Non-synaptic interactions between olfactory receptor neurons, a possible key feature of odor processing in flies

When flies explore their environment, they encounter odors in complex, highly intermittent plumes. To navigate a plume and, for example, find food, they must solve several challenges, including reliably identifying mixtures of odorants and their intensities, and discriminating odorant mixtures emanating from a single source from odorants emitted from separate sources and just mixing in the air. Lateral inhibition in the antennal lobe is commonly understood to help solving these challenges. With a computational model of the Drosophila olfactory system, we analyze the utility of an alternative mechanism for solving them: Non-synaptic (“ephaptic”) interactions (NSIs) between olfactory receptor neurons that are stereotypically co-housed in the same sensilla. We find that NSIs improve mixture ratio detection and plume structure sensing and do so more efficiently than the traditionally considered mechanism of lateral inhibition in the antennal lobe. The best performance is achieved when both mechanisms work in synergy. However, we also found that NSIs decrease the dynamic range of co-housed ORNs, especially when they have similar sensitivity to an odorant. These results shed light, from a functional perspective, on the role of NSIs, which are normally avoided between neurons, for instance by myelination.

Ir76b is a Co-receptor for Amine Responses in Drosophila Olfactory Neurons

Two large families of olfactory receptors, the Odorant Receptors (ORs) and Ionotropic Receptors (IRs), mediate responses to most odors in the insect olfactory system. Individual odorant binding “tuning” OrX receptors are expressed by olfactory neurons in basiconic and trichoid sensilla and require the co-receptor Orco. The situation for IRs is more complex. Different tuning IrX receptors are expressed by olfactory neurons in coeloconic sensilla and rely on either the Ir25a or Ir8a co-receptors; some evidence suggests that Ir76b may also act as a co-receptor, but its function has not been systematically examined. Surprisingly, recent data indicate that nearly all coeloconic olfactory neurons co-express Ir25a, Ir8a, and Ir76b. Here, we demonstrate that Ir76b and Ir25a function together in all amine-sensing olfactory receptor neurons. In most neurons, loss of either co-receptor abolishes amine responses. In contrast, amine responses persist in the absence of Ir76b or Ir25a in ac1 sensilla but are lost in a double mutant. We show that responses mediated by acid-sensing neurons do not require Ir76b, despite their expression of this co-receptor. Our study also demonstrates that one population of coeloconic olfactory neurons exhibits Ir76b/Ir25a-dependent and Orco-dependent responses to distinct odorants. Together, our data establish the role of Ir76b as a bona fide co-receptor, which acts in partnership with Ir25a. Given that these co-receptors are among the most highly conserved olfactory receptors and are often co-expressed in chemosensory neurons, our data suggest Ir76b and Ir25a also work in tandem in other insects.

Ionotropic receptors mediate nitrogenous waste avoidance in Drosophila melanogaster

Ammonia and its amine-containing derivatives are widely found in natural decomposition byproducts. Here, we conducted biased chemoreceptor screening to investigate the mechanisms by which different concentrations of ammonium salt, urea, and putrescine in rotten fruits affect feeding and oviposition behavior. We identified three ionotropic receptors, including the two broadly required IR25a and IR76b receptors, as well as the narrowly tuned IR51b receptor. These three IRs were fundamental in eliciting avoidance against nitrogenous waste products, which is mediated by bitter-sensing gustatory receptor neurons (GRNs). The aversion of nitrogenous wastes was evaluated by the cellular requirement by expressing Kir2.1 and behavioral recoveries of the mutants in bitter-sensing GRNs. Furthermore, by conducting electrophysiology assays, we confirmed that ammonia compounds are aversive in taste as they directly activated bitter-sensing GRNs. Therefore, our findings provide insights into the ecological roles of IRs as a means to detect and avoid toxic nitrogenous waste products in nature.

