeated conditioning. With food reward, preference for the conditioned zone increased after 7 and 11 days post-conditioning relative to baseline. Seven days after the last conditioning with food reward, the preference for conditioned zone remained unchanged in shy fish. This suggests that shy fish retain the ability to recall the learned association for at least 7 days after conditioning. Overall, personality, food reward, and sex influence behavioral changes in food reward-associated cognition, with shy-treated males showing gradual increases in behavior into the conditioned zone. These findings suggest that personality and sex differences may depend on the nature and valence of the associative task to recall. Thus, this study emphasizes the importance of assessing memory retention alongside learning acquisition to understand the relationship between personality types and cognition.

animal behavior and cognition↗

bioRxiv2026

Antioxidant modulation of stress behavior depends on stress coping style: a role for N-acetylcysteine amide

Animals experience stressors in a variety of contexts that result in activation of neuroendocrine and cellular stress responses. Release of stress hormones can disrupt or restore redox homeostasis, and the resulting changes in oxidative states, physiology and behavior vary by an individuals stress coping style. However, oxidative stress can also directly modulate neuroendocrine stress signaling. To what extent individual differences in brain antioxidant levels alter behavioral stress levels is not well understood. The present study investigated how N-acetylcysteine amide (NACA), an antioxidant and glutamate-modulating compound, regulates stress behavior across zebrafish (Danio rerio) with different stress coping styles (proactive, reactive). Following 24-hour exposure to NACA or control conditions, we quantified individual and composite stress behaviors using a Light-Dark Test (LDT). As expected, both proactive fish and NACA-treated fish showed significantly lower stress behaviors compared to reactive and control animals, respectively. Notably, stress-reducing effects of NACA were only seen in those with a reactive stress coping style. Overall, our data suggest that antioxidant mechanisms (e.g., glutathione system) may be key in facilitating the distinct behavioral and physiological responses to stressors that characterize alternative stress coping styles. The results underscore how individual differences in stress coping style and redox state can influence behavioral responses to stress.

animal behavior and cognition↗

bioRxiv2026

Neuroendocrine Stress Induces Differential Oxidative Stress and Antioxidant Profiles between Proactive and Reactive Stress Coping Styles

Neuroendocrine stressors can disrupt the brains redox equilibrium by generating high levels of reactive oxygen species (ROS) that lead to oxidative stress. The magnitude of the effect of neuroendocrine stressors on brain redox equilibrium can be influenced by many internal and external factors. To what extent the relationship between neuroendocrine and oxidative stress is modulated by an individuals stress coping style is only beginning to be understood. To explore this, we subjected proactive and reactive zebrafish to an acute novelty stressor and subsequently quantified changes in behavior and whole brain biomarkers of oxidative stress and antioxidants (DNA damage, total glutathione (GSH), glutathione ratio, oxygen radical absorbance capacity (ORAC), and superoxide dismutase (SOD). Stressed fish had significantly higher total glutathione, trends higher ORAC, DNA damage, and glutathione ratio, and trend for lower SOD levels compared to controls. In addition, individuals with a reactive stress coping style exhibited significantly higher levels of SOD and glutathione ratio, and a trend for ORAC compared to proactive individuals. From a principal component analysis, we also found that the reactive individuals had significantly higher PC1 scores (antioxidant axis) compared to the proactive, and a trend for stressed fish having higher PC1 scores than control. The oxidative stress axis (PC2) showed that the stressed fish had a significantly higher PC2 score relative to control fish. Our results show that neuroendocrine stress-induced disruption of redox equilibrium in the brain differs by stress coping style. Those with a reactive stress coping style have elevated antioxidant capabilities and capacities. Overall, our findings suggest that elevated reactivity to neuroendocrine stressors commonly seen in reactive stress coping styles may be mitigated through the glutathione buffering system and other antioxidants.

animal behavior and cognition↗

bioRxiv2026

Differential adenosine signaling and effects of acute caffeine exposure on alternative stress coping styles in zebrafish (Danio rerio)

