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• W2009156797 abstract "•Activating a single glomerulus recruits GABAergic interneurons in all glomeruli•The relative level of lateral inhibition in different glomeruli is odor invariant•Each glomerulus has a characteristic level of sensitivity to lateral inhibition•A single odor often activates glomeruli with high and low sensitivity to inhibition Odorant receptors in the periphery map precisely onto olfactory glomeruli (“coding channels”) in the brain. However, the odor tuning of a glomerulus is not strongly correlated with its spatial position. This raises the question of whether lateral inhibition between glomeruli is specific or nonspecific. Here we show that, in the Drosophila brain, focal activation of even a single glomerulus recruits GABAergic interneurons in all glomeruli. Moreover, the relative level of interneuron activity in different glomeruli is largely odor invariant. Although interneurons are recruited nonspecifically, glomeruli differ dramatically in their sensitivity to interneuron activity, and this is explained by their varying sensitivity to GABA. Interestingly, a stimulus is typically encoded in parallel by channels having high and low sensitivity to inhibition. Because lateral inhibition confers both costs and benefits, the brain might rely preferentially on “high” and “low” channels in different behavioral contexts. Odorant receptors in the periphery map precisely onto olfactory glomeruli (“coding channels”) in the brain. However, the odor tuning of a glomerulus is not strongly correlated with its spatial position. This raises the question of whether lateral inhibition between glomeruli is specific or nonspecific. Here we show that, in the Drosophila brain, focal activation of even a single glomerulus recruits GABAergic interneurons in all glomeruli. Moreover, the relative level of interneuron activity in different glomeruli is largely odor invariant. Although interneurons are recruited nonspecifically, glomeruli differ dramatically in their sensitivity to interneuron activity, and this is explained by their varying sensitivity to GABA. Interestingly, a stimulus is typically encoded in parallel by channels having high and low sensitivity to inhibition. Because lateral inhibition confers both costs and benefits, the brain might rely preferentially on “high” and “low” channels in different behavioral contexts. In some brain regions, a neuron’s preferred stimulus and its physical location are systematically related. In these “topographic” regions, neurons that are physically near each other often have similar tuning. Because most inhibitory interneurons act locally, inhibition in these brain regions occurs mainly between neurons whose activity is correlated (Kaas, 1997Kaas J.H. Topographic maps are fundamental to sensory processing.Brain Res. Bull. 1997; 44: 107-112Crossref PubMed Scopus (294) Google Scholar). Lateral inhibition in topographic networks allows neurons to encode finer details by removing the coarse (i.e., shared) components of their signals (Srinivasan et al., 1982Srinivasan M.V. Laughlin S.B. Dubs A. Predictive coding: a fresh view of inhibition in the retina.Proc. R. Soc. Lond. B Biol. Sci. 1982; 216: 427-459Crossref PubMed Scopus (690) Google Scholar). It also reduces redundancy, thereby conserving metabolic resources (Barlow, 1961Barlow H.G. Possible principles underlying the transformation of sensory messages.in: Rosenblith W.A. Sensory Communication. MIT Press, Cambridge, MA1961: 217-234Google Scholar). However, many brain regions are non-topographic (or only weakly topographic), where neighboring neurons can have very different stimulus preferences (Bandyopadhyay et al., 2010Bandyopadhyay S. Shamma S.A. Kanold P.O. Dichotomy of functional organization in the mouse auditory cortex.Nat. Neurosci. 2010; 13: 361-368Crossref PubMed Scopus (172) Google Scholar, Ohki et al., 2005Ohki K. Chung S. Ch’ng Y.H. Kara P. Reid R.C. Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex.Nature. 2005; 433: 597-603Crossref PubMed Scopus (866) Google Scholar, Redish et al., 2001Redish A.D. Battaglia F.P. Chawla M.K. Ekstrom A.D. Gerrard J.L. Lipa P. Rosenzweig E.S. Worley P.F. Guzowski J.F. McNaughton B.L. Barnes C.A. Independence of firing correlates of anatomically proximate hippocampal pyramidal cells.J. Neurosci. 