Lineage, Identity, and Fate of Distinct Progenitor Populations in the Embryonic Olfactory Epithelium

We defined a temporal dimension of precursor diversity and lineage in the developing mouse olfactory epithelium (OE) at mid-gestation that results in genesis of distinct cell classes. Slow, symmetrically dividing Meis1+/ Pax7+ progenitors in the early differentiating lateral OE give rise to small numbers of Ascl1+ precursors in the dorsolateral and ventromedial OE. Few of the initial progeny of the Ascl1+ precursors immediately generate olfactory receptor neurons (ORNs). Instead, most early progeny of this temporally defined precursor cohort, labeled via temporally discreet tamoxifen-dependent Ascl1Cre-driven recombination, populate a dorsomedial OE domain comprised of proliferative Ascl1+ as well as Ascl1- cells from which newly generated ORNs are mostly excluded. The most prominent early progeny of these Ascl1+ OE precursors are migratory mass cells associated with the nascent olfactory nerve (ON) in the frontonasal mesenchyme. These temporal, regional and lineage distinctions are matched by differences in proliferative capacity and modes of division in isolated, molecularly distinct lateral versus medial OE precursors. By late gestation, the progeny of the temporally and spatially defined Ascl1+ precursor cohort include few proliferating precursors. Instead, these cells generate a substantial subset of OE sustentacular cells, spatially restricted ORNs, and ensheathing cells associated with actively growing as well as mature ON axons. Accordingly, from the earliest stages of OE differentiation, distinct temporal and spatial precursor identities provide a template for acquisition of subsequent OE and ON cellular diversity.

Modeling of human reaction selection following the arrival of an event in the brain

This work proposes a mathematical model about how a reaction is created in the human brain in responseto a particular incoming Information/Event using quantum mechanics and more precisely path integrals theory.The set of action potentials created in a particular neuron N2 is a result of temporal and spatial summationof the signals coming from different neighboring neurons Nx with different dendrite-paths. Each dendritepathof N2 is assumed to be determined by its respective synapse with its neurotransmitters and therefore tohave its particular action S due to its respective neurotransmitters types (excitatory or inhibitory) and etc. Anexternal incoming signal information being initially modulated by recepetor neurons (in eyes, ears...) travelsthrough the neighboring neurons that are linked to the excited receptor neurons. A potential reaction responsesare subsequently created thanks to a final deformed signal in the motor neurons by all the correlated neuralpaths. The total deformation at each neuron is created by different incoming dendrite-paths and their structures(inhibitory or excitatory neurotransmitters and their type), and of course the existence or not of the signal andits frequency coming from each path. Using path Integrals theory, we compute the probability of existence ofthe signal-Information or the potential reaction to the incoming information at each neuron. In this paper wecompute how much the signal-Information has been distorted between two neighboring linked neural pointsincluding if it arrives or not to the neigboring neurons. We propose an Information entropy similar to Shannonone and we demonstrate that this entropy is equivalent to timespace curvature in the Brain.

JIP3 regulates bi-directional organelle transport in neurons through its interaction with dynein and kinesin-1

The conserved MAP kinase and motor scaffold JIP3 prevents excess lysosome accumulation in axons of vertebrates and invertebrates. Whether and how JIP3's interaction with dynein and kinesin-1 contributes to this critical organelle clearance function is unclear. Using purified recombinant human proteins, we show that dynein light intermediate chain (DLIC) binds to the N-terminal RH1 domain of JIP3, its paralog JIP4, and the lysosomal adaptor RILP. A point mutation in a hydrophobic pocket of the RH1 domain, previously shown to abrogate RILPL2 binding to myosin Va, abrogates the binding of JIP3/4 and RILP to DLIC without perturbing the interaction between the JIP3 RH1 domain and kinesin heavy chain. Characterization of this separation-of-function mutation in Caenorhabditis elegans shows that JIP3-bound dynein is required for organelle clearance in the anterior process of touch receptor neurons. Unlike JIP3 null mutants, JIP3 that cannot bind DLIC causes prominent accumulation of endo-lysosomal organelles at the neurite tip, which is rescued by a disease-associated point mutation in JIP3's leucine zipper that abrogates kinesin light chain binding. These results highlight that RH1 domains are interaction hubs for cytoskeletal motors and suggest that JIP3-bound dynein and kinesin-1 participate in bi-directional organelle transport.

