Olfactory Receptor Neuron Input Research Articles

Short-Term Plasticity Regulates Both Divisive Normalization and Adaptive Responses in Drosophila Olfactory System.

In Drosophila, olfactory information received by olfactory receptor neurons (ORNs) is first processed by an incoherent feed forward neural circuit in the antennal lobe (AL) that consists of ORNs (input), inhibitory local neurons (LNs), and projection neurons (PNs). This “early” olfactory information processing has two important characteristics. First, response of a PN to its cognate ORN is normalized by the overall activity of other ORNs, a phenomenon termed “divisive normalization.” Second, PNs respond strongly to the onset of ORN activities, but they adapt to prolonged or continuously varying inputs. Despite the importance of these characteristics for learning and memory, their underlying mechanisms are not fully understood. Here, we develop a circuit model for describing the ORN-LN-PN dynamics by including key neuron-neuron interactions such as short-term plasticity (STP) and presynaptic inhibition (PI). By fitting our model to experimental data quantitatively, we show that a strong STP balanced between short-term facilitation (STF) and short-term depression (STD) is responsible for the observed nonlinear divisive normalization in Drosophila. Our circuit model suggests that either STP or PI alone can lead to adaptive response. However, by comparing our model results with experimental data, we find that both STP and PI work together to achieve a strong and robust adaptive response. Our model not only helps reveal the mechanisms underlying two main characteristics of the early olfactory process, it can also be used to predict PN responses to arbitrary time-dependent signals and to infer microscopic properties of the circuit (such as the strengths of STF and STD) from the measured input-output relation. Our circuit model may be useful for understanding the role of STP in other sensory systems.

Differences in olfactory bulb mitral cell spiking with ortho- and retronasal stimulation revealed by data-driven models.

The majority of olfaction studies focus on orthonasal stimulation where odors enter via the front nasal cavity, while retronasal olfaction, where odors enter the rear of the nasal cavity during feeding, is understudied. The coding of retronasal odors via coordinated spiking of neurons in the olfactory bulb (OB) is largely unknown despite evidence that higher level processing is different than orthonasal. To this end, we use multi-electrode array in vivo recordings of rat OB mitral cells (MC) in response to a food odor with both modes of stimulation, and find significant differences in evoked firing rates and spike count covariances (i.e., noise correlations). Differences in spiking activity often have implications for sensory coding, thus we develop a single-compartment biophysical OB model that is able to reproduce key properties of important OB cell types. Prior experiments in olfactory receptor neurons (ORN) showed retro stimulation yields slower and spatially smaller ORN inputs than with ortho, yet whether this is consequential for OB activity remains unknown. Indeed with these specifications for ORN inputs, our OB model captures the salient trends in our OB data. We also analyze how first and second order ORN input statistics dynamically transfer to MC spiking statistics with a phenomenological linear-nonlinear filter model, and find that retro inputs result in larger linear filters than ortho inputs. Finally, our models show that the temporal profile of ORN is crucial for capturing our data and is thus a distinguishing feature between ortho and retro stimulation, even at the OB. Using data-driven modeling, we detail how ORN inputs result in differences in OB dynamics and MC spiking statistics. These differences may ultimately shape how ortho and retro odors are coded.

Asymmetric neurotransmitter release enables rapid odour lateralization in Drosophila

In Drosophila, most individual olfactory receptor neurons (ORNs) project bilaterally to both sides of the brain1,2. Having bilateral rather than unilateral projections may represent a useful redundancy. However, bilateral ORN projections to the brain should also compromise the ability to lateralize odors. Nevertheless, walking or flying Drosophila reportedly turn toward their more strongly stimulated antenna3-5. Here we show that each ORN spike releases ~40% more neurotransmitter from the axon branch ipsilateral to the soma, as compared to the contralateral branch. As a result, when an odor activates the antennae asymmetrically, ipsilateral central neurons begin to spike a few milliseconds before contralateral neurons, and ipsilateral central neurons also fire at a 30-50% higher rate. We show that a walking fly can detect a 5% asymmetry in total ORN input to its left and right antennal lobes, and can turn toward the odor in less time than it requires the fly to complete a stride. These results demonstrate that neurotransmitter release properties can be tuned independently at output synapses formed by a single axon onto two target cells with identical functions and morphologies. Our data also show that small differences in spike timing and spike rate can produce reliable differences in olfactory behavior.

