Functional diversity among sensory receptors in a Drosophila olfactory circuit

The ability of an animal to detect, discriminate, and respond to odors depends on the function of its olfactory receptor neurons (ORNs), which in turn depends ultimately on odorant receptors. To understand the diverse mechanisms used by an animal in olfactory coding and computation, it is essential to understand the functional diversity of its odor receptors. The larval olfactory system of Drosophila melanogaster contains 21 ORNs and a comparable number of odorant receptors whose properties have been examined in only a limited way. We systematically screened them with a panel of ∼500 odorants, yielding >10,000 receptor–odorant combinations. We identify for each of 19 receptors an odorant that excites it strongly. The responses elicited by each of these odorants are analyzed in detail. The odorants elicited little cross-activation of other receptors at the test concentration; thus, low concentrations of many of these odorants in nature may be signaled by a single ORN. The receptors differed dramatically in sensitivity to their cognate odorants. The responses showed diverse temporal dynamics, with some odorants eliciting supersustained responses. An intriguing question in the field concerns the roles of different ORNs and receptors in driving behavior. We found that the cognate odorants elicited behavioral responses that varied across a broad range. Some odorants elicited strong physiological responses but weak behavioral responses or weak physiological responses but strong behavioral responses.The olfactory system of the Drosophila larva achieves remarkable function with minimal structure. It detects and responds to spatial and temporal gradients of odorants, transforming chemical information into navigation via an elegant repertoire of head sweeps, runs, and turns (1–3). Its sophisticated function is based on the activities of 21 olfactory receptor neurons (ORNs), which innervate the dorsal organ of the head and send axons to the antennal lobe of the brain (4). The activities of the ORNs are in turn based on the responses of odor receptors (Ors). Thus, to understand the molecular basis of larval olfactory navigation, it is necessary to understand the function of the receptors.ORNs together express 25 members of the Or family of odor receptors and the Orco coreceptor (5–8). In each ORN, an Or and Orco together form a ligand-gated ion channel (9–11). Most ORNs express a single Or, although one ORN coexpresses Or94a and Or94b and another ORN coexpresses Or33b and Or47a (7). The significance of this coexpression remains speculative, but the response profiles of some coexpressed adult Ors are additive (12).The responses of the larval Or repertoire to a limited odorant panel was previously examined in an in vivo expression system known as the empty neuron system (8, 13). With the use of this system, 21 of the larval Ors were found to be functional. However, studies of the larval Or repertoire have been limited not only in the number of odorants examined, but also in their consideration of receptor sensitivity, temporal dynamics, and roles in driving olfactory behavior.An intriguing question in the biology of a sensory system concerns the equivalency of its primary sensory neurons in driving behavioral output. A priori, activation of different sensory neurons could drive equivalent behavioral responses, particularly in a simple sensory system. Alternatively, different neurons might drive different behavioral responses, particularly if connectivity and downstream processing are complex, as in the olfactory systems of mammals and adult flies (14–16). In Drosophila, much less is known about olfactory processing in the larva than in the adult.One approach to examining the role of individual ORNs is to drive different individual neurons in a WT olfactory system with odorants, their natural stimuli, which activate them specifically.Here we carry out a screen of all 21 functional larval Ors to a panel of ∼500 diverse odorants. For each of 19 receptors, we identify an odorant that excites it strongly. These odorants showed little cross-activation of other receptors in a physiological test. The receptors differed dramatically in sensitivity to their most effective odorants. The temporal dynamics of responses exhibit great variation as well, with some showing supersustained responses. The odorants drove behavioral responses that varied across a broad continuum. Some odorants drove weak physiological responses and strong behavioral responses, or strong physiological responses and weak behavioral responses.