Behavioural and neurogenetic evidence for emotion primitives in the fruit fly Drosophila: insights from the Open Field Test
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eLife Assessment
This useful study reports findings that support the use of the Open Field Test in Drosophila as a model to study "emotion-like states", which are behavioral responses to several stressful or aversive treatments, and resilience upon their subsequent removal. Behavioral data, by employing established stress-causing treatments and genetic manipulations, are solid. While the results and conceptual framework of this work will be of interest to behaviorists regardless of animal models, the novelty of this work over previous studies could have been clearer.
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Abstract
Emotions, defined as transient states preparing organisms for adaptive responses, are thought to be based on evolutionarily conserved building blocks (“emotion primitives”) that are present across mammalian and other vertebrate species. Whether and to which extent these building blocks are found in insects is largely undefined. In this study, we employ the open field test in fruit flies and focus on wall-following and total walking activity as behavioural indicators of emotion-like states.
Wildtype and transgenic flies were subjected to various conditions, including social isolation, starvation, and exposure to anxiolytic substances prior to behavioural testing in the open field test. The results indicate that wall-following and total walking activity are modulated by these conditions, with generally increased wall-following observed under aversive stimuli and decreased values under positive conditions. Notably, the behaviour was consistent across different times of the day and independent of circadian rhythms. Genetic manipulation of neuromodulatory systems, such as serotonin, dopamine, and neuropeptide F, supports the role of these pathways in modulating emotion-like states in the fruit fly. Activation of reward-related neurons decreased wall-following, while inhibition increased it, aligning with known effects in mammalian models. Additionally, pharmacological treatments with ethanol and diazepam produced predictable changes in wall-following and total walking activity, reinforcing the validity of the open field test as a measure of emotion-like states in the fly.
The findings suggest that Drosophila exhibits core emotion-like states, with wall-following and total walking activity serving as reliable indicators of emotional valence and arousal. Our results promote the use of Drosophila as a powerful genetic model to dissect the neuronal and neurochemical substrates of emotion primitives, shedding light on the evolution of basic emotional processing mechanisms.
Article activity feed
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eLife Assessment
This useful study reports findings that support the use of the Open Field Test in Drosophila as a model to study "emotion-like states", which are behavioral responses to several stressful or aversive treatments, and resilience upon their subsequent removal. Behavioral data, by employing established stress-causing treatments and genetic manipulations, are solid. While the results and conceptual framework of this work will be of interest to behaviorists regardless of animal models, the novelty of this work over previous studies could have been clearer.
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Reviewer #1 (Public review):
Summary:
Animal behavior is continuously influenced by the internal state moment-by-moment, including emotion primitives, as the authors pointed out. Although emotion is a more human-related state, evolutionary conservation is undeniable, which can be inferred by the behavioral manifestation. To further elaborate on the neuronal mechanisms of emotion primitives, the simplest behavioral parameter related to emotional primitives should be well-characterized. In this study, the authors described in detail wall-following behavior (WAFO) and the total walking distance (TOWA) using flies after subjecting them to various conditions or flies being genetically manipulated according to the previous reports that could affect emotion primitives. Overall, the study is well designed and structured. In addition, the …
Reviewer #1 (Public review):
Summary:
Animal behavior is continuously influenced by the internal state moment-by-moment, including emotion primitives, as the authors pointed out. Although emotion is a more human-related state, evolutionary conservation is undeniable, which can be inferred by the behavioral manifestation. To further elaborate on the neuronal mechanisms of emotion primitives, the simplest behavioral parameter related to emotional primitives should be well-characterized. In this study, the authors described in detail wall-following behavior (WAFO) and the total walking distance (TOWA) using flies after subjecting them to various conditions or flies being genetically manipulated according to the previous reports that could affect emotion primitives. Overall, the study is well designed and structured. In addition, the discussion on emotion primitives will be of value to the field.
Strengths:
The strength of this study is its use of a simple behavioral parameter, TOWA, and also a simple design of behavior, WAFO. The importance of the behavioral assay is reproducibility and comparability. In fact, the author demonstrated a summary of comparisons where different treatments result in scalable behavioral changes in WAFO and TOWA.
Weaknesses:
The weakness of the study is the lack of further experiments to support their assumption related to TOWA.