Effects of synaptic and intrinsic parameters in shaping dynamic responses to olfactory input: a combined computational-experimental study of two glomerular microcircuits

Initial synaptic processing of odors occurs in the mammalian olfactory bulb (OB): temporally dynamic odorant-evoked inputs are first processed at the olfactory receptor neuron (ORN) level, and similarly dynamic, patterned output is transmitted from the mitral cell (MC) layer to olfactory cortex. Prior work has shown that bursts of odor-evoked ORN activity exhibit odor-specific and glomerulus-specific durations, rise times, latencies, and amplitudes [1]. Similarly diverse patterning is seen in MC activity, which is temporally organized around the respiratory cycle and changes qualitatively during odor sampling. The temporal spread of sensory input following a single inhalation (~100-300 ms) is comparable to the range of discrimination times for different olfactory tasks [2,3], consistent with these dynamics being important in shaping odor perception. Situated between the ORN input and MC output layers, the neuronal circuitry of the glomerular layer acts to consolidate and modulate OB output. Thousands of juxtaglomerular neurons from three distinct classes form the neuronal network within a glomerulus; several synaptic and gap junctional microcircuits have been identified in the intraglomerular network [4]. What transformation(s) of ORN input into MC output might the intraglomerular circuitry perform? We investigate temporal dynamics in computational models of two intraglomerular microcircuits: the classical ORN-MC circuit and a variant circuit that incorporates between the ORN and MC an external tufted (ET) cell capable of endogenous bursting [5]. These neurons are represented with single-compartment, Hodgkin-Huxley-style models [6,7]. Circuit inputs are calcium signals recorded from the presynaptic terminals of ORNs of head-fixed rats exposed to odorants using a ‘sniff playback’ mechanism [8,9]. These calcium signals are converted to excitatory synaptic inputs with temporal signatures closely matching that of inputs to the real neurons. The response dynamics of the circuits’ MC output are strongly shaped by the input signal. We explore how the circuits’ dynamics vary for different odorants, synaptic strengths, and degrees of synaptic adaptation, and we compare the two circuits’ dynamics as parameters controlling intrinsic properties of the ET and MC cells are varied.

Transformation of the Sex Pheromone Signal in the Noctuid Moth Agrotis ipsilon: From Peripheral Input to Antennal Lobe Output

How information is transformed along synaptic processing stages is critically important to understand the neural basis of behavior in any sensory system. In moths, males rely on sex pheromone to find their mating partner. It is essential for a male to recognize the components present in a pheromone blend, their ratio, and the temporal pattern of the signal. To examine pheromone processing mechanisms at different levels of the olfactory pathway, we performed single-cell recordings of olfactory receptor neurons (ORNs) in the antenna and intracellular recordings of central neurons in the macroglomerular complex (MGC) of the antennal lobe of sexually mature Agrotis ipsilon male moths, using the same pheromone stimuli, stimulation protocol, and response analyses. Detailed characteristics of the ORN and MGC-neuron responses were compared to describe the transformation of the neuronal responses that takes place in the MGC. Although the excitatory period of the response is similar in both neuron populations, the addition of an inhibitory phase following the MGC neuron excitatory phase indicates participation of local interneurons (LN), which remodel the ORN input. Moreover, MGC neurons showed a wider tuning and a higher sensitivity to single pheromone components than ORNs.

