A Programmable Ontology Encompassing the Functional Logic of the Drosophila Brain

The Drosophila brain has only a fraction of the number of neurons of higher organisms such as mice. Yet the sheer complexity of its neural circuits recently revealed by large connectomics datasets suggests that computationally modeling the function of fruit fly brain at this scale posits significant challenges. To address these challenges, we present here a programmable ontology that expands the scope of the current Drosophila brain anatomy ontologies to encompass the functional logic of the fly brain. The programmable ontology provides a language not only for defining functional circuit motifs but also for programmatically exploring their functional logic. To achieve this goal, we tightly integrated the programmable ontology with the workflow of the interactive FlyBrainLab computing platform. As part of the programmable ontology, we developed NeuroNLP++, a web application that supports free-form English queries for constructing functional brain circuits fully anchored on the available connectome/synaptome datasets, and the published worldwide literature. In addition, we present a methodology for including a model of the space of odorants into the programmable ontology, and for modeling olfactory sensory circuits of the antenna of the fruit fly brain that detect odorant sources. Furthermore, we describe a methodology for modeling the functional logic of the antennal lobe circuit consisting of massive local feedback loops, a characteristic feature observed across Drosophila brain regions. Finally, using a circuit library, we demonstrate the power of our methodology for interactively exploring the functional logic of the massive number of feedback loops in the antennal lobe.

The Functional Logic of Odor Information Processing in the Drosophila Antennal Lobe

In the early olfactory pathway of Drosophila, Olfactory Sensory Neurons (OSNs) multiplicatively encode the odorant identity and the concentration profile. Projection Neurons (PNs) responses in the Antennal Lobe (AL), in turn, exhibit strong transients at odorant onset/offset and stable steady-state behavior. What is the functional logic the of diverse set of Local Neurons (LNs) in the AL Addressing this question may shed light on the key characteristics of odor information processing in the AL, and odorant recognition and olfactory associative learning in the downstream neuropils of the early olfactory system. To address the computation performed by each LN type, we exhaustively evaluated all circuit configurations of the Antennal Lobe. We found that, across model parameterizations, presynaptic inhibition of the OSN-to-PN synapse is essential for odorant identity recovery in steady-state, while postsynaptic excitation and inhibition facilitate on-/off-set event detection. The onset and offset events indicate changing odorant identities, and together with the identity recovery in steady-state, suggest that the AL is an event-based odorant identity recovery processor.

Non-synaptic interactions between olfactory receptor neurons, a possible key feature of odor processing in flies

When flies explore their environment, they encounter odors in complex, highly intermittent plumes. To navigate a plume and, for example, find food, they must solve several challenges, including reliably identifying mixtures of odorants and their intensities, and discriminating odorant mixtures emanating from a single source from odorants emitted from separate sources and just mixing in the air. Lateral inhibition in the antennal lobe is commonly understood to help solving these challenges. With a computational model of the Drosophila olfactory system, we analyze the utility of an alternative mechanism for solving them: Non-synaptic (“ephaptic”) interactions (NSIs) between olfactory receptor neurons that are stereotypically co-housed in the same sensilla. We find that NSIs improve mixture ratio detection and plume structure sensing and do so more efficiently than the traditionally considered mechanism of lateral inhibition in the antennal lobe. The best performance is achieved when both mechanisms work in synergy. However, we also found that NSIs decrease the dynamic range of co-housed ORNs, especially when they have similar sensitivity to an odorant. These results shed light, from a functional perspective, on the role of NSIs, which are normally avoided between neurons, for instance by myelination.

Parallel Processing of Olfactory and Mechanosensory Information in the Honey Bee Antennal Lobe

In insects, neuronal responses to clean air have so far been reported only episodically in moths. Here we present results obtained by fast two-photon calcium imaging in the honey bee Apis mellifera, indicating a substantial involvement of the antennal lobe, the first olfactory neuropil, in the processing of mechanical stimuli. Clean air pulses generate a complex pattern of glomerular activation that provides a code for stimulus intensity and dynamics with a similar level of stereotypy as observed for the olfactory code. Overlapping the air pulses with odor stimuli reveals a superposition of mechanosensory and odor response codes with high contrast. On the mechanosensitive signal, modulations were observed in the same frequency regime as the oscillatory motion of the antennae, suggesting a possible way to detect odorless airflow directions. The transduction of mechanosensory information via the insect antennae has so far been attributed primarily to Johnston’s organ in the pedicel of the antenna. The possibility that the antennal lobe activation by clean air originates from Johnston’s organ could be ruled out, as the signal is suppressed by covering the surfaces of the otherwise freely moving and bending antennae, which should leave Johnston’s organ unaffected. The tuning curves of individual glomeruli indicate increased sensitivity at low-frequency mechanical oscillations as produced by the abdominal motion in waggle dance communication, suggesting a further potential function of this mechanosensory code. The discovery that the olfactory system can sense both odors and mechanical stimuli has recently been made also in mammals. The results presented here give hope that studies on insects can make a fundamental contribution to the cross-taxa understanding of this dual function, as only a few thousand neurons are involved in their brains, all of which are accessible by in vivo optical imaging.