2001; 21: RC134PubMed Google Scholar, Rothschild et al., 2010Rothschild G. Nelken I. Mizrahi A. Functional organization and population dynamics in the mouse primary auditory cortex.Nat. Neurosci. 2010; 13: 353-360Crossref PubMed Scopus (249) Google Scholar, Soucy et al., 2009Soucy E.R. Albeanu D.F. Fantana A.L. Murthy V.N. Meister M. Precision and diversity in an odor map on the olfactory bulb.Nat. Neurosci. 2009; 12: 210-220Crossref PubMed Scopus (237) Google Scholar, Stettler and Axel, 2009Stettler D.D. Axel R. Representations of odor in the piriform cortex.Neuron. 2009; 63: 854-864Abstract Full Text Full Text PDF PubMed Scopus (380) Google Scholar). In general, it is not clear to what extent lateral inhibitory connections are selective in non-topographic networks. An example of a non-topographic circuit is the brain’s first odor processing relay, the antennal lobe in insects and the olfactory bulb in vertebrates (Vosshall and Stocker, 2007Vosshall L.B. Stocker R.F. Molecular architecture of smell and taste in Drosophila.Annu. Rev. Neurosci. 2007; 30: 505-533Crossref PubMed Scopus (635) Google Scholar, Shepherd and Greer, 1998Shepherd G.M. Greer C.A. Olfactory bulb.in: Shepherd G.M. The Synaptic Organization of the Brain. Oxford University Press, New York1998: 159-203Google Scholar). Each coding channel (or glomerulus) in this circuit receives convergent projections from many olfactory receptor neurons (ORNs), all of which express the same odorant receptor. Within each glomerulus, ORNs synapse onto second-order neurons, each of which receives direct ORN input from just one glomerulus. Thus, each glomerulus defines a discrete processing channel. Although each glomerulus has a stereotyped location, the arrangement of glomeruli displays little or no topography—i.e., odor-evoked input to glomeruli that are physically near one another is no more correlated than the input to any random pair of glomeruli (Couto et al., 2005Couto A. Alenius M. Dickson B.J. Molecular, anatomical, and functional organization of the Drosophila olfactory system.Curr. Biol. 2005; 15: 1535-1547Abstract Full Text Full Text PDF PubMed Scopus (671) Google Scholar, Hallem and Carlson, 2006Hallem E.A. Carlson J.R. Coding of odors by a receptor repertoire.Cell. 2006; 125: 143-160Abstract Full Text Full Text PDF PubMed Scopus (834) Google Scholar, Soucy et al., 2009Soucy E.R. Albeanu D.F. Fantana A.L. Murthy V.N. Meister M. Precision and diversity in an odor map on the olfactory bulb.Nat. Neurosci. 2009; 12: 210-220Crossref PubMed Scopus (237) Google Scholar). Odors typically activate multiple ORN types, and the output of a glomerulus depends on its interactions with other coactivated glomeruli. In particular, glomeruli inhibit each other via inhibitory local interneurons (“lateral inhibition”). One fact relevant to lateral inhibition is that odor-evoked activity tends to be correlated across ORNs, meaning that an odor that strongly activates one ORN type typically elicits strong activity in many other ORN types (Haddad et al., 2010Haddad R. Weiss T. Khan R. Nadler B. Mandairon N. Bensafi M. Schneidman E. Sobel N. Global features of neural activity in the olfactory system form a parallel code that predicts olfactory behavior and perception.J. Neurosci. 2010; 30: 9017-9026Crossref PubMed Scopus (71) Google Scholar, Olsen et al., 2010Olsen S.R. Bhandawat V. Wilson R.I. Divisive normalization in olfactory population codes.Neuron. 2010; 66: 287-299Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar, Luo et al., 2010Luo S.X. Axel R. Abbott L.F. Generating sparse and selective third-order responses in the olfactory system of the fly.Proc. Natl. Acad. Sci. USA. 2010; 107: 10713-10718Crossref PubMed Scopus (93) Google Scholar). One proposed function of lateral inhibition is to reduce these correlations at the level of second-order neurons (Cleland, 2014Cleland T.A. Construction of odor representations by olfactory bulb microcircuits.Prog. Brain Res. 2014; 208: 177-203Crossref PubMed Scopus (31) Google Scholar, Wilson, 2013Wilson R.I. Early olfactory processing in Drosophila: mechanisms and principles.Annu. Rev. Neurosci. 