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By recording from the Drosophila mushroom body during active odor navigation, Zolin et al. reveal that dopaminergic reinforcement pathways encode rewards and goal-directed actions through similar patterns of neural activity and dopamine release. Dopamine plays a central role in motivating and modifying behavior, serving to invigorate current behavioral performance and guide future actions through learning. Here we examine how this single neuromodulator can contribute to such diverse forms of behavioral modulation. By recording from the dopaminergic reinforcement pathways of the Drosophila mushroom body during active odor navigation, we reveal how their ongoing motor-associated activity relates to goal-directed behavior. We found that dopaminergic neurons correlate with different behavioral variables depending on the specific navigational strategy of an animal, such that the activity of these neurons preferentially reflects the actions most relevant to odor pursuit. Furthermore, we show that these motor correlates are translated to ongoing dopamine release, and acutely perturbing dopaminergic signaling alters the strength of odor tracking. Context-dependent representations of movement and reinforcement cues are thus multiplexed within the mushroom body dopaminergic pathways, enabling them to coordinately influence both ongoing and future behavior.

Olfactory systems must detect and discriminate amongst an enormous variety of odorants(1). To contend with this challenge, diverse species have converged on a common strategy in which odorant identity is encoded through the combinatorial activation of large families of olfactory receptors(1-3), thus allowing a finite number of receptors to detect a vast chemical world. Here we offer structural and mechanistic insight into how an individual olfactory receptor can flexibly recognize diverse odorants. We show that the olfactory receptor MhOR5 from the jumping bristletail(4) Machilis hrabei assembles as a homotetrameric odorant-gated ion channel with broad chemical tuning. Using cryo-electron microscopy, we elucidated the structure of MhOR5 in multiple gating states, alone and in complex with two of its agonists-the odorant eugenol and the insect repellent DEET. Both ligands are recognized through distributed hydrophobic interactions within the same geometrically simple binding pocket located in the transmembrane region of each subunit, suggesting a structural logic for the promiscuous chemical sensitivity of this receptor. Mutation of individual residues lining the binding pocket predictably altered the sensitivity of MhOR5 to eugenol and DEET and broadly reconfigured the receptor's tuning. Together, our data support a model in which diverse odorants share the same structural determinants for binding, shedding light on the molecular recognition mechanisms that ultimately endow the olfactory system with its immense discriminatory capacity.

Long-lasting internal arousal states motivate and pattern ongoing behaviour, enabling the temporary emergence of innate behavioural programs that serve the needs of an animal, such as fighting, feeding, and mating. However, how internal states shape sensory processing or behaviour remains unclear. In Drosophila, male flies perform a lengthy and elaborate courtship ritual that is triggered by the activation of sexually dimorphic P1 neurons(1-5), during which they faithfully follow and sing to a female(6,7). Here, by recording from males as they court a virtual 'female', we gain insight into how the salience of visual cues is transformed by a male's internal arousal state to give rise to persistent courtship pursuit. The gain of LC10a visual projection neurons is selectively increased during courtship, enhancing their sensitivity to moving targets. A concise network model indicates that visual signalling through the LC10a circuit, once amplified by P1-mediated arousal, almost fully specifies a male's tracking of a female. Furthermore, P1 neuron activity correlates with ongoing fluctuations in the intensity of a male's pursuit to continuously tune the gain of the LC10a pathway. Together, these results reveal how a male's internal state can dynamically modulate the propagation of visual signals through a high-fidelity visuomotor circuit to guide his moment-to-moment performance of courtship.

Animals rely on the relative timing of events in their environment to form and update predictive associations, but the molecular and circuit mechanisms for this temporal sensitivity remain incompletely understood. Here, we show that olfactory associations in Drosophila can be written and reversed on a trial-by-trial basis depending on the temporal relationship between an odor cue and dopaminergic reinforcement. Through the synchronous recording of neural activity and behavior, we show that reversals in learned odor attraction correlate with bidirectional neural plasticity in the mushroom body, the associative olfactory center of the fly. Two dopamine receptors, DopR1 and DopR2, contribute to this temporal sensitivity by coupling to distinct second messengers and directing either synaptic depression or potentiation. Our results reveal how dopamine-receptor signaling pathways can detect the order of events to instruct opposing forms of synaptic and behavioral plasticity, allowing animals to flexibly update their associations in a dynamic environment.

What would it take to engineer a brain circuit to perform a new kind of computation or to augment an existing brain computation with additional information? Perhaps you could augment a memory circuit (starting with, say, a mouse) so that it could tap into digital data, boost the capacity of working memory so that dozens of things could be held in mind at once, or enable algorithms from computer science to be run on in-brain wetware.

