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Behavioral flexibility for appropriate action selection is an advantage when animals are faced with decisions that will determine their survival or death. In order to arrive at the right decision, animals evaluate information from their external environment, internal state, and past experiences. How these different signals are integrated and modulated in the brain, and how context- and state-dependent behavioral decisions are controlled are poorly understood questions. Studying the molecules that help convey and integrate such information in neural circuits is an important way to approach these questions. Many years of work in different model organisms have shown that dopamine is a critical neuromodulator for (reward based) associative learning. However, recent findings in vertebrates and invertebrates have demonstrated the complexity and heterogeneity of dopaminergic neuron populations and their functional implications in many adaptive behaviors important for survival. For example, dopaminergic neurons can integrate external sensory information, internal and behavioral states, and learned experience in the decision making circuitry. Several recent advances in methodologies and the availability of a synaptic level connectome of the whole-brain circuitry of Drosophila melanogaster make the fly an attractive system to study the roles of dopamine in decision making and state-dependent behavior. In particular, a learning and memory center—the mushroom body—is richly innervated by dopaminergic neurons that enable it to integrate multi-modal information according to state and context, and to modulate decision-making and behavior.

SummaryNeuromodulation permits flexibility of synapses, neural circuits and ultimately behavior. One neuromodulator, dopamine, has been studied extensively in its role as reward signal during learning and memory across animal species. Newer evidence suggests that dopaminergic neurons (DANs) can modulate sensory perception acutely, thereby allowing an animal to adapt its behavior and decision-making to its internal and behavioral state. In addition, some data indicate that DANs are heterogeneous and convey different types of information as a population. We have investigated DAN population activity and how it could encode relevant information about sensory stimuli and state by taking advantage of the confined anatomy of DANs innervating the mushroom body (MB) of the fly Drosophila melanogaster. Using in vivo calcium imaging and a custom 3D image registration method, we find that the activity of the population of MB DANs is predictive of the innate valence of an odor as well as the metabolic and mating state of the animal. Furthermore, DAN population activity is strongly correlated with walking or running, consistent with a role of dopamine in conveying behavioral state to the MB. Together our data and analysis suggest that distinct DAN population activities encode innate odor valence, movement and physiological state in a MB-compartment specific manner. We propose that dopamine shapes innate odor perception through combinatorial population coding of sensory valence, physiological and behavioral context.

Summary Animals continuously evaluate sensory information to decide on their next action. Different sensory cues, however, often demand opposing behavioral responses. How does the brain process conflicting sensory information during decision making? Here, we show that flies use neural substrates attributed to odor learning and memory, including the mushroom body (MB), for immediate sensory integration and modulation of innate behavior. Drosophila melanogaster must integrate contradictory sensory information during feeding on fermenting fruit that releases both food odor and the innately aversive odor CO 2 . Here, using this framework, we examine the neural basis for this integration. We have identified a local circuit consisting of specific glutamatergic output and PAM dopaminergic input neurons with overlapping innervation in the MB-β′2 lobe region, which integrates food odor and suppresses innate avoidance. Activation of food odor-responsive dopaminergic neurons reduces innate avoidance mediated by CO 2 -responsive MB output neurons. We hypothesize that the MB, in addition to its long recognized role in learning and memory, serves as the insect's brain center for immediate sensory integration during instantaneous decision making.

The fruit fly, Drosophila melanogaster, innately avoids even low levels of CO2. CO2 is part of the so-called Drosophila stress odor produced by stressed flies, but also a byproduct of fermenting fruit, a main food source, making the strong avoidance behavior somewhat surprising. Therefore, we addressed whether feeding states might influence the fly's behavior and processing of CO2. In a recent report, we showed that this innate behavior is differentially processed and modified according to the feeding state of the fly. Interestingly, we found that hungry flies require the function of the mushroom body, a higher brain center required for olfactory learning and memory, but thought to be dispensable for innate olfactory behaviors. In addition, we anatomically and functionally characterized a novel bilateral projection neuron connecting the CO2 sensory input to the mushroom body. This neuron was essential for processing of CO2 in the starved fly but not in the fed fly. In this Extra View article, we provide evidence for the potential involvement of the neuromodulator dopamine in state-dependent CO2 avoidance behavior. Taken together, our work demonstrates that CO2 avoidance behavior is mediated by alternative neural pathways in a context-dependent manner. Furthermore, it shows that the mushroom body is not only involved in processing of learned olfactory behavior, as previously suggested, but also in context-dependent innate olfaction.

CO2sensation represents an interesting example of nervous system and behavioral evolutionary divergence. The underlying molecular mechanisms, however, are not understood. Loss ofmicroRNA-279inDrosophila melanogasterleads to the formation of a CO2sensory system partly similar to the one of mosquitoes. Here, we show that a novel allele of the pleiotropic transcription factor Prospero resembles themiR-279phenotype. We use a combination of genetics andin vitroandin vivoanalysis to demonstrate that Pros participates in the regulation ofmiR-279expression, and that reexpression ofmiR-279rescues theprosCO2neuron phenotype. We identify common target molecules ofmiR-279and Pros in bioinformatics analysis, and show that overexpression of the transcription factors Nerfin-1 and Escargot (Esg) is sufficient to induce formation of CO2neurons on maxillary palps. Our results suggest that Prospero restricts CO2neuron formation indirectly viamiR-279and directly by repressing the shared target molecules, Nerfin-1 and Esg, during olfactory system development. Given the important role of Pros in differentiation of the nervous system, we anticipate that miR-mediated signal tuning represents a powerful method for olfactory sensory system diversification during evolution.