2013; 36: 217-241Crossref PubMed Scopus (222) Google Scholar). An important outstanding question in olfaction is the degree of selectivity in lateral inhibition. In the olfactory bulb, the evidence for selective connectivity is mixed (Fantana et al., 2008Fantana A.L. Soucy E.R. Meister M. Rat olfactory bulb mitral cells receive sparse glomerular inputs.Neuron. 2008; 59: 802-814Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar, Luo and Katz, 2001Luo M. Katz L.C. Response correlation maps of neurons in the mammalian olfactory bulb.Neuron. 2001; 32: 1165-1179Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar, Willhite et al., 2006Willhite D.C. Nguyen K.T. Masurkar A.V. Greer C.A. Shepherd G.M. Chen W.R. Viral tracing identifies distributed columnar organization in the olfactory bulb.Proc. Natl. Acad. Sci. USA. 2006; 103: 12592-12597Crossref PubMed Scopus (148) Google Scholar). Physiological studies in the olfactory bulb have inferred lateral inhibitory connectivity indirectly, based on the premise that anti-correlated activity in two glomeruli reflects an inhibitory connection between them. This question can be addressed more directly in the Drosophila antennal lobe. The Drosophila antennal lobe is compact and genetically accessible, and the activity of inhibitory local neurons (LNs) can be optically monitored within each glomerulus (Ng et al., 2002Ng M. Roorda R.D. Lima S.Q. Zemelman B.V. Morcillo P. Miesenböck G. Transmission of olfactory information between three populations of neurons in the antennal lobe of the fly.Neuron. 2002; 36: 463-474Abstract Full Text Full Text PDF PubMed Scopus (375) Google Scholar, Silbering et al., 2008Silbering A.F. Okada R. Ito K. Galizia C.G. Olfactory information processing in the Drosophila antennal lobe: anything goes?.J. Neurosci. 2008; 28: 13075-13087Crossref PubMed Scopus (99) Google Scholar). Lateral inhibition in this circuit is known to play a key role in gain control (Olsen and Wilson, 2008Olsen S.R. Wilson R.I. Lateral presynaptic inhibition mediates gain control in an olfactory circuit.Nature. 2008; 452: 956-960Crossref PubMed Scopus (345) Google Scholar, Root et al., 2008Root C.M. Masuyama K. Green D.S. Enell L.E. Nässel D.R. Lee C.H. Wang J.W. A presynaptic gain control mechanism fine-tunes olfactory behavior.Neuron. 2008; 59: 311-321Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar) and may have other functions as well. Here we address two outstanding questions regarding interglomerular inhibition. First, how specific are inhibitory interactions between glomeruli? Previous studies have suggested that inhibition is sparse and specific (Girardin et al., 2013Girardin C.C. Kreissl S. Galizia C.G. Inhibitory connections in the honeybee antennal lobe are spatially patchy.J. Neurophysiol. 2013; 109: 332-343Crossref PubMed Scopus (22) Google Scholar, Ng et al., 2002Ng M. Roorda R.D. Lima S.Q. Zemelman B.V. Morcillo P. Miesenböck G. Transmission of olfactory information between three populations of neurons in the antennal lobe of the fly.Neuron. 2002; 36: 463-474Abstract Full Text Full Text PDF PubMed Scopus (375) Google Scholar), or pan-glomerular (Asahina et al., 2009Asahina K. Louis M. Piccinotti S. Vosshall L.B. A circuit supporting concentration-invariant odor perception in Drosophila.J. Biol. 2009; 8: 9Crossref PubMed Scopus (101) Google Scholar, Olsen et al., 2010Olsen S.R. Bhandawat V. Wilson R.I. Divisive normalization in olfactory population codes.Neuron. 2010; 66: 287-299Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar), or both (Sachse and Galizia, 2002Sachse S. Galizia C.G. Role of inhibition for temporal and spatial odor representation in olfactory output neurons: a calcium imaging study.J. Neurophysiol. 2002; 87: 1106-1117PubMed Google Scholar, Silbering and Galizia, 2007Silbering A.F. Galizia C.G. Processing of odor mixtures in the Drosophila antennal lobe reveals both global inhibition and glomerulus-specific interactions.J. Neurosci. 2007; 27: 11966-11977Crossref PubMed Scopus (161) Google Scholar, Silbering et al., 2008Silbering A.F. Okada R. Ito K. Galizia C.G. Olfactory information processing in the Drosophila antennal lobe: anything goes?.J. Neurosci. 2008; 28: 13075-13087Crossref PubMed Scopus (99) Google Scholar). Some individual LNs innervate all glomeruli, whereas others innervate just a subset of glomeruli, so any of these scenarios is possible (Chou et al., 2010Chou Y.H. Spletter M.L. Yaksi E. Leong J.C. Wilson R.I. Luo L. Diversity and wiring variability of olfactory local interneurons in the Drosophila antennal lobe.Nat. Neurosci. 