Dopaminergic Neurons Linking Threat Processing to Cardiac Modulation and Locomotor Responses

Q: What are the key findings of this study?

Mechanical threat and optogenetic activation of DA-WED dopaminergic neurons induced a ~10% cardiac deceleration (p<0.001) and promoted defensive locomotion in Drosophila.

Q: What is the clinical evidence from this study?

Population: Threat-induced cardiac deceleration and locomotor responses in Drosophila melanogaster. Intervention: Mechanical threat (air puff) and optogenetic/genetic manipulation of DA-WED dopaminergic neurons and cardiomyocytes vs. Driver-less or retinal-unfed controls. Primary outcome: Percentage change in heart rate (HR) from baseline (p=<0.001).

Q: What does this research mean for the field?

In Drosophila, mechanical threat activates DA-WED dopaminergic neurons to induce cardiac deceleration, which contributes to driving defensive locomotor responses. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To identify the neural circuits that connect mechanical threat detection to heart rate changes and determine whether altered cardiac dynamics influence defensive locomotion in Drosophila.

Masato Tsuji; Daisuke Jinkoma; Yuki Uemura; Ayako Ogasawara; Kazuo Emoto

doi:10.7554/elife.111256.2

October 27, 2026eLifeOpen Access

Dopaminergic Neurons Linking Threat Processing to Cardiac Modulation and Locomotor Responses

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Key result

Optogenetic activation of dopaminergic neurons slows heart rate by ~10% alongside defensive behavior.

P<0.001

Why the study?

The neuronal mechanisms linking threat processing to cardiac modulation during defensive states, as well as the potential contribution of cardiac dynamics to behavioral output, remain poorly understood.

Does dopaminergic signaling through DA-WED neurons mediate mechanical threat-induced cardiac deceleration and coordinate locomotor defensive responses in Drosophila melanogaster?

Key Points

To identify the neural circuits that connect mechanical threat detection to heart rate changes and determine whether altered cardiac dynamics influence defensive locomotion in Drosophila.
Monitored heart rate in the conical cardiac chamber alongside locomotor tracking in tethered Drosophila exposed to frontally applied 0.5 s air puffs at varying flow rates (20, 50, and 200 mL/min).
Characterized, silenced, and optogenetically activated two pairs of dopaminergic DA-WED neurons, accompanied by calcium imaging during mechanical threat delivery.
Optogenetically stimulated cardiomyocytes directly to quantitatively match threat-evoked cardiac slowing and observed the resulting effects on walking behavior.
Mechanical air puffs triggered a transient cardiac deceleration of roughly 10% peaking around 0.2 to 0.5 s post-stimulus, followed by a persistent rise in walking fraction peaking around 1 to 1.5 s.
DA-WED dopaminergic neurons were activated by mechanical threat; silencing them attenuated puff-induced cardiac deceleration, whereas optogenetic activation of DA-WED neurons alone induced cardiac deceleration.
Direct optogenetic deceleration of cardiomyocytes in the absence of external threat led to increased locomotion.

Structured PICO

Does dopaminergic signaling through DA-WED neurons mediate mechanical threat-induced cardiac deceleration and coordinate locomotor defensive responses in Drosophila melanogaster?

P

Population

Preclinical animal study in fruit flies (Drosophila melanogaster) examining dopaminergic regulation of cardiac deceleration and locomotion under mechanical threat.

I

Intervention

Mechanical threat via frontal air puffs (20, 50, or 200 mL/min for 0.5 s, 1 s, 10 s, or 20 s), neuronal silencing (via TNT or Kir2.1 expression), thermogenetic activation (via dTrpA1 shifting temperature from 21°C to 28°C for 5 min), and optogenetic activation (via CsChrimson with 1 s red light and all-trans retinal feeding) of monoaminergic/DA-WED neurons and cardiomyocytes.

C

Comparator

Baseline pre-stimulation periods (10 s or 60 s prior to air puff/light/heat), driver-less or empty-driver genetic controls, wild-type controls, and optogenetic controls without all-trans retinal (Ret-) feeding.

O

Outcome

Percentage change in heart rate (HR, cardiac deceleration) from the 10 s baseline period during or immediately following (1 s or 10 s) mechanical threat or neuronal manipulation, quantified via infrared video optical flow or confocal microscopy of GFP-labeled cardiomyocytes in the conical chamber.surrogate

Main Result

p-value: p=<0.001

This basic neuroscience study in Drosophila identifies a specific dopaminergic pathway (DA-WED neurons) that links central threat processing to cardiac deceleration and defensive locomotion, offering preclinical insight into bidirectional brain-heart communication during defensive states.

Limitations

Preclinical study conducted entirely in Drosophila melanogaster
Optogenetically induced cardiac deceleration patterns were not identical to mechanically induced counterparts
Retinal-unfed control flies exhibited a modest locomotor increase following green-light illumination
Does not exclude the possibility that DA-WED neurons influence locomotion partially independent of cardiac deceleration

Implication

Does not inform clinical practice; extends dopaminergic threat-cardiac coupling to Drosophila models.

Abstract

Heartbeat and behavior are tightly coordinated during defensive states, yet the neuronal mechanisms linking threat processing to cardiac modulation—and the potential contribution of cardiac dynamics to behavioral output—remain poorly understood. Here we show in Drosophila that mechanical threat triggers locomotion together with cardiac deceleration. We identify two pairs of dopaminergic neurons, termed DA-WED neurons, that mediate this cardiac response: silencing these neurons markedly attenuates threat-induced cardiac deceleration, whereas optogenetic activation induces cardiac deceleration in the absence of threat. Calcium imaging further shows that DA-WED neurons are activated by mechanical threat. Linking cardiac dynamics to behavior, direct optogenetic manipulation of cardiomyocytes that quantitatively reproduces threat-evoked cardiac deceleration is accompanied by increased locomotion. Together, these results identify a dopaminergic descending pathway that links threat processing to cardiac modulation and suggest that cardiac dynamics may contribute to shaping defensive behavior.

Discussion

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Cite This Study

Tsuji et al. (2026) studied Threat-induced cardiac deceleration and locomotor responses in Drosophila melanogaster. Mechanical threat (air puff) and optogenetic/genetic manipulation of DA-WED dopaminergic neurons and cardiomyocytes vs. Driver-less or retinal-unfed controls was evaluated on Percentage change in heart rate (HR) from baseline (p=<0.001). Mechanical threat and optogenetic activation of DA-WED dopaminergic neurons induced a ~10% cardiac deceleration (p<0.001) and promoted defensive locomotion in Drosophila.

synapsesocial.com/papers/6ae2e1ca61f440a81e656f47 https://doi.org/10.7554/elife.111256.2

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Dopaminergic Neurons Linking Threat Processing to Cardiac Modulation and Locomotor Responses

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Dopaminergic Neurons Linking Threat Processing to Cardiac Modulation and Locomotor Responses

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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