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. 2025 Oct 8:ENEURO.0259-25.2025.
doi: 10.1523/ENEURO.0259-25.2025. Online ahead of print.

A single NPFR neuropeptide F receptor neuron that regulates thirst behaviors in Drosophila

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Free article

A single NPFR neuropeptide F receptor neuron that regulates thirst behaviors in Drosophila

Donnoban Orozco Ramirez et al. eNeuro. .
Free article

Abstract

Thirst is a strongly motivated internal state that is represented in central brain circuits that are only partially understood. Water seeking is a discrete step of the thirst behavioral sequence that is amenable to uncovering the mechanisms for motivational properties such as goal-oriented behavior, value encoding, and behavioral competition. In Drosophila water seeking is regulated by the NPY-like neuropeptide NPF, however the circuitry for NPF-dependent water seeking is unknown. To uncover the downstream circuitry, we identified the NPF receptor NPFR and the neurons it is expressed in as being acutely critical for thirsty water seeking in males. Refinement of the NPFR pattern uncovered a role for a single neuron, the L1-l, in promoting thirsty water seeking. The L1-l neuron increases its activity in thirsty flies and is involved in the regulation of dopaminergic neurons in long-term memory formation. Thus, NPFR and its ligand NPF, already known for its role in feeding behavior, are also important for a second ingestive behavior.Significance Statement Understanding how a single motivated behavior is represented in the neural circuitry of the brain will help uncover drive-specific and universal encoding mechanisms for motivation. Thirst is useful because it is relatively simple compared to feeding behavior and it is strongly motivated. The fly Drosophila, with its straightforward genetics and complete connectome, is helpful in determining a complete circuit for thirsty water seeking. Here we discover a single neuron in the fly brain, the L1-l, that actively receives input from the NPY-like neuropeptide NPF to promote water seeking. Prior findings suggest that the L1-l modulates valence inputs into sensory processing centers, suggesting a similar function in thirsty seeking.

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