Shallow networks run deep: Peripheral preprocessing facilitates odor classification.

The mammalian brain implements sophisticated sensory processing algorithms along multilayered ('deep') neural-networks. Strategies that insects use to meet similar computational demands, while relying on smaller nervous systems with shallow architectures, remain elusive. Using Drosophila as a model, we uncover the algorithmic role of odor preprocessing by a shallow network of compartmentalized olfactory receptor neurons. Each compartment operates as a ratiometric unit for specific odor-mixtures. This computation arises from a simple mechanism: electrical coupling between two differently-sized neurons. We demonstrate that downstream synaptic connectivity is shaped to optimally leverage amplification of a hedonic value signal in the periphery. Furthermore, peripheral preprocessing is shown to markedly improve novel odor classification in a higher brain center. Together, our work highlights a far-reaching functional role of the sensory periphery for downstream processing. By elucidating the implementation of powerful computations by a shallow network, we provide insights into general principles of efficient sensory processing algorithms.

Valence opponency in peripheral olfactory processing.

A hallmark of complex sensory systems is the organization of neurons into functionally meaningful maps, which allow for comparison and contrast of parallel inputs via lateral inhibition. However, it is unclear whether such a map exists in olfaction. Here, we address this question by determining the organizing principle underlying the stereotyped pairing of olfactory receptor neurons (ORNs) in Drosophila sensory hairs, wherein compartmentalized neurons inhibit each other via ephaptic coupling. Systematic behavioral assays reveal that most paired ORNs antagonistically regulate the same type of behavior. Such valence opponency is relevant in critical behavioral contexts including place preference, egg laying, and courtship. Odor-mixture experiments show that ephaptic inhibition provides a peripheral means for evaluating and shaping countervailing cues relayed to higher brain centers. Furthermore, computational modeling suggests that this organization likely contributes to processing ratio information in odor mixtures. This olfactory valence map may have evolved to swiftly process ethologically meaningful odor blends without involving costly synaptic computation.

An ammonium transporter is a non-canonical olfactory receptor for ammonia.

Numerous hematophagous insects are attracted to ammonia, a volatile released in human sweat and breath.1-3 Low levels of ammonia also attract non-biting insects such as the genetic model organism Drosophila melanogaster and several species of agricultural pests.4,5 Two families of ligand-gated ion channels function as olfactory receptors in insects,6-10 and studies have linked ammonia sensitivity to a particular olfactory receptor in Drosophila.5,11,12 Given the widespread importance of ammonia to insect behavior, it is surprising that the genomes of most insects lack an ortholog of this gene.6 Here, we show that canonical olfactory receptors are not necessary for responses to ammonia in Drosophila. Instead, we demonstrate that a member of the ancient electrogenic ammonium transporter family, Amt, is likely a new type of olfactory receptor. We report two hitherto unidentified olfactory neuron populations that mediate neuronal and behavioral responses to ammonia in Drosophila. Their endogenous ammonia responses are lost in Amt mutant flies, and ectopic expression of either Drosophila or Anopheles Amt confers ammonia sensitivity. These results suggest that Amt is the first transporter known to function as an olfactory receptor in animals and that its function may be conserved across insect species.

Neuronal Compartmentalization: A Means to Integrate Sensory Input at the Earliest Stage of Information Processing?

In numerous peripheral sense organs, external stimuli are detected by primary sensory neurons compartmentalized within specialized structures composed of cuticular or epithelial tissue. Beyond reflecting developmental constraints, such compartmentalization also provides opportunities for grouped neurons to functionally interact. Here, the authors review and illustrate the prevalence of these structural units, describe characteristics of compartmentalized neurons, and consider possible interactions between these cells. This article discusses instances of neuronal crosstalk, examples of which are observed in the vertebrate tastebuds and multiple types of arthropod chemosensory hairs. Particular attention is paid to insect olfaction, which presents especially well-characterized mechanisms of functional, cross-neuronal interactions. These examples highlight the potential impact of peripheral processing, which likely contributes more to signal integration than previously considered. In surveying a wide variety of structural units, it is hoped that this article will stimulate future research that determines whether grouped neurons in other sensory systems can also communicate to impact information processing.

Amplification of Drosophila Olfactory Responses by a DEG/ENaC Channel.

Insect olfactory receptors operate as ligand-gated ion channels that directly transduce odor stimuli into electrical signals. However, in the absence of any known intermediate transduction steps, it remains unclear whether and how these ionotropic inputs are amplified in olfactory receptor neurons (ORNs). Here, we find that amplification occurs in the Drosophila courtship-promoting ORNs through Pickpocket 25 (PPK25), a member of the degenerin/epithelial sodium channel family (DEG/ENaC). Pharmacological and genetic manipulations indicate that, in Or47b and Ir84a ORNs, PPK25 mediates Ca2+-dependent signal amplification via an intracellular calmodulin-binding motif. Additionally, hormonal signaling upregulates PPK25 expression to determine the degree of amplification, with striking effects on male courtship. Together, these findings advance our understanding of sensory neurobiology by identifying an amplification mechanism compatible with ionotropic signaling. Moreover, this study offers new insights into DEG/ENaC activation by highlighting a novel means of regulation that is likely conserved across species.

Behavioral state modulates the ON visual motion pathway of Drosophila.

The behavioral state of an animal can dynamically modulate visual processing. In flies, the behavioral state is known to alter the temporal tuning of neurons that carry visual motion information into the central brain. However, where this modulation occurs and how it tunes the properties of this neural circuit are not well understood. Here, we show that the behavioral state alters the baseline activity levels and the temporal tuning of the first directionally selective neuron in the ON motion pathway (T4) as well as its primary input neurons (Mi1, Tm3, Mi4, Mi9). These effects are especially prominent in the inhibitory neuron Mi4, and we show that central octopaminergic neurons provide input to Mi4 and increase its excitability. We further show that octopamine neurons are required for sustained behavioral responses to fast-moving, but not slow-moving, visual stimuli in walking flies. These results indicate that behavioral-state modulation acts directly on the inputs to the directionally selective neurons and supports efficient neural coding of motion stimuli.

The Emergence of Directional Selectivity in the Visual Motion Pathway of Drosophila.

The perception of visual motion is critical for animal navigation, and flies are a prominent model system for exploring this neural computation. In Drosophila, the T4 cells of the medulla are directionally selective and necessary for ON motion behavioral responses. To examine the emergence of directional selectivity, we developed genetic driver lines for the neuron types with the most synapses onto T4 cells. Using calcium imaging, we found that these neuron types are not directionally selective and that selectivity arises in the T4 dendrites. By silencing each input neuron type, we identified which neurons are necessary for T4 directional selectivity and ON motion behavioral responses. We then determined the sign of the connections between these neurons and T4 cells using neuronal photoactivation. Our results indicate a computational architecture for motion detection that is a hybrid of classic theoretical models.