A combined computational-experimental study of dynamic responses to olfactory input in a glomerular circuit

Odorant-evoked input to and output from the mammalian olfactory bulb (OB) is temporally dynamic. Olfactory receptor neuron (ORN) inputs are tightly coupled to the respiratory cycle, and inhalation-evoked input bursts occur with durations, rise times, latencies, and strengths (amplitudes) that vary across glomeruli (for the same odorant) and also in individual glomeruli for different odorants [1]. The temporal spread of sensory input following a single inhalation (~100-300 ms) is comparable to the range of discrimination times for different olfactory tasks [2,3], consistent with these dynamics being important in shaping odor perception. Similarly diverse temporal patterns of activity occur at the level of output from the OB, among mitral cells (MCs), whose firing patterns express strong temporal structure organized around the respiratory cycle and modulated by odorant presentation; significant odor information is carried in these temporal patterns across the MC population. We investigate these temporal dynamics using a computational model of the ORN-MC circuit that uses a single-compartment, Hodgkin-Huxley-style MC model [4]. The input to the model MC is taken from recordings of odorant-evoked calcium influx into the presynaptic terminals of ORNs of awake, head-fixed rats engaged in an olfactory discrimination task [1,5]. This calcium signal is converted to an excitatory synaptic input for the model MC having a temporal signature that presumably closely reproduces that of the signal received by real MCs. The response dynamics of the MC model are strongly shaped by the input signal (Figure ​(Figure1).1). We explore how these dynamics vary for different odorants, synaptic strengths, and intrinsic MC parameters. We also investigate the response of a variant circuit that incorporates a mediating external tufted cell model between the ORN and MC [6]. Figure 1 Sniffing and odor-evoked ORN input (top) imaged from an awake rat; ORN input is used to drive a model MC (bottom). Each sniff-evoked burst of ORN input elicits a burst of action potentials in the model MC.

Mechanisms of maximum information preservation in the Drosophila antennal lobe.

We examined the presence of maximum information preservation, which may be a fundamental principle of information transmission in all sensory modalities, in the Drosophila antennal lobe using an experimentally grounded network model and physiological data. Recent studies have shown a nonlinear firing rate transformation between olfactory receptor neurons (ORNs) and second-order projection neurons (PNs). As a result, PNs can use their dynamic range more uniformly than ORNs in response to a diverse set of odors. Although this firing rate transformation is thought to assist the decoder in discriminating between odors, there are no comprehensive, quantitatively supported studies examining this notion. Therefore, we quantitatively investigated the efficiency of this firing rate transformation from the viewpoint of information preservation by computing the mutual information between odor stimuli and PN responses in our network model. In the Drosophila olfactory system, all ORNs and PNs are divided into unique functional processing units called glomeruli. The nonlinear transformation between ORNs and PNs is formed by intraglomerular transformation and interglomerular interaction through local neurons (LNs). By exploring possible nonlinear transformations produced by these two factors in our network model, we found that mutual information is maximized when a weak ORN input is preferentially amplified within a glomerulus and the net LN input to each glomerulus is inhibitory. It is noteworthy that this is the very combination observed experimentally. Furthermore, the shape of the resultant nonlinear transformation is similar to that observed experimentally. These results imply that information related to odor stimuli is almost maximally preserved in the Drosophila olfactory circuit. We also discuss how intraglomerular transformation and interglomerular inhibition combine to maximize mutual information.

A large-scale model of the locust antennal lobe

The antennal lobe (AL) is the primary structure within the locust's brain that receives information from olfactory receptor neurons (ORNs) within the antennae. Different odors activate distinct subsets of ORNs, implying that neuronal signals at the level of the antennae encode odors combinatorially. Within the AL, however, different odors produce signals with long-lasting dynamic transients carried by overlapping neural ensembles, suggesting a more complex coding scheme. In this work we use a large-scale point neuron model of the locust AL to investigate this shift in stimulus encoding and potential consequences for odor discrimination. Consistent with experiment, our model produces stimulus-sensitive, dynamically evolving populations of active AL neurons. Our model relies critically on the persistence time-scale associated with ORN input to the AL, sparse connectivity among projection neurons, and a synaptic slow inhibitory mechanism. Collectively, these architectural features can generate network odor representations of considerably higher dimension than would be generated by a direct feed-forward representation of stimulus space.

