Bignell, A. E. | Search bioRxiv

bioRxiv2026

cGMP signaling regulates context-dependent sensory valence in C. elegans

An animals response to chemosensory cues depends on the animals prior experience, internal state, or life stage. However, the molecular mechanisms that regulate sensory valence (i.e., whether a chemosensory cue is attractive or repulsive) remain poorly understood. We investigated the mechanisms that specify sensory valence using the responses of the free-living nematode Caenorhabditis elegans to carbon dioxide (CO2). C. elegans exhibits highly flexible responses to CO2: well-fed animals are repelled by CO2, while both starved animals and well-fed animals raised under high CO2 conditions are attracted to CO2. Here, we show that CO2 attraction in animals raised at high CO2 requires a cGMP signaling pathway that involves the cGMP-dependent protein kinase EGL-4. This pathway does not regulate CO2 response in starved animals, indicating that the role of EGL-4 in mediating CO2 attraction depends on satiety state. Cultivation under high CO2 conditions leads to increased cGMP levels in the CO2-detecting BAG neurons, consistent with a specific requirement for EGL-4 in high-CO2-cultivated animals. We also show that EGL-4 regulates CO2 valence by altering neuropeptide expression in BAG. Our results indicate that sensory valence is established in a context-dependent manner at the level of the primary sensory neuron.

neuroscience↗

bioRxiv2026

Odor tracking in flying Drosophila requires visual reafference and compass neurons

Flying Drosophila critically depend on high-contrast visual surroundings to localize odor sources in still air, yet the neural mechanisms of visual integration for active odor tracking are unknown. We demonstrate that E-PG neurons--head direction cells in the central complex--work in concert with self-generated visual motion signals to maintain a stable heading metric during olfactory navigation in flight. Using a magnetic tether system and a digital "visual clamp", we show that removing the visual feedback generated by a flys own turns (reafference) causes the animal to lose its heading within an odor plume. Thus, olfactory and mechanosensory signals alone are insufficient for plume stabilization. E-PG neurons have been shown to store visual changes in heading during flight. Genetically hyperpolarizing E-PG neurons significantly compromised the flies ability to both acquire and maintain heading toward a food odor. Notably, silencing these neurons did not disrupt basic visual reflexes, such as optomotor gaze stabilization or object tracking, indicating a specific role in odor-directed visual navigation rather than basic visual flight control. While odor was found to modulate the frequency and amplitude of turns independently, E-PG neurons are essential for directing the orientation of corrective saccades toward the plume center. These results establish that visual reafference engages the internal visual compass to sustain a spatial working memory of heading changes between saccades, allowing flies to maintain a straight course and navigate effectively toward an invisible odor source in flight. Significance StatementA crucial brain function that remains largely mysterious is building robust working memory by integrating stimuli across sensory modalities. For flying Drosophila, visual feedback is required to localize an odor source. Recently, a group of cells residing in the navigation center of the fly brain (E-PG neurons) have been shown to function like an internal compass, providing a dynamic working memory of heading changes akin to mammalian head-direction cells. Here, we show that self-generated visual motion signals work with E-PG compass neurons so that the direction of exploratory turns can be stored and recalled to maintain the animals heading within an odor plume during flight.

neuroscience↗