2010; 13: 439-449Crossref PubMed Scopus (225) Google Scholar, Seki et al., 2010Seki Y. Rybak J. Wicher D. Sachse S. Hansson B.S. Physiological and morphological characterization of local interneurons in the Drosophila antennal lobe.J. Neurophysiol. 2010; 104: 1007-1019Crossref PubMed Scopus (102) Google Scholar, Okada et al., 2009Okada R. Awasaki T. Ito K. Gamma-aminobutyric acid (GABA)-mediated neural connections in the Drosophila antennal lobe.J. Comp. Neurol. 2009; 514: 74-91Crossref PubMed Scopus (107) Google Scholar). Second, are all glomeruli equally sensitive to the effects of LN activation? Glomeruli are differentially innervated by individual inhibitory LNs (Chou et al., 2010Chou Y.H. Spletter M.L. Yaksi E. Leong J.C. Wilson R.I. Luo L. Diversity and wiring variability of olfactory local interneurons in the Drosophila antennal lobe.Nat. Neurosci. 2010; 13: 439-449Crossref PubMed Scopus (225) Google Scholar). Glomeruli also express variable levels of GABA receptor and show variable responses to a synthetic GABAB agonist (Root et al., 2008Root C.M. Masuyama K. Green D.S. Enell L.E. Nässel D.R. Lee C.H. Wang J.W. A presynaptic gain control mechanism fine-tunes olfactory behavior.Neuron. 2008; 59: 311-321Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar). In principle, either mechanism could produce variations in sensitivity to LN activation, but this has not been investigated. In this study, we find that the recruitment of inhibition is relatively nonspecific, and indeed, activating a single glomerulus recruits LN activity in all glomeruli. Nonetheless, glomeruli vary dramatically in their sensitivity to LN activation, i.e., their “inhibitability.” We propose that this organization allows some channels to realize the benefits of lateral inhibition, while allowing other channels to remain relatively immune from the costs of lateral inhibition—namely, noise and ambiguity. These results have broad relevance for how population diversity within a circuit can resolve competing constraints on neural processing. We began by asking whether inhibitory interactions between glomeruli are specific. We selected odor stimuli that excite only one ORN type, and we asked how the spatial pattern of activity in GABAergic LNs depends on the identity of the glomerulus that is receiving direct ORN input. If inhibition is sparse and glomerulus specific, the glomerular pattern of LN activity should be different for odors that activate different ORN types, and focal stimulation should in principle be the clearest way to reveal this. We identified eight odor stimuli that should drive activity primarily in a single ORN type, which we call “private” odor stimuli (Hallem and Carlson, 2006Hallem E.A. Carlson J.R. Coding of odors by a receptor repertoire.Cell. 2006; 125: 143-160Abstract Full Text Full Text PDF PubMed Scopus (834) Google Scholar, Olsen et al., 2010Olsen S.R. Bhandawat V. Wilson R.I. Divisive normalization in olfactory population codes.Neuron. 2010; 66: 287-299Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar, Schlief and Wilson, 2007Schlief M.L. Wilson R.I. Olfactory processing and behavior downstream from highly selective receptor neurons.Nat. Neurosci. 2007; 10: 623-630Crossref PubMed Scopus (114) Google Scholar). To visualize the pattern of ORN input evoked by each stimulus, we expressed the genetically encoded calcium indicator GCaMP3 (Tian et al., 2009Tian L. Hires S.A. Mao T. Huber D. Chiappe M.E. Chalasani S.H. Petreanu L. Akerboom J. McKinney S.A. Schreiter E.R. et al.Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators.Nat. Methods. 2009; 6: 875-881Crossref PubMed Scopus (1456) Google Scholar) in ORNs under the control of the Gal4-UAS system. We then used in vivo two-photon microscopy to image odor-evoked signals in ORN axons terminating in the antennal lobe. As expected, each private odor stimulus elicited a fluorescence increase at the position corresponding to its cognate glomerulus (Figures 1A and 1B ). In some experiments, one or two additional glomeruli were also weakly activated, but this was unusual. To visualize LN activity elicited by focal ORN input, we expressed GCaMP3 in a large subset of GABAergic LNs using the NP3056-Gal4 driver (Chou et al., 2010Chou Y.H. Spletter M.L. Yaksi E. Leong J.C. Wilson R.I. Luo L. Diversity and wiring variability of olfactory local interneurons in the Drosophila antennal lobe.Nat. Neurosci. 