Lateral presynaptic inhibition mediates gain control in an olfactory circuit

Abstract

SUMMARYOlfactory signals are transduced by a large family of odorant receptor proteins, each of which corresponds to a unique glomerulus in the first olfactory relay of the brain. Cross-talk between glomeruli has been proposed to be important in olfactory processing, but it is not clear how these interactions shape the odor responses of second-order neurons. In the Drosophila antennal lobe (a region analogous to the vertebrate olfactory bulb), we selectively remove most inter-glomerular input to identified second-order olfactory neurons. We find this broadens the odor tuning of these neurons, implying that inter-glomerular inhibition dominates over inter-glomerular excitation. The strength of this inhibitory signal scales with total feedforward input to the entire antennal lobe, and has similar tuning in different glomeruli. A substantial portion of this inter-glomerular inhibition acts at a presynaptic locus, and our results imply this is mediated by both GABA A and GABA B receptors on the same nerve terminal.A sensory stimulus generally triggers activity in multiple neural processing channels, each of which carries information about some feature of that stimulus. The concept of a processing channel has a particularly clear anatomical basis in the first relay of the olfactory system, which is typically divided into glomerular compartments. Each glomerulus receives input from many first-order olfactory receptor neurons (ORNs), all of which express the same odorant receptor. Each second-order neuron receives direct ORN input from a single glomerulus, and thus all the first-and second-order neurons corresponding to a glomerulus constitute a discrete processing channel. An odorant typically triggers activity in multiple glomeruli, and local interneurons that interconnect glomeruli provide a substrate for cross-talk between channels.The Drosophila antennal lobe is a favored model for investigating olfactory processing because it contains only ~50 glomeruli 1 , each of which corresponds to an identified type of ORN and an identified type of postsynaptic projection neuron (PN) 2-5. Several recent studies of the Drosophila antennal lobe have produced divergent views of the relative importance of interglomerular connections. One model proposes that PN odor responses are almost completely determined by feedforward excitation6 , 7. This model ascribes little importance to cross-talk between glomerular processing channels. An alternative model proposes that inter-glomerular connections make an important contribution to shaping PN odor responses8 -12 . However, thisCorrespondence and requests for materials should be addressed to R.I.W. (rachel_wilson@hms.harvard.edu). Full Methods are available in the online version of the paper at www.nature.com/nature.Supplementary Information is linked to the online version of the paper at www.nature.com/nature. A figure summarizing the main result of this paper is available in Supplementary Information. . This could reflect a purely intra-glomerular nonlinear process, such as short-term...

Olfaction in vector-host interactions

“…In A. mellifera and M. sexta, however, physiological evidence supports a different model in which a substantial component of the lateral inhibition seems to act to sharpen the tuning curve of PNs rather than the ORN output, creating a more restricted spatial pattern of output from the odour-activated AL glomeruli (Christensen et al 1998, Sachse and Galizia 2002, Waldrop et al 1987. Evidence for a similar, but minor, component in D. melanogaster is available, but the functional implication of this arrangement is yet unknown (Olsen and Wilson 2008).…”

“…Although results emanating from these studies have expanded our knowledge about the neural mechanisms that shape the PN odour responses, it is important to acknowledge that these results may not directly transfer to the olfactory systems of other insects (reviewed by . A growing body of evidence, however, favours an interaction of interglomerular, or lateral, inhibitory connections between the processing channels in all insect species studied (Christensen et al 1998, Olsen and Wilson 2008, Sachse and Galizia 2002, Waldrop et al 1987. Lateral inhibition, through GABAergic LNs acting on both ORNs and PNs, is supported by ultrastructural analysis of their synaptic wiring (Boeckh and Tolbert 1993, Distler and Boeckh 1996, 1997a,b, Malun et al 1991a.…”

“…Lateral inhibition, through GABAergic LNs acting on both ORNs and PNs, is supported by ultrastructural analysis of their synaptic wiring (Boeckh and Tolbert 1993, Distler and Boeckh 1996, 1997a,b, Malun et al 1991a. Recent evidence from D. melanogaster suggests that a significant component of the lateral inhibition is directed towards ORNs (Olsen and Wilson 2008). The functional significance of this is that lateral inhibition mediates a gain control in the olfactory system by suppressing strong and redundant responses.…”

“…Accumulating evidence over the last few years from different insects, however, emphasises that LNs that tend to have broad multiglomerular ramifications ( Figure 7A), and thus provide a scaffold for crosstalk between channels, play a major role in shaping the output response of the processing channels (reviewed by , see also Bhandawat et al 2007, Olsen and Wilson 2008, Olsen et al 2007, Root et al 2007, Shang et al 2007, Wilson and Laurent 2005. In addition, intraglomerular events appear to have a significant influence on these processes (Bhandawat et al 2007, Christensen et al 2000, Kazama and Wilson 2008, Olsen and Wilson 2008, Wilson et al 2004). …”

Influence of blood meal on the responsiveness of olfactory receptor neurons in antennal sensilla trichodea of the yellow fever mosquito, Aedes aegypti

“…Indeed, it is perhaps not surprising to find ORN types in which 23 volatile sensitivity and selectivity do not change in response to a blood meal. These blood 1 meal insensitive sensory neurons provide a consistent baseline between two physiological 2 states that will allow the primary olfactory centre, the antennal lobe and in particular the 3 projection neurons, to highlight those neurons which have changed their sensitivity with 4 the altered physiological state (Kazama and Wilson, 2008; Olsen and Wilson, 2008). 5 Therefore, the conservation of ORN function in many sensillum types would in fact be 6 predicted.…”