A neuronal network model for the detection of binary odor mixtures

Event Abstract Back to Event A neuronal network model for the detection of binary odor mixtures In many lepidopteran species, males are attracted to females by pheromones, which typically are specific blends of two or more components. We constructed a minimal model, consistent with the known electrophysiology and structure of the Macroglomerular Complex (the site of odor processing specific to the male antennal lobe), that selectively responds to a blend of pheromone components in a fixed ratio over a wide range of concentrations. In the model the olfactory receptor neurons (ORNs) are represented by two groups of 200 Poisson neurons, each group responding specifically to one pheromone component. The concentration of the sensed component is encoded as the firing rate of the Poisson neurons. The ORN populations project to three groups of primary local neurons (LNs). These inhibit both each other and two intrinsically active secondary LNs, which in turn inhibit an intrinsically active projection neuron (PN). The underlying principle is the competition of the three primary LNs: given appropriate component concentrations and inter-LN synaptic strengths, the generalist LN becomes active and suppresses the two specialist LNs, both secondary LNs are inhibited and the PN is disinhibited to signal the presence of the correct blend. All LNs and the PN are implemented as Hodgkin-Huxley neurons. We tested the model with stimuli including all combinations of component concentrations, where the frequency of ORNs was in the range of 10 to 100 Hz in 10 Hz increments. Calculating the spike density function for the PN at midpoint of each stimulus presentation, we obtained a 10×10 response matrix for all combinations. An optimal response corresponds to a matrix with maximal values on the diagonal and 0 off-diagonal. We designed a 'success functional' by convolution of the response matrix with such a target response profile and, to optimize it, adjusted the synaptic strength on the following connections: ORNs to primary specialist LNs, ORNs to primary generalist LNs, and on all interconnections between primary LNs. We observed that (a) the relative strength of inputs from ORNs to specialist and generalist primary LNs must be specific (55-65% specialist compared to generalist strength for 1:1 pheromone ratio); (b) similarly, generalist-specialist, specialist-generalist and inter-specialist connections must have balanced synaptic strengths (in a ratio close to 0.94:1.20:1.10 for 1:1 component ratio). Modulation of ORN-LN connections ensures proper ?engagement? of the generalist LN, while LN interconnections appear essential in narrowing the generalist LN response, failing which the responses lose specificity to the component ratio. Finally, the number of ORNs needs to be large enough (hundreds) to avoid instances of 'false starts', where the generalist LNs starts spiking at the onset of a stimulus with an inappropriate pheromone component ratio simply due to the irregularity of ORN input. A further improvement is achieved by using LN groups (of 3 in this model) instead of individual LNs. This work was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/F005113/1). Conference: Computational and systems neuroscience 2009, Salt Lake City, UT, United States, 26 Feb - 3 Mar, 2009. Presentation Type: Poster Presentation Topic: Poster Presentations Citation: (2009). A neuronal network model for the detection of binary odor mixtures. Front. Syst. Neurosci. Conference Abstract: Computational and systems neuroscience 2009. doi: 10.3389/conf.neuro.06.2009.03.236 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Feb 2009; Published Online: 03 Feb 2009. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract Supplemental Data The Authors in Frontiers Google Google Scholar PubMed Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Temporal Structure of Receptor Neuron Input to the Olfactory Bulb Imaged in Behaving Rats

The dynamics of sensory input to the nervous system play a critical role in shaping higher-level processing. In the olfactory system, the dynamics of input from olfactory receptor neurons (ORNs) are poorly characterized and depend on multiple factors, including respiration-driven airflow through the nasal cavity, odorant sorption kinetics, receptor-ligand interactions between odorant and receptor, and the electrophysiological properties of ORNs. Here, we provide a detailed characterization of the temporal organization of ORN input to the mammalian olfactory bulb (OB) during natural respiration, using calcium imaging to monitor ORN input to the OB in awake, head-fixed rats expressing odor-guided behaviors. We report several key findings. First, across a population of homotypic ORNs, each inhalation of odorant evokes a burst of action potentials having a rise time of about 80 ms and a duration of about 100 ms. This rise time indicates a relatively slow, progressive increase in ORN activation as odorant flows through the nasal cavity. Second, the dynamics of ORN input differ among glomeruli and for different odorants and concentrations, but remain reliable across successive inhalations. Third, inhalation alone (in the absence of odorant) evokes ORN input to a significant fraction of OB glomeruli. Finally, high-frequency sniffing of odorant strongly reduces the temporal coupling between ORN inputs and the respiratory cycle. These results suggest that the dynamics of sensory input to the olfactory system may play a role in coding odor information and that, in the awake animal, strategies for processing odor information may change as a function of sampling behavior.