2010; 13: 439-449Crossref PubMed Scopus (225) Google Scholar) and imaged calcium signals in LN neurites. The NP3056-Gal4 driver labels between 50 and 60 LNs in the antennal lobe, and most individual LNs in this population innervate most or all glomeruli (Chou et al., 2010Chou Y.H. Spletter M.L. Yaksi E. Leong J.C. Wilson R.I. Luo L. Diversity and wiring variability of olfactory local interneurons in the Drosophila antennal lobe.Nat. Neurosci. 2010; 13: 439-449Crossref PubMed Scopus (225) Google Scholar), which is typical of GABAergic LNs in general (Chou et al., 2010Chou Y.H. Spletter M.L. Yaksi E. Leong J.C. Wilson R.I. Luo L. Diversity and wiring variability of olfactory local interneurons in the Drosophila antennal lobe.Nat. Neurosci. 2010; 13: 439-449Crossref PubMed Scopus (225) Google Scholar, Seki et al., 2010Seki Y. Rybak J. Wicher D. Sachse S. Hansson B.S. Physiological and morphological characterization of local interneurons in the Drosophila antennal lobe.J. Neurophysiol. 2010; 104: 1007-1019Crossref PubMed Scopus (102) Google Scholar, Okada et al., 2009Okada R. Awasaki T. Ito K. Gamma-aminobutyric acid (GABA)-mediated neural connections in the Drosophila antennal lobe.J. Comp. Neurol. 2009; 514: 74-91Crossref PubMed Scopus (107) Google Scholar). Thus, the calcium signal in each glomerulus represents the pooled activity of many LNs, and the signal in every glomerulus originates from mostly the same group of individual LNs. We found that each private odor elicited LN activity in all glomeruli (Figures 1C and 1D and data not shown). Moreover, similar spatial patterns of activity were elicited by different odors. This outcome was observed in two independent rounds of experiments performed with different odor stimulus sets, each containing four private odors (odor set 1 and odor set 2). Similar results were also observed with a second Gal4 driver that labels about 25–30 GABAergic LNs (GH298-Gal4; Figure S1). These two LN drivers are expressed in large but mostly non-overlapping subsets of LNs. Together, they cover 8 of the 9 major morphological types of GABAergic LNs, including both pan-glomerular LNs and LNs with selective glomerular innervation patterns (Chou et al., 2010Chou Y.H. Spletter M.L. Yaksi E. Leong J.C. Wilson R.I. Luo L. Diversity and wiring variability of olfactory local interneurons in the Drosophila antennal lobe.Nat. Neurosci. 2010; 13: 439-449Crossref PubMed Scopus (225) Google Scholar). Both drivers and all odors produced essentially the same global pattern of LN activity. To evaluate the similarity across brains in the spatial pattern of LN activity, we computed the average response across odors for each brain and measured the relative level of LN calcium signal in different glomeruli in that average image (Figure 1E). This quantification showed that the relative level of LN activity varied about 3-fold across glomeruli, with each glomerulus exhibiting a characteristic level of activity in every brain. The differences between glomeruli in the average amount of odor-evoked LN calcium signal may reflect spatial heterogeneities in calcium entry, buffering, or extrusion across the branches of individual LNs. Although the spatial patterns of LN activity were relatively stimulus invariant, small differences were observed for some stimuli (Figures 1C and 1D). To search for putative odor-specific patterns of LN activity in an unbiased manner, we used principal component analysis (PCA). In each imaging plane, we performed PCA on the four images that were collected in the same experiment, one image for each odor. If all odors elicited the same pattern of activity, then almost all of the variance across odors would be explained by one “basis image” (i.e., the first principal component or PC1) that resembles the average across odors, and the remaining basis images (PC2 and upward) would simply capture noise. This prediction was largely true: PC1 captured the stereotyped and global spatial pattern evoked by all odors (Figures 2A and 2B ), and it accounted for most of the explainable variance in the data (Figure S2). However, PCA also pulled out three glomeruli that were modulated independently of other glomeruli. These three glomeruli are DA2, VL2a, and V. These are the cognate glomeruli for geosmin, phenylacetaldehyde, and CO2, respectively, and they each consistently emerged as PC2 in the appropriate position and imaging plane in the experiments that included these odors (odor set 2, Figure 2B). Thus, although all stimuli elicited a similar overall spatial pattern of LN activity, some private odor stimuli appeared to elicit additional activity in their cognate glomerulus. To test this idea directly, we quantified the amount of LN activity in each of the eight glomeruli targeted by our “private” odors. As expected, we found that LN activity in DA2, VL2a, and V was significantly stronger when the stimulus was the cognate private odor for that glomerulus, as compared to other odors (Figure 2C). For all other glomeruli (DM4, VM7, VA6, DL1, and DL5), there was no significant difference between the level of LN activity elicited by their cognate private odor and other odors (Figure 2C). This analysis confirms the results of the unbiased PCA search: some stimuli elicit additional intraglomerular inhibition, as well as recruiting lateral inhibition to all other glomeruli. In addition, these results indicate that PCA can successfully identify glomeruli that are recruited in an odor-specific manner. Notably, no other individual glomeruli, or subsets of glomeruli, were observed in any principal components. Thus, although PCA is demonstrably able to identify single glomeruli that are modulated in an odor-specific manner, it does not identify any additional glomeruli where LN activity is comodulated. This analysis argues that there are no strong inhibitory subnetworks linking specific groups of glomeruli. Next, we asked whether these results generalize across a range of odor concentrations. We tested a family of concentrations for several odors. In each case, we found that the relative level of LN activity in different glomeruli was similar across odor concentrations. However, the overall level of LN activity grew with increasing concentration (Figures 3A and 3C ). Higher concentrations activate more ORN types and also drive higher spike rates in activated ORNs (Hallem and Carlson, 2006Hallem E.A. Carlson J.R. Coding of odors by a receptor repertoire.Cell. 2006; 125: 143-160Abstract Full Text Full Text PDF PubMed Scopus (834) Google Scholar). Both mechanisms are likely to contribute to the overall increase in LN activity. When we averaged LN activity across the antennal lobe and plotted this against the logarithm of the odor-evoked field potential recorded from ORNs (Figure 3B), we observed a linear relationship for all odors (Figure 3D). Because the ORN field potential scales linearly with the total number of ORN spikes (Olsen et al., 2010Olsen S.R. Bhandawat V. Wilson R.I. Divisive normalization in olfactory population codes.Neuron. 2010; 66: 287-299Abstract Full Text Full Text PDF PubMed Scopus (297) Google Scholar), we can infer that LN activity scales with the logarithm of total ORN spike rate. Interestingly, not all odors were equally efficient at recruiting LN activity, even when they evoked equal levels of total ORN activity. For example, 10−4 pentyl acetate and 10−6 E2-hexenal elicited similar levels of total ORN activity (Figure 3B). However, 10−4 pentyl acetate elicited stronger overall LN activity than did 10−6 E2-hexenal (Figures 3A and 3C–3E). This difference may reflect the fact that the pentyl acetate stimulus elicits ORN spiking that is distributed across more ORN types (Hallem and Carlson, 2006Hallem E.A. Carlson J.R. Coding of odors by a receptor repertoire.Cell. 2006; 125: 143-160Abstract Full Text Full Text PDF PubMed Scopus (834) Google Scholar). Alternatively, or in addition, some ORN or PN types may make particularly strong synapses onto LNs. In sum, these results show that ORN input to a single glomerulus can recruit LN activity globally in all glomeruli and that the relative level of LN activity across most glomeruli is similar for all odor stimuli. Stimulation of some ORN types elicits additional LN activity in their target glomeruli. Finally, the level of LN