Geosmin suppresses defensive behaviour and elicits unusual neural responses in honey bees.

Geosmin is an odorant produced by bacteria in moist soil. It has been found to be extraordinarily relevant to some insects, but the reasons for this are not yet fully understood. Here we report the first tests of the effect of geosmin on honey bees. A stinging assay showed that the defensive behaviour elicited by the bee's alarm pheromone is strongly suppressed by geosmin. Surprisingly, the suppression is, however, only present at very low geosmin concentrations, and completely disappears at higher concentrations. We investigated the underlying mechanisms of the behavioural change at the level of the olfactory receptor neurons by means of electroantennography and at the level of the antennal lobe output via calcium imaging. Unusual effects were observed at both levels. The responses of the olfactory receptor neurons to mixtures of geosmin and the alarm pheromone component isoamyl acetate (IAA) were lower than to pure IAA, suggesting an interaction of both compounds at the olfactory receptor level. In the antennal lobe, the neuronal representation of geosmin showed a glomerular activation that decreased with increasing concentration, correlating well with the concentration dependence of the behaviour. Computational modelling of odour transduction and odour coding in the antennal lobe suggests that a broader than usual activation of different olfactory receptor types by geosmin in combination with lateral inhibition in the antennal lobe could lead to the observed non-monotonic increasing-decreasing responses to geosmin and thus underlie the specificity of the behavioural response to low geosmin concentrations.

Distinct interhemispheric connectivity at the level of the olfactory bulb emerges during Xenopus laevis metamorphosis

During metamorphosis, the olfactory system of anuran tadpoles undergoes substantial restructuring. The main olfactory epithelium in the principal nasal cavity of Xenopus laevis tadpoles is associated with aquatic olfaction and transformed into the adult air-nose, while a new adult water-nose emerges in the middle cavity. Impacts of this metamorphic remodeling on odor processing, behavior, and network structure are still unexplored. Here, we used neuronal tracings, calcium imaging, and behavioral experiments to examine the functional connectivity between the epithelium and the main olfactory bulb during metamorphosis. In tadpoles, olfactory receptor neurons in the principal cavity project axons to glomeruli in the ventral main olfactory bulb. These projections are gradually replaced by receptor neuron axons from the newly forming middle cavity epithelium. Despite this reorganization in the ventral bulb, two spatially segregated odor processing streams remain undisrupted and behavioral responses to waterborne odorants are unchanged. Contemporaneously, new receptor neurons in the remodeling principal cavity innervate the emerging dorsal part of the bulb, which displays distinct wiring features. Glomeruli around its midline are innervated from the left and right nasal epithelia. Additionally, postsynaptic projection neurons in the dorsal bulb predominantly connect to multiple glomeruli, while half of projection neurons in the ventral bulb are uni-glomerular. Our results show that the “water system” remains functional despite metamorphic reconstruction. The network differences between the dorsal and ventral olfactory bulb imply a higher degree of odor integration in the dorsal main olfactory bulb. This is possibly connected with the processing of different odorants, airborne vs. waterborne.

Natural variation at the Drosophila melanogaster Or22 odorant receptor locus is associated with changes in olfactory behaviour

In insects, many critical olfactory behaviours are mediated by the large odorant receptor ( Or ) gene family, which determines the response properties of different classes of olfactory receptor neurons (ORNs). While ORN responses are generally conserved within and between Drosophila species, variant alleles of the D. melanogaster Or22 locus have previously been shown to alter the response profile of an ORN class called ab3A. These alleles show potential clinal variation, suggesting that selection is acting at this locus. Here, we investigated if the changes seen in ab3A responses lead to changes in olfactory-related behaviours. We show that variation at the Or22 locus and in the ab3A neurons are not fully compensated for by other ORNs and lead to overall changes in antennal odorant detection. We further show that this correlates with differences in odorant preference behaviour and with differences in oviposition site preference, with flies that have the chimaeric short allele strongly preferring to oviposit on banana. These findings indicate that variation at the Or22 locus leads to changes in olfactory-driven behaviours, and add support to the idea that the ab3A neurons are of especial importance to the ecology of Drosophila flies.