Abstract
Learning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. An animal’s 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 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.
Highlights
Learning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors
Consistent with previous findings, we found that reactive (HSB) zebrafish showed an increased conditioned fear response relative to proactive (LSB) individuals (Fig. 1)[30]
We found that npas4a expression was significantly higher in several key forebrain regions of reactive zebrafish
Summary
Learning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. The risk-averse reactive individuals tend to show faster acquisition of aversive paradigms that require avoidance or reduced levels of activity[17,18,19] Despite these findings, the neuromolecular mechanisms and regional brain activity underlying these stress coping style differences in learning are not well understood. Both of these genes were found to have significantly upregulated whole-brain expression at baseline in selectively-bred reactive zebrafish, which separately showed faster acquisition of a contextual conditioned fear response towards an aversive olfactory alarm cue (alarm substance)[22,30] It is unknown if expression of these genes in specific brain regions are more directly associated with proactive–reactive differences in fear learning. The majority of this circuitry has been characterized in rodent models, with putatively homologous structures identified in the teleost forebrain which have been shown to be critical for contextual fear learning and adaptive responses to s tress[32,33,34,35]
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