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Animals exhibit innate behaviours to a variety of sensory stimuli including olfactory cues. In Drosophila, one higher olfactory centre, the lateral horn (LH), is implicated in innate behaviour. However, our structural and functional understanding of the LH is scant, in large part due to a lack of sparse neurogenetic tools for this region. We generate a collection of split-GAL4 driver lines providing genetic access to 82 LH cell types. We use these to create an anatomical and neurotransmitter map of the LH and link this to EM connectomics data. We find ~30% of LH projections converge with outputs from the mushroom body, site of olfactory learning and memory. Using optogenetic activation, we identify LH cell types that drive changes in valence behavior or specific locomotor programs. In summary, we have generated a resource for manipulating and mapping LH neurons, providing new insights into the circuit basis of innate and learned olfactory behavior.

Animals exhibit innate behaviours in response to a variety of sensory stimuli such as olfactory cues. In Drosophila, a higher olfactory centre called the lateral horn (LH) is implicated in innate behaviour. However, our knowledge of the structure and function of the LH is scant, due to the lack of sparse neurogenetic tools for this brain region. Here we generate a collection of split-GAL4 driver lines providing genetic access to 82 LH cell-types. We identify the neurotransmitter and axo-dendritic polarity for each cell-type. Using these lines were create an anatomical map of the LH. We found that ∼30% of LH projections converge with outputs from the mushroom body, the site of olfactory learning and memory. Finally, using optogenetic activation of small groups of LH neurons. We identify cell-types that drive changes in either valence or specific motor programs, such as turning and locomotion. In summary we have generated a resource for manipulating and mapping LH neurons in both light and electron microscopy and generated insights into the anatomy and function of the LH.

Evolution has shaped nervous systems to produce stereotyped behavioural responses to ethologically relevant stimuli. For example when laying eggs, female Drosophila avoid geosmin, an odorant produced by toxic moulds. Here we identify second, third, and fourth order neurons required for this innate olfactory aversion. Connectomics data place these neurons in a complete synaptic circuit from sensory input to descending output. We find multiple levels of valence-specific convergence, including a novel form of axo-axonic input onto second order neurons conveying another danger signal, the pheromone of parasitoid wasps. However, we also observe extensive divergence: second order geosmin neurons connect with a diverse array of 80 third order cell types. We find a pattern of convergence of aversive odour channels at this level. Crossing one more synaptic layer, we identified descending neurons critical for egg-laying aversion. Our data suggest a transition from a labelled line organisation in the periphery to a highly distributed central brain representation that is then coupled to distinct descending pathways.

SummaryThe same sensory signal can be interpreted differently according to context. A new study in Drosophila uses cell-type-specific tools to identify neural circuits that integrate context during olfactory processing and surprisingly implicates memory-recall neurons.

The sense of smell influences behaviors in animals, yet how odors are represented in the brain remains unclear. The nose contains different types of olfactory sensory neurons (OSNs), each expressing a particular odorant receptor, and OSNs expressing the same receptors converge their axons on a brain region called a glomerulus. InDrosophila, second order neurons (projection neurons) typically innervate a single glomerulus and send stereotyped axonal projections to the lateral horn. One of the greatest challenges to studying olfaction is the lack of methods allowing activation of specific types of olfactory neurons in an ethologically relevant setting. Most odorants activate many olfactory neurons, and many olfactory neurons are activated by a variety of odorants. As such, it is difficult to identify if individual types of olfactory neurons directly influence a behavior. To address this, we developed a genetic method inDrosophilacalled olfactogenetics in which a narrowly tuned odorant receptor, Or56a, is ectopically expressed in different olfactory neuron types. Stimulation with geosmin (the only known Or56a ligand), in anOr56amutant background leads to specific activation of only the target olfactory neuron type. We used this approach to identify which types of olfactory neurons can directly guide oviposition decisions. We identified 5 OSN-types (Or71a, Or47b, Or49a, Or67b, and Or7a) that, when activated alone, suppress oviposition. Projection neurons partnering with these OSNs share a region of innervation in the lateral horn, suggesting that oviposition site-selection might be encoded in this brain region.Significance StatementThe sense of smell begins by activation of olfactory neurons in the nose. These neurons express an olfactory receptor that binds odorants (volatile chemicals). How the sense of smell is encoded in the brain remains unclear. A key challenge is due to the nature of olfactory receptors themselves - most respond to a wide range of odorants - so it is often impossible to activate just a single olfactory neuron type. We describe here a novel approach inDrosophilacalled ‘olfactogenetics’ which allows the specific experimental activation of any desired olfactory neuron. We use olfactogenetics to identify olfactory neurons and brain regions that guide egg-laying site selection. Olfactogenetics could be a valuable method to link olfactory neuron activities with circuits and behaviors.

Androstadienone, a component of male sweat, has been suggested to function as a human pheromone, an airborne chemical signal causing specific responses in conspecifics. In earlier studies androstadienone has been reported to increase attraction, affect subjects' mood, cortisol levels and activate brain areas linked to social cognition, among other effects. However, the existing psychological evidence is still relatively scarce, especially regarding androstadienone's effects on male behaviour. The purpose of this study was to look for possible behavioural effects in male subjects by combining two previously distinct branches of research: human pheromone research and behavioural game theory of experimental economics. Forty male subjects participated in a mixed-model, double-blind, placebo-controlled experiment. The participants were exposed to either androstadienone or a control stimulus, and participated in ultimatum and dictator games, decision making tasks commonly used to measure cooperation and generosity quantitatively. Furthermore, we measured participants' salivary cortisol and testosterone levels during the experiment. Salivary testosterone levels were found to positively correlate with cooperative behaviour. After controlling for the effects of participants' baseline testosterone levels, androstadienone was found to increase cooperative behaviour in the decision making tasks. To our knowledge, this is the first study to show that androstadienone directly affects behaviour in human males.

Understanding how sensory stimuli are processed in the brain to instruct appropriate behavior is a fundamental question in neuroscience. Drosophila has become a powerful model system to address this problem. Recent advances in characterizing the circuits underlying pheromone processing have put the field in a position to follow the transformation of these chemical signals all the way from the sensory periphery to decision making and motor output. Here we describe the latest advances, outline emerging principles of pheromone processing and discuss future questions.