Changes within neurotransmitter systems are associated with variation in anxiety-related behavior. The adenosine signaling pathway has been associated with anxiety and caffeine has been utilized as a modulator. However, studies have not considered the impact of an individuals stress coping style (e.g. proactive, reactive) and corresponding differences in neuromolecular signaling that can influence the behavioral responses. To assess the role of adenosine signaling, we acutely treated reactive and proactive zebrafish with 50 mg/L caffeine and evaluated anxiety-like behavior using a novel tank diving test (NTDT). We then quantified whole-brain gene expression of genes representing distinct parts of the adenosine signaling pathway: adenosine receptors A1B, A2Aa, A2Ab, and A2B (adora1b, adora2aa, adora2ab, and adora2b, respectively) and enzymes adenosine deaminase (ada) and ecto-5-nucleotidase (nt5e). We found significant main effects of coping style, sex, treatment, and coping style by sex by treatment interaction effect on stress behaviors. Specifically, compared to controls, caffeine reduced stress behavior in only reactive males. We also observed significant differential baseline gene expression within the adenosine signaling pathway between the reactive and proactive strains, where reactive zebrafish expressed higher levels of adenosine receptors A1B, A2Ab, A2B, and adenosine deaminase and lower levels of adenosine receptor A2Aa than proactive zebrafish. These findings indicate that variation in adenosine signaling between the stress coping styles and sexes may be contributing to differences in anxiety-related behavior.

animal behavior and cognition↗

bioRxiv2025

Stress Coping Style Alters Functional Brain Network Activity to Acute Stressor

Consistent individual differences in behavior (e.g., personality types, stress coping styles) are a common occurrence across animal taxa. One hypothesis poses that the resulting constraints for within-individual behavioral variation may also lead to constraints for the evolution of behavior. With stress coping styles seen across taxa, it suggests a common underlying proximate mechanism. In this study we investigated neural activity patterns across the brain by quantifying immediate early gene expression in individuals with alternative stress coping styles in response to an acute stressor in zebrafish (Danio rerio). While immediate early gene expression levels of individual brain regions in the aversive brain network were similar across groups, functional network activity differed. There were several differences across groups including interactions between the basolateral amygdala and hippocampal homologs. One brain area that had many different connections across groups was the central gray. There were many differences involving central gray activity between proactive and reactive fish at baseline suggesting that baseline activity may prime for the reaction to stress. Collectively, baseline brain activity can predict behaviors, suggesting that these differences in brain interactions at baseline may be important for biasing behavioral responses to stressors that characterizes a stress coping style. Significance StatementIt is well known that individuals cope with stress in different ways but the underlying mechanisms are not well understood. In this study we investigate how different brain regions interact under stress in animals of different stress coping styles. We investigated activity patterns across several brain regions in fish with a passive or active response to stress. We used an innovative statistical method that allowed us to compare how the brain regions function together under stress. The central gray was the most different between proactive and reactive groups, suggesting that this region is important for biasing the response to stressors. Further baseline functional connectivity differed the most between groups, suggesting that activity at baseline is important for biasing the response to stress mainly through connections with the central gray. Ultimately, functional neural network activity better explains stress behaviors than individual brain activity.

neuroscience↗

bioRxiv2025

Territory proximity influences aggression and modulates the relationship between social dominance and oxidative stress in a highly social African cichlid fish

High social rank has many benefits, including priority access to mates and resources. However, maintaining high rank or social dominance can be physiologically costly, particularly in species that engage in agonistic competition to maintain their dominance status. Previous studies have rarely manipulated the intensity of agonistic competition in controlled settings to isolate the cost of social dominance. We utilized males of the cichlid fish Astatotilapia burtoni to investigate how the degree of territoriality influences patterns of oxidative stress. In this species, high-rank males compete for territories to attract mates. We housed males individually with a defendable structure and used clear tank dividers to allow visual access to a size-matched male neighbor housed in an identical setup to manipulate territoriality. Defendable structures were placed either close to the divider (proximal treatment) or further away (distal treatment). We found that males in the distal treatment expressed higher levels of territorial aggression than those in the proximal treatment. While males in the distal treatment did not display higher levels of oxidative stress, territory proximity influenced the relationships between physiological markers of dominance (i.e., testosterone, gonad size) and oxidative balance. Although our work is not consistent with higher competition increasing the physiological cost of high rank, it suggests that the level of competition influences the regulation of oxidative balance relative to social dominance characteristics. We suggest that manipulating the degree of territoriality in a controlled setting provides a unique opportunity to further our understanding of how individuals manage the trade-offs associated with high rank. Summary StatementManipulating the amount of space between territories results in variability in the degree of territorial aggression and the interaction of physiological markers of social dominance and oxidative stress.