activity in each glomerulus scales with the logarithm of total ORN firing rate. Taken together, these results indicate that lateral inhibition in the antennal lobe is broadly recruited by inputs pooled across most glomeruli and argue against selective interactions between neurons corresponding to specific subnetworks of glomeruli. We next turned our attention from the recruitment of LNs to the consequences of LN activation. In particular, we asked whether LN activation has different effects on different antennal lobe projection neurons (PNs), the second-order neurons of the olfactory system. To activate LNs, we used an optogenetic method rather than odor stimuli, an approach that confers several advantages. First, by not using odors, we avoided eliciting varying levels of excitation to different PNs, a situation that would confound our measurements of inhibition in PNs. Second, optogenetics allows for the direct, robust, and scalable activation of LNs. We expressed the light-activated cation channel channelrhodopsin-2 (ChR2) in a large subset of LNs under the control of NP3056-Gal4. Whole-cell recordings from LNs that express ChR2 confirmed that LN spike rates rise with increasing light intensity, and light evokes no response in ChR2-negative LNs (Figure S3). Calcium imaging of ChR2-mediated LN activation revealed that interleaved light and odor stimuli elicit essentially identical spatial patterns of LN activity (Figures 4A and 4B ). Thus, optogenetic LN activation serves as a convenient stand-in for odor-evoked LN activation. To measure the consequences of LN activation, we monitored spontaneous excitatory postsynaptic currents (sEPSCs) in PNs, which arise from spontaneous spiking in ORNs (Figure 4C; Kazama and Wilson, 2008Kazama H. Wilson R.I. Homeostatic matching and nonlinear amplification at identified central synapses.Neuron. 2008; 58: 401-413Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, Kazama and Wilson, 2009Kazama H. Wilson R.I. Origins of correlated activity in an olfactory circuit.Nat. Neurosci. 2009; 12: 1136-1144Crossref PubMed Scopus (100) Google Scholar). Spontaneous EPSCs are a sensitive measure of inhibition because the primary locus of GABAergic inhibition is at ORN axon terminals, with a more minor role for inhibition at PN dendrites (Olsen and Wilson, 2008Olsen S.R. Wilson R.I. Lateral presynaptic inhibition mediates gain control in an olfactory circuit.Nature. 2008; 452: 956-960Crossref PubMed Scopus (345) Google Scholar, Root et al., 2008Root C.M. Masuyama K. Green D.S. Enell L.E. Nässel D.R. Lee C.H. Wang J.W. A presynaptic gain control mechanism fine-tunes olfactory behavior.Neuron. 2008; 59: 311-321Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar). We note that stimulating GABAergic LNs can recruit not only lateral inhibition, but also lateral excitation, because GABAergic LNs are electrically coupled to specialized cells that also couple to PNs (Huang et al., 2010Huang J. Zhang W. Qiao W. Hu A. Wang Z. Functional connectivity and selective odor responses of excitatory local interneurons in Drosophila antennal lobe.Neuron. 2010; 67: 1021-1033Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar, Yaksi and Wilson, 2010Yaksi E. Wilson R.I. Electrical coupling between olfactory glomeruli.Neuron. 2010; 67: 1034-1047Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar). To eliminate this confound, we conducted these experiments in a genetic background that blocks these electrical connections (shakB mutant; Yaksi and Wilson, 2010Yaksi E. Wilson R.I. Electrical coupling between olfactory glomeruli.Neuron. 2010; 67: 1034-1047Abstract Full Text Full Text PDF PubMed Scopus (132) Google Scholar). We observed that optogenetic activation of LNs suppressed sEPSCs in most PNs, and this effect was blocked by GABA receptor antagonists (Figures 4C and 4D). In PNs, increasing light intensity increased the suppression of" @default.
• W2009156797 created "2016-06-24" @default.
• W2009156797 creator A5012234077 @default.
• W2009156797 creator A5045622899 @default.
• W2009156797 date "2015-02-01" @default.
• W2009156797 modified "2023-10-12" @default.
• W2009156797 title "Simultaneous Encoding of Odors by Channels with Diverse Sensitivity to Inhibition" @default.
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