Functional diversity among sensory receptors in a Drosophila olfactory circuit

Abstract

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.T he 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, tempor...

The chemical ecology of the fly

“…Diacetyl -formed from acetaldehyde -is the primary agonist of Or92a [10]. Acetalgenerated from the reaction of acetaldehyde with ethanol -is the key ligand of Or42b [11 ], whereas Or9a (and to a lesser extent Or92a) detects acetoin and 2,3-butanediol -reduction products of acetaldehyde [10,12]. The combined activation of these receptors would inform flies with a high degree of certainty that a fermenting, sugar-rich substrate has been located.…”

“…However, not all toxic microbes produce geosmin, and though no additional pathways with the function of detecting harmful microbes have so far been identified, a few other receptors might serve a similar purpose. Or33b is primarily activated by the widespread bacterial volatile 2,5-dimethylpyrazine, which is also produced by many entomopathogenic bacteria [11 ]. A role in mediating avoidance is also indicated by the observation that activation of Or33b in larvae triggers repulsion [41] and moreover, that Or33b neurons in adults target a glomerulus mediating aversive behavior [15].…”

Chemicals and chemoreceptors: ecologically relevant signals driving behavior in Drosophila

“…Furthermore, ORCO's expression is necessary both in adults and in larvae for electrophysiological and behavioral responses to several odorants, demonstrating that ORCO is an essential coreceptor for all the ORs (Larsson et al, 2004). By using a mutant antennal neuron that lacks its endogenous chemoreceptors (the "empty neuron" system; Dobritsa et al, 2003), the group of Carlson performed extensive electrophysiological characterizations of ORs responsiveness toward relevant food-derived odorants, both in the adult antenna and the larval olfactory system (Hallem et al, 2004;Hallem and Carlson, 2006;Kreher et al, 2008;Mathew et al, 2013). Individual receptors range along a continuum from narrowly to broadly tuned although, in general, reducing odor concentration reduces the number of ORs activated (Hallem and Carlson, 2006).…”

“…In contraposition to the extensive analysis of electrophysiological responses at the periphery, little is known about the relevance of specific ORs in driving behavior. In larvae, some odors weakly activate ORs but trigger strong behavioral responses and, on the contrary, other odors can strongly activate ORs but elicit weak behavioral responses (Mathew et al, 2013;Grewal et al, 2014); this highlights that odor coding in higherolfactory centers is a relevant process that modulates odor-trigger behaviors.…”

Compound valence is conserved in binary odor mixtures in Drosophila melanogaster

“…However, to conclusively answer these questions and to further dissect the neural mechanisms underlying the evaluation of chemical signals, it will be crucial to assign valence weights to the physiological activity of individual processing channels. This goal can be achieved by artificial activation of individual OSN types through targeted expression of light-gated ion channels (Bellmann et al, 2010) or by the use of low odor concentrations (Mathew et al, 2013), i.e. concentrations at which only single OSN channels become activated.…”