animal behavior and cognition↗

bioRxiv2024

Zebrafish (Danio rerio) behavioral phenotypes not underscored by different gut microbiota

Different animal behavioral phenotypes maintained and selectively bred over multiple generations may be underscored by dissimilar gut microbial community compositions or not have any significant dissimilarity in community composition. Operating within the microbiota-gut-brain axis framework, we anticipated differences in gut microbiome profiles between zebrafish (Danio rerio) selectively bred to display the bold and shy personality types. This would highlight gut microbe-mediated effects on host behavior. To this end, we amplified and sequenced a fragment of the 16S rRNA gene from the guts of bold and shy zebrafish individuals (n=10) via Miseq. We uncovered no significant difference in within-group microbial diversity nor between-group microbial community composition of the two behavioral phenotypes. Interestingly, though not statistically different, we determined that the gut microbial community of the bold phenotype was dominated by Burkholderiaceae, Micropepsaceae, and Propionibacteriaceae. In contrast, the shy phenotype was dominated by Beijerinckaceae, Pirelullacaeae, Rhizobiales_Incertis_Sedis, and Rubinishaeraceae. The absence of any significant difference in gut microbiota profiles between the two phenotypes would suggest that in this species, there might exist a stable "core" gut microbiome, regardless of behavioral phenotypes, and or possibly, a limited role for the gut microbiota in modulating this selected-for host behavior. This is the first study to characterize the gut microbial community of distinct innate behavioral phenotypes of the zebrafish (that are not considered dysbiotic states) and not rely on antibiotic or probiotic treatments to induce changes in behavior. Such studies are crucial to our understanding of the modulating impacts of the gut microbiome on normative animal behavior.

animal behavior and cognition↗

bioRxiv2024

Bold zebrafish (danio rerio) learn faster in an associative learning task

Animals differ in their ability to learn. One potential factor contributing to learning differences is personality types. We investigated the relationship between learning and the bold-shy continuum by comparing performance of bold and shy zebrafish in conditioned place preference (CPP) and 2 choice tasks. Bold fish learned significantly faster than the shy fish but there were no differences in their final performance. When tested in the 2 choice task, we found no clear evidence of learning, however bold fish made more initial choices than shy fish. Overall,our study suggests that bold fish tend to be faster learners when compared to shy fish. The lack of differences in the final change in behavior suggests that the learning difference is due to neophobic tendencies and resulting initial interactions with the learning stimulus.

animal behavior and cognition↗

bioRxiv2020

Npas4a expression in the teleost forebrain is associated with stress coping style differences in fear learning

Learning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. An animals stress coping style (e.g. proactive-reactive axis) is known to influence how it encodes salient events. However, the neural and molecular mechanisms underlying these stress coping style differences in learning are unknown. Further, while a number of neuroplasticity-related genes have been associated with alternative stress coping styles, it is unclear if these genes may bias the development of conditioned behavioral responses to stressful stimuli, and if so, which brain regions are involved. Here, we trained adult zebrafish to associate a naturally aversive olfactory cue with a given context. Next, we investigated if expression of two neural plasticity and neurotransmission-related genes (npas4a and gabbr1a) were associated with the contextual fear conditioning differences between proactive and reactive stress coping styles. Reactive zebrafish developed a stronger conditioned fear response and showed significantly higher npas4a expression in the medial and lateral zones of the dorsal telencephalon (Dm, Dl), and the supracommissural nucleus of the ventral telencephalon (Vs). Our findings suggest that the magnitude of expression of activity-dependent genes like npas4a may be differentially expressed across several interconnected forebrain regions in response to fearful stimuli and promote biases in fear learning among different stress coping styles.