Olfactory System Morphology Suggests Colony Size Drives Trait Evolution in Odorous Ants (Formicidae: Dolichoderinae)

In social insects colony fitness is determined in part by individual worker phenotypes. Across ant species, colony size varies greatly and is thought to affect worker trait variation in both proximate and ultimate ways. Little is known about the relationship between colony size and worker trait evolution, but hypotheses addressing the role of social structure in brain evolution suggest workers of small-colony species may have larger brains or larger brain regions necessary for complex behaviors. In previous work on odorous ants (Formicidae: Dolichoderinae) we found no correlation between colony size and these brain properties, but found that relative antennal lobe size scaled negatively with colony size. Therefore, we now test whether sensory systems scale with colony size, with particular attention to olfactory components thought to be involved in nestmate recognition. Across three species of odorous ants, Forelius mccooki, Dorymyrmex insanus, and D. bicolor, which overlap in habitat and foraging ecology but vary in colony size, we compare olfactory sensory structures, comparing those thought to be involved in nestmate recognition. We use the visual system, a sensory modality not as important in social communication in ants, as a control comparison. We find that body size scaling largely explains differences in eye size, antennal length, antennal sensilla density, and total number of olfactory glomeruli across these species. However, sensilla basiconica and olfactory glomeruli in the T6 cluster of the antennal lobe, structures known to be involved in nestmate recognition, do not follow body size scaling observed for other structures. Instead, we find evidence from the closely related Dorymyrmex species that the larger colony species, D. bicolor, invests more in structures implicated in nestmate recognition. To test for functional consequences, we compare nestmate and non-nestmate interactions between these two species and find D. bicolor pairs of either type engage in more interactions than D. insaus pairs. Thus, we do not find evidence supporting a universal pattern of sensory system scaling associated with changes in colony size, but hypothesize that observed differences in the olfactory components in two closely related Dorymyrmex species are evidence of a link between colony size and sensory trait evolution.

Interspecific variation of antennal lobe composition among four hornet species

Olfaction is a crucial sensory modality underlying foraging, social and mating behaviors in many insects. Since the olfactory system is at the interface between the animal and its environment, it receives strong evolutionary pressures that promote neuronal adaptations and phenotypic variations across species. Hornets are large eusocial predatory wasps with a highly developed olfactory system, critical for foraging and intra-specific communication. In their natural range, hornet species display contrasting ecologies and olfactory-based behaviors, which might match to adaptive shifts in their olfactory system. The first olfactory processing center of the insect brain, the antennal lobe, is made of morphological and functional units called glomeruli. Using fluorescent staining, confocal microscopy and 3D reconstructions, we compared antennal lobe structure, glomerular numbers and volumes in four hornet species (Vespa crabro, Vespa velutina, Vespa mandarinia and Vespa orientalis) with marked differences in nesting site preferences and predatory behaviors. Despite a conserved organization of their antennal lobe compartments, glomeruli numbers varied strongly between species, including in a subsystem thought to process intraspecific cuticular signals. Moreover, specific adaptations involving enlarged glomeruli appeared in two species, V. crabro and V. mandarinia, but not in the others. We discuss the possible function of these adaptations based on species-specific behavioral differences.

Geosmin suppresses defensive behaviour and elicits unusual neural responses in honey bees.

Geosmin is an odorant produced by bacteria in moist soil. It has been found to be extraordinarily relevant to some insects, but the reasons for this are not yet fully understood. Here we report the first tests of the effect of geosmin on honey bees. A stinging assay showed that the defensive behaviour elicited by the bee's alarm pheromone is strongly suppressed by geosmin. Surprisingly, the suppression is, however, only present at very low geosmin concentrations, and completely disappears at higher concentrations. We investigated the underlying mechanisms of the behavioural change at the level of the olfactory receptor neurons by means of electroantennography and at the level of the antennal lobe output via calcium imaging. Unusual effects were observed at both levels. The responses of the olfactory receptor neurons to mixtures of geosmin and the alarm pheromone component isoamyl acetate (IAA) were lower than to pure IAA, suggesting an interaction of both compounds at the olfactory receptor level. In the antennal lobe, the neuronal representation of geosmin showed a glomerular activation that decreased with increasing concentration, correlating well with the concentration dependence of the behaviour. Computational modelling of odour transduction and odour coding in the antennal lobe suggests that a broader than usual activation of different olfactory receptor types by geosmin in combination with lateral inhibition in the antennal lobe could lead to the observed non-monotonic increasing-decreasing responses to geosmin and thus underlie the specificity of the behavioural response to low geosmin concentrations.

Effects of Mechanosensory Input on the Tracking of Pulsatile Odor Stimuli by Moth Antennal Lobe Neurons

Air turbulence ensures that in a natural environment insects tend to encounter odor stimuli in a pulsatile fashion. The frequency and duration of odor pulses varies with distance from the source, and hence successful mid-flight odor tracking requires resolution of spatiotemporal pulse dynamics. This requires both olfactory and mechanosensory input (from wind speed), a form of sensory integration observed within the antennal lobe (AL). In this work, we employ a model of the moth AL to study the effect of mechanosensory input on AL responses to pulsatile stimuli; in particular, we examine the ability of model neurons to: (1) encode the temporal length of a stimulus pulse; (2) resolve the temporal dynamics of a high frequency train of brief stimulus pulses. We find that AL glomeruli receiving olfactory input are adept at encoding the temporal length of a stimulus pulse but less effective at tracking the temporal dynamics of a pulse train, while glomeruli receiving mechanosensory input but little olfactory input can efficiently track the temporal dynamics of high frequency pulse delivery but poorly encode the duration of an individual pulse. Furthermore, we show that stronger intrinsic small-conductance calcium-dependent potassium (SK) currents tend to skew cells toward being better trackers of pulse frequency, while weaker SK currents tend to entail better encoding of the temporal length of individual pulses. We speculate a possible functional division of labor within the AL, wherein, for a particular odor, glomeruli receiving strong olfactory input exhibit prolonged spiking responses that facilitate detailed discrimination of odor features, while glomeruli receiving mechanosensory input (but little olfactory input) serve to resolve the temporal dynamics of brief, pulsatile odor encounters. Finally, we discuss how this hypothesis extends to explaining the functional significance of intraglomerular variability in observed phase II response patterns of AL neurons.