Summary In pursuit of food, hungry animals mobilize significant energy resources and overcome exhaustion and fear. How need and motivation control the decision to continue or change behavior is not understood. Using a single fly treadmill, we show that hungry flies persistently track a food odor and increase their effort over repeated trials in the absence of reward suggesting that need dominates negative experience. We further show that odor tracking is regulated by two mushroom body output neurons (MBONs) connecting the MB to the lateral horn. These MBONs, together with dopaminergic neurons and Dop1R2 signaling, control behavioral persistence. Conversely, an octopaminergic neuron, VPM4, which directly innervates one of the MBONs, acts as a brake on odor tracking by connecting feeding and olfaction. Together, our data suggest a function for the MB in internal state-dependent expression of behavior that can be suppressed by external inputs conveying a competing behavioral drive., Graphical Abstract, Highlights • Hunger motivates persistent food odor tracking even without reward • Two synaptically connected MBONs, -γ1pedc>αβ and -α2sc, regulate odor tracking • Octopamine neurons connect feeding and counteract MBON and odor tracking • Dopaminergic neurons and Dop1R2 signaling promote persistent tracking, What drives behavioral persistence versus quitting? Sayin et al. propose that circuit modules in the fly’s learning center and dopamine drive gradually increasing food odor tracking, which can be efficiently suppressed by extrinsic, but directly innervating, feeding-related neuromodulatory neurons.

Summary Olfaction in the fruit fly Drosophila melanogaster is increasingly understood, from ligand-receptor-neuron combinations [1–4] to their axonal projection patterns into the antennal lobe [5, 6]. Drosophila thus offers an excellent opportunity to study the evolutionary and ecological dynamics of olfactory systems. We compared the structure and function of the generalist D. melanogaster with that of specialist D. sechellia , which oviposits exclusively on morinda fruit [7]. Our analyses show that whereas the fruit's headspace was dominated by acids, antennae responded most strongly to hexanoates. D. sechellia exhibited an extraordinarily strong response to methyl hexanoate (MeHex). Behaviorally, D. sechellia was much more attracted to these morinda fruit volatiles than was D. melanogaster . The high sensitivity to MeHex was paralleled by a 2.5×–3× overrepresentation of MeHex neurons on the antenna and a concordant 2.9× increase in volume of the corresponding glomerulus as compared to D. melanogaster . In addition, the MeHex neuron exhibited an extreme sensitivity down to femtograms of its ligand. In contrast, no peripherally mediated shift was found paralleling D. sechellia 's increased attraction to acids. These findings are a demonstration of evolution acting at several levels in the olfactory circuitry in mediating a fruit fly's unique preference for fruit toxic to its sibling species [8–10].

For many insects, including mosquitoes, olfaction is the dominant modality regulating their behavioral repertoire. Many neurochemicals modulate olfactory information in the central nervous system, including the primary olfactory center of insects, the antennal lobe. The most diverse and versatile neurochemicals in the insect nervous system are found in the neuropeptides. In the present study, we analyzed neuropeptides in the antennal lobe of the yellow fever mosquito, Aedes aegypti, a major vector of arboviral diseases. Direct tissue profiling of the antennal lobe by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry indicated the presence of 28 mature products from 10 different neuropeptide genes. In addition, immunocytochemical techniques were used to describe the cellular location of the products of up to seven of these genes within the antennal lobe. Allatostatin A, allatotropin, SIFamide, FMRFamide-related peptides, short neuropeptide F, myoinhibitory peptide, and tachykinin-related peptides were found to be expressed in local interneurons and extrinsic neurons of the antennal lobe. Building on these results, we discuss the possible role of neuropeptide signaling in the antennal lobe of Ae. aegypti. J. Comp. Neurol. 522:592-608, 2014. (c) 2013 Wiley Periodicals, Inc.

In female Aedes aegypti L. mosquitoes, a blood meal induces physiological and behavioral changes. Previous studies have shown that olfactory receptor neurons (ORNs) housed in grooved peg sensilla on the antennae of Ae. aegypti down-regulate their sensitivity to lactic acid, a key component driving host-seeking behavior, which correlates with observed changes in the host-seeking behavior of this species. In the present study, we performed electrophysiological recordings from the most abundant antennal sensillum type, sensilla trichodea. Our results indicate that the response spectra of ORNs contained within most trichoid sensilla do not change in response to blood feeding. However, we observe an increase in sensitivity to primarily indole and phenolic compounds in neurons housed within four of the five functional types of short blunt tipped II trichoid sensilla, both at 24 and 72 h post-blood feeding, which was more pronounced at 24 h than 72 h. Furthermore, sensitivity to undecanone, acetic acid and propionic acid was observed to increase 72 h post-blood meal. Considering the timing of these changes, we believe that these neurons may be involved in driving the orientation behavior of female mosquitoes to oviposition sites, which are known to release these compounds.