animal behavior and cognition↗

bioRxiv2019

Differential effects of ethanol on behavior and GABAA receptor subunit expression in zebrafish (Danio rerio) with alternative stress coping styles

Variation in stress responses between individuals is linked to factors ranging from stress coping styles to sensitivity of neurotransmitter systems. Many anxiolytic compounds (e.g. ethanol) can increase stressor engagement through modulation of neurotransmitter systems and are used to investigate stress response mechanisms. Here we assessed the role of the GABAA system on the variation of the behavioral stress response by comparing individuals differing in stress coping styles that were chronically treated with ethanol. Specifically, we investigated resulting changes in stress-related behavior and whole-brain GABAA receptor subunits (gabra1, gabra2, gabrd, & gabrg2) in response to a novelty stressor. There were significant main and interaction effects on two stress-related behaviors, where the ethanol-treated proactive individuals showed lower stress-related behaviors than their reactive counterparts. Proactive individuals showed significantly higher expression of gabra1, gabra2, and gabrg2 compared to reactive individuals and ethanol treatment resulted in upregulation of gabra1 and gabrg2 in both stress coping styles. These results show that differences in stress-related behaviors between stress coping styles may be facilitated in part by expression of select GABAA receptor subunits.

neuroscience↗

bioRxiv2019

Contextual fear learning and memory differ between stress coping styles in zebrafish

Animals frequently overcome stressors and the ability to learn and recall these salient experiences is essential to an individuals survival. As part of an animals stress coping style, behavioral and physiological responses to stressors are often consistent across contexts and time. However, we are only beginning to understand how cognitive traits can be biased by different coping styles. Here we investigate learning and memory differences in zebrafish (Danio rerio) displaying proactive and reactive stress coping styles. We assessed learning rate and memory duration using an associative fear conditioning paradigm that trained zebrafish to associate a context with exposure to a natural olfactory alarm cue. Our results show that both proactive and reactive zebrafish learn and remember this fearful association. However, we note significant interaction effects between stress coping style and cognition. Zebrafish with the reactive stress coping style acquired the fear memory at a significantly faster rate than proactive fish. While both stress coping styles showed equal memory recall one day post-training, reactive zebrafish showed significantly stronger recall of the conditioned context relative to proactive fish four days post-training. Through understanding how stress coping strategies promote biases in processing salient information, we gain insight into mechanisms that can constrain adaptive behavioral responses.

animal behavior and cognition↗

bioRxiv2019

Microhabitat predicts species differences in exploratory behavior in Lake Malawi cichlids

Encountering and adaptively responding to unfamiliar or novel stimuli is a fundamental challenge facing animals and is linked to fitness. Behavioral responses to novel stimuli, or exploratory behavior, can differ strongly between closely related species; however, the ecological and evolutionary factors underlying these differences are not well understood, in part because most comparative investigations have focused on only two species. In this study, we investigate exploratory behavior across 23 species in a previously untested vertebrate system, Lake Malawi cichlid fishes, which comprises hundreds of phenotypically diverse species that have diverged in the past one million years. We investigate behavioral variation across species, across microhabitats, and across environmental contexts. We find strong species differences in behavior that are associated with microhabitat, demonstrate that intermediate microhabitats are associated with higher levels of exploratory behavior, show that patterns of behavioral covariation across contexts are characteristic of modular complex traits, and contrast Malawi cichlid data with behavioral data from selectively bred high-and low-exploratory zebrafish. Taken together, our results tie ecology to species differences in behavior, and highlight Lake Malawi cichlids as a powerful system for understanding the evolution, ecology, and biology of natural behavioral variation. HighlightsO_LIMalawi cichlids exhibit high phenotypic variance in exploratory behaviors C_LIO_LISpecies differences in exploratory behavior are explained by microhabitat C_LIO_LIRock-dwelling species exhibit strong edge preferences across assays C_LIO_LIIntermediate habitats are associated with "high exploratory" open field behavior C_LIO_LIPatterns of behavioral covariance across contexts are modular in Malawi cichlids C_LI

animal behavior and cognition↗