Biology subjects

Wolf, F. W.

Publications and source records attributed to Wolf, F. W..

6 recordsLinked to original sources

bioRxiv2026

A male-specific neural circuit for appetitive thirst in Drosophila

Thirst is the brain representation of the need to restore water balance. While environmental and interoceptive sensory neurons that assess water availability and status are known, the central brain representation of thirst that determines behavior in Drosophila is less well understood. We identified a male-specific appetitive thirst circuit in Drosophila using circuit mapping, connectomics, and behavior measurements. Male-specific NPF-M neurons receive thirsty seeking information via Allatostatin A (AstA) neuropeptide released from the Janu-AstA projection neuron. In turn, NPF-M neurons release the neuropeptides sNPF, NPF, and DH31 to promote thirsty water seeking and the neurotransmitter acetylcholine to inhibit it. NPF-M neurons regulate multiple motivated behaviors, including appetitive and consummatory thirst, food foraging, and courtship, driven by distinct input neurons. NPF-M neurons output to appetitive and aversive dopaminergic, mushroom body ongoing behavior integration center, and navigation circuits. This circuit exhibits similarities to those for hungry food foraging and courtship. NPF-M and Janu-AstA form a network with OviIN hub neurons that are sex-independent thirst neurons. We suggest that NPF-M neurons form a circuit branch that funnels male-specific information to tune motivated behavior.

neuroscience↗

bioRxiv2025

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

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. 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 StatementUnderstanding 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. Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/662850v1_ufig1.gif" ALT="Figure 1"> View larger version (70K): org.highwire.dtl.DTLVardef@685da2org.highwire.dtl.DTLVardef@1db60f2org.highwire.dtl.DTLVardef@1b9d1a5org.highwire.dtl.DTLVardef@72bd09_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Alcohol tolerance encoding in sleep regulatory circadian neurons in Drosophila

Alcohol tolerance is a simple form of behavioral and neural plasticity that occurs with the first drink. Neural plasticity in tolerance is likely a substrate for longer term adaptations that can lead to alcohol use disorder. Drosophila develop tolerance with characteristics similar to vertebrates, and it is useful model for determining the molecular and circuit encoding mechanisms in detail. Rapid tolerance, measured after the first alcohol exposure is completely metabolized, is localized to specific brain regions that are not interconnected in an obvious way. We used a forward neuroanatomical screen to identify three new neural sites for rapid tolerance encoding. One of these was comprised of two groups of neurons, the DN1a and DN1p glutamatergic neurons, that are part of the Drosophila circadian clock. We localized rapid tolerance to the two DN1a neurons that regulate arousal by light at night, temperature-dependent sleep timing, and night-time sleep. Two clock neurons that regulate evening activity, LNd6 and the 5th LNv, are postsynaptic to the DN1as and they promote rapid tolerance via the metabotropic glutamate receptor. Thus, rapid tolerance to alcohol overlaps with sleep regulatory neural circuitry, suggesting a mechanistic link.

neuroscience↗

bioRxiv2019

A Canal-Associated Neuron cAMP signalling pathway that regulates C. elegans larval development

Caenorhabditis elegans larval development requires the function of the two Canal-Associated Neurons (CANs): killing the CANs by laser microsurgery or disrupting their development by mutating the gene ceh-10 results in early larval arrest. How these cells promote larval development, however, remains a mystery. In screens for mutations that bypass CAN function, we identified the gene kin-29, which encodes a member of the Salt-Inducible Kinase (SIK) family and a component of a conserved pathway that regulates various C. elegans phenotypes. Like kin-29 loss, gain-of-function mutations in genes that may act upstream of kin-29 or growth in cyclic-AMP analogs bypassed ceh-10 larval arrest, suggesting that a conserved adenylyl cyclase/PKA pathway inhibits KIN-29 to promote larval development and that loss of CAN function results in dysregulation of KIN-29 and larval arrest. The adenylyl cyclase ACY-2 mediates CAN-dependent larval development: acy-2 mutant larvae arrested development with a similar phenotype to ceh-10 mutants, and the arrest phenotype was suppressed by mutations in kin-29. ACY-2 is predominantly expressed in the CANs, and we provide evidence that the acy-2 functions in the CANs to promote larval development. By contrast, cell-specific expression experiments suggest that kin-29 acts in both the hypodermis and neurons, but not in the CANs. Based on our findings, we propose that cAMP produced by ACY-2 in the CANs acts in neighboring neurons and hypodermal cells where it activates PKA and inhibits KIN-29 to promote larval development. We discuss how this conserved pathway could be partitioned between two cells.

developmental biology↗

bioRxiv2017

Satiation State-dependent Dopaminergic Control of Food Seeking in Drosophila

Hunger evokes stereotypic behaviors that favor the discovery of nutrients. The neural pathways that coordinate internal and external cues to motivate food seeking behaviors are only partly known. Drosophila that are food deprived increase locomotor activity, are more efficient in locating a discrete source of nutrition, and are willing to overcome adversity to obtain food. Here we developed a semi-naturalistic assay and show that two distinct dopaminergic neural circuits regulate food-seeking behaviors. One group, the PAM neurons, functions in food deprived flies while the other functions in well fed flies, and both promote food seeking. These satiation state-dependent circuits converge on dopamine D1 receptor-expressing Kenyon cells of the mushroom body, where neural activity promotes food seeking behavior independent of satiation state. These findings provide evidence for active food seeking in well-fed flies that is separable from hunger-driven seeking.

neuroscience↗

bioRxiv2017

Mef2 induction of the immediate early gene Hr38/Nr4a is terminated by Sirt1 to promote ethanol tolerance

Drug naive animals given a single dose of ethanol show changed responses to subsequent doses, including the development of ethanol tolerance and ethanol preference. These simple forms of behavioral plasticity are due in part to changes in gene expression and neuronal properties. Surprisingly little is known about how ethanol initiates changes in gene expression or what the changes do. Here we demonstrate a role in ethanol plasticity for Hr38, the sole Drosophila homolog of the mammalian Nr4a1/2/3 class of immediate early response transcription factors. Acute ethanol exposure induces transient expression of Hr38 and other immediate early neuronal activity genes. Ethanol activates the Mef2 transcriptional activator to induce Hr38, and the Sirt1 histone/protein deacetylase terminates Hr38 induction. Loss of Hr38 decreases ethanol tolerance and causes precocious but short-lasting ethanol preference. Similarly, reduced Mef2 activity in all neurons or specifically in the mushroom body /{beta} neurons decreases ethanol tolerance; Sirt1 promotes ethanol tolerance in these same neurons. Genetically decreasing Hr38 expression levels in Sirt1 null mutants restores ethanol tolerance, demonstrating that both induction and termination of Hr38 expression are important for behavioral plasticity to proceed. These data demonstrate that Hr38 functions as an immediate early transcription factor that promotes ethanol behavioral plasticity.

neuroscience↗