The authors suggested that TOWA can be interpreted as a behavioral proxy for exogenously induced arousal. However, it could be interpreted as higher activity, although the authors argued that the circadian clock increasing locomotor activity around ZT0 and ZT12 does not affect TOWA, and therefore TOWA is not related to the locomotor activity per se. As the author cited, flies lose locomotor activity in the circular arena of 6.6 cm in diameter, whereas they continuously move during a 1-h recording in the authors' arena of 1 cm in diameter.
I would agree that the arena of 1 cm in diameter, but not 6.6 cm in diameter, serves as an exogenous stimulus inducing arousal, and TOWA is manifested by arousal. However, TOWA would also be affected by other behavioral parameters, including the activity, motivation for exploration, or perception of the space. Therefore, it could be reasonable to re-examine some of the flies tested in this study in the circular arena of 6.6 cm in diameter. If arousal is biased by the components presented in Figure 6 and TOWA can assess mainly exogenously induced arousal, the treatment altering TOWA in the arena of 1 cm in diameter would not affect their behavior in the arena of 6.6 cm in diameter. My concern is that Figure 6 may demonstrate too simplistic a diagram to interpret the results. I would suggest adding the experiments using the arena of 6.6 cm diameter or softening the argument.
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Reviewer #2 (Public review):
Summary:
This work seeks to establish the Open Field Test (OFT) as a paradigm to measure emotion-like states in the fruit fly Drosophila. To do this, the authors first applied various stressors and aversive stimuli to wild-type flies and tracked their locomotion. By measuring wall-following (WAFO) and total walking (TOWA), they showed that these behaviors are generally increased by stressors, but return to baseline levels after their removal. Then, they used the same approach to analyze the effects of pharmacological, genetic, and neuronal activity manipulations, showing that diazepam, serotonin, dopamine, and neuropeptide F affect locomotion in the OFT in largely expected ways that are consistent with their functions in rodents. Finally, the authors demonstrate that wild-type fly strains from the laboratory …
Reviewer #2 (Public review):
Summary:
This work seeks to establish the Open Field Test (OFT) as a paradigm to measure emotion-like states in the fruit fly Drosophila. To do this, the authors first applied various stressors and aversive stimuli to wild-type flies and tracked their locomotion. By measuring wall-following (WAFO) and total walking (TOWA), they showed that these behaviors are generally increased by stressors, but return to baseline levels after their removal. Then, they used the same approach to analyze the effects of pharmacological, genetic, and neuronal activity manipulations, showing that diazepam, serotonin, dopamine, and neuropeptide F affect locomotion in the OFT in largely expected ways that are consistent with their functions in rodents. Finally, the authors demonstrate that wild-type fly strains from the laboratory or caught in the wild differ significantly in their OFT behavior, with wild-caught flies generally behaving as if more 'stressed'. Given the numerous advantages of Drosophila, this study can form the foundation for using the OFT in conjunction with this animal model to elucidate the molecular and neuronal mechanisms that underlie emotion primitives.
Strengths:
The main strength of the paper is the rigorous use of several stressful or aversive treatments and their subsequent removal to show that WAFO is a robust proxy for stress-like emotional primitives across multiple stimuli. The pharmacological, molecular, and neuronal activity manipulations, although more limited in scope, lend further credence to the authors' central claim.
Weaknesses:
The conceptual advance of this research is unclear, as previous work (Mohammad et al., 2016, Curr Biol.) carried out similar treatments and manipulations and reached largely similar conclusions. Moreover, while WAFO is a good proxy for 'stress', I am not convinced that TOWA necessarily represents an emotional state in all cases. Indeed, as the authors themselves acknowledge, changes in total walking may be associated with other factors, such as starvation-induced hyperactivity, physical exhaustion after sleep deprivation, increased sex drive after mating, alcohol sedation, etc. Another unclear point is the interpretation of some unexpected results, such as the finding that both serotonin transporter overexpression and its knockdown give the same phenotype. Finally, there are some issues with the use of the OFT in rodent research (e.g., inconsistent effects of anxiolytic drugs; see Rosso et al., 2022, Neurosci Biobehav Rev., for a meta-analysis). These should be explained to place the Drosophila findings in their appropriate context.
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