The olfactory system must recognize and discriminate amongst an enormous variety of chemicals in the environment. To contend with such diversity, insects have evolved a family of odorant-gated ion channels comprised of a highly conserved co-receptor (Orco) and a divergent odorant receptor (OR) that confers chemical specificity. Here, we present the single-particle cryo-electron microscopy structure of an Orco homomer from the parasitic fig wasp Apocrypta bakeri at 3.5 A resolution, providing structural insight into this receptor family. Orco possesses a novel channel architecture, with four subunits symmetrically arranged around a central pore that diverges into four lateral conduits that open to the cytosol. The Orco tetramer has few inter-subunit interactions within the membrane and is bound together by a small cytoplasmic anchor domain. The minimal sequence conservation among ORs maps largely to the pore and anchor domain, shedding light on how the architecture of this receptor family accommodates its remarkable sequence diversity and facilitates the evolution of odour tuning.

Courtship rituals serve to reinforce reproductive barriers between closely related species. Drosophila melanogaster and Drosophila simulans exhibit reproductive isolation, owing in part to the fact that D. melanogaster females produce 7,11-heptacosadiene, a pheromone that promotes courtship in D. melanogaster males but suppresses courtship in D. simulans males. Here we compare pheromone-processing pathways in D. melanogaster and D. simulans males to define how these sister species endow 7,11-heptacosadiene with the opposite behavioural valence to underlie species discrimination. We show that males of both species detect 7,11-heptacosadiene using homologous peripheral sensory neurons, but this signal is differentially propagated to P1 neurons, which control courtship behaviour. A change in the balance of excitation and inhibition onto courtship-promoting neurons transforms an excitatory pheromonal cue in D. melanogaster into an inhibitory cue in D. simulans. Our results reveal how species-specific pheromone responses can emerge from conservation of peripheral detection mechanisms and diversification of central circuitry, and demonstrate how flexible nodes in neural circuits can contribute to behavioural evolution.

Animals adapt their behaviors to specific ecological niches, but the genetic and cellular basis of nervous system evolution is poorly understood. We have compared the olfactory circuits of the specialist Drosophila sechellia-which feeds exclusively on Morinda citrifolia fruit-with its generalist cousins D. melanogaster and D. simulans. We show that D. sechellia exhibits derived odor-evoked attraction and physiological sensitivity to the abundant Morinda volatile hexanoic acid and characterize how the responsible sensory receptor (the variant ionotropic glutamate receptor IR75b) and attraction-mediating circuit have evolved. A single amino acid change in IR75b is sufficient to recode it as a hexanoic acid detector. Expanded representation of this sensory pathway in the brain relies on additional changes in the IR75b promoter and trans-acting loci. By contrast, higher-order circuit adaptations are not apparent, suggesting conserved central processing. Our work links olfactory ecology to structural and regulatory genetic changes influencing nervous system anatomy and function.

A major aim of sociogenomic research is to uncover common principles in the molecular evolution of sociality. This endeavor has been hampered by the small number of specific genes currently known to function in social behavior. Here we provide several lines of evidence suggesting that ants have evolved a large and novel clade of odorant receptor (OR) genes to perceive hydrocarbon-based pheromones, arguably the most important signals in ant communication. This genomic expansion is also mirrored in the ant brain via a corresponding expansion of a specific cluster of glomeruli in the antennal lobe. We show that in the clonal raider ant, hydrocarbon-sensitive basiconic sensilla are found only on the ventral surface of the female antennal club. Correspondingly, nearly all genes in a clade of 180 ORs within the 9-exon subfamily of ORs are expressed exclusively in females and are highly enriched in expression in the ventral half of the antennal club. Furthermore, we found that across species and sexes, the number of 9-exon ORs expressed in antennae is tightly correlated with the number of glomeruli in the antennal lobe region innervated by odorant receptor neurons from basiconic sensilla. Evolutionary analyses show that this clade underwent a striking gene expansion in the ancestors of all ants and slower but continued expansion in extant ant lineages. This evidence suggests that ants have evolved a large clade of genes to support pheromone perception and that gene duplications have played an important role in the molecular evolution of ant communication.

Ingestion is a highly regulated behavior that integrates taste and hunger cues to balance food intake with metabolic needs. To study the dynamics of ingestion in the vinegar fly Drosophila melanogaster, we developed Expresso, an automated feeding assay that measures individual meal-bouts with high temporal resolution at nanoliter scale. Flies showed discrete, temporally precise ingestion that was regulated by hunger state and sucrose concentration. We identify 12 cholinergic local interneurons (IN1, for "ingestion neurons'') necessary for this behavior. Sucrose ingestion caused a rapid and persistent increase in IN1 interneuron activity in fasted flies that decreased proportionally in response to subsequent feeding bouts. Sucrose responses of IN1 interneurons in fed flies were significantly smaller and lacked persistent activity. We propose that IN1 neurons monitor ingestion by connecting sugar-sensitive taste neurons in the pharynx to neural circuits that control the drive to ingest. Similar mechanisms for monitoring and regulating ingestion may exist in vertebrates.