Co-Transmission of Dopamine and GABA in Periglomerular Cells

Most central neurons package and release a single transmitter. However co-transmission of fast-acting and modulatory transmitters has been observed in vertebrate and invertebrate systems. Here we describe a population of periglomerular cells in mouse brain slices (PND14-21) that co-release dopamine and GABA. We made whole cell recordings from periglomerular cells that expressed enhanced green fluorescent protein (EGFP) under the control of the tyrosine hyrdoxylase (TH) promoter. Immunolabeling confirmed that EGFP+ periglomerular cells synthesized TH as well as glutamic acid decarboxylase (GAD). Stimulation of olfactory receptor neuron (ORN) afferent input evoked excitatory postsynaptic currents (EPSCs) in EGFP+ cells that were inhibited by cocaine, which blocks dopamine transport. These effects were reversed by the D2 receptor antagonist sulpiride. Cocaine also increased the paired-pulse ratio of ORN-evoked EPSCs. These results demonstrate that TH+ periglomerular cells spontaneously release dopamine. In addition to dopamine, TH-EGFP+ cells also released GABA. Brief depolarizing voltage steps in labeled cells evoked a tail current that was completely blocked by the GABA(A) receptor antagonist gabazine and by cadmium, indicative of calcium-dependent self-inhibition in periglomerular cells. However, similar voltage steps were insufficient to cause D2-receptor mediated inhibition of ORN terminals. Our results indicate that TH+ periglomerular cells are directly activated by ORN input and release both dopamine and GABA. We suggest that concerted activation of multiple periglomerular cells may be required to detect dopamine release under normal physiological conditions.

Propagation of olfactory information in Drosophila

Investigating how information propagates between layers in the olfactory system is an important step toward understanding the olfactory code. Each glomerular output projection neuron (PN) receives two sources of input: the olfactory receptor neurons (ORNs) of the same glomerulus and interneurons that innervate many glomeruli. We therefore asked how these inputs interact to produce PN output. We used receptor gene mutations to silence all of the ORNs innervating a specific glomerulus and recorded PN activity with two-photon calcium imaging and electrophysiology. We found evidence for balanced excitatory and inhibitory synaptic inputs but saw little or no response in the absence of direct ORN input. We next asked whether any transformation of activity occurs at successive layers of the antennal lobe. We found a strong link between PN firing and dendritic calcium elevation, the latter of which is tightly correlated with calcium activity in ORN axons, supporting the idea of glomerular propagation of olfactory information. Finally, we showed that odors are represented by a sparse population of PNs. Together, these results are consistent with the idea that direct receptor input provides the main excitatory drive to PNs, whereas interneurons modulate PN output. Balanced excitatory and inhibitory interneuron input may provide a mechanism to adjust PN sensitivity.

The role of sniffing in shaping the primary receptor code for odors

The basic strategy by which the olfactory system encodes odor information arises from the molecular biology and anatomical projections of olfactory receptor neurons (ORNs). Each ORN expresses a single receptor protein that determines the neuron's sensitivity to particular odorants. All ORNs expressing the same receptor converge onto the same glomerulus in the olfactory bulb (OB), creating a map of receptor and odorant identity on the surface of the OB. However, a critical feature of the olfactory system is that odorant access to ORNs is controlled by the rhythmic inspiration and expiration of air through the nose (‘sniffing’), a process heavily modulated by behavioral state. To address how sniffing shapes primary receptor codes for odors, we have imaged ORN input to the OB in awake rats performing odor discrimination tasks and compared how odors are represented during different sniffing behaviors. We have found that sniffing dramatically alters both temporal and spatial patterns of ORN input to the OB. At low (resting) sniff frequencies, ORNs respond with short bursts of activity following each inhalation and encode information about all odorants present. In contrast, at higher frequencies typical of active investigation, ORNs do not burst after each sniff, show strong and rapid adaptation to continued odor presentation, and primarily encode information about changes in the olfactory environment. Thus, the ‘mode’ of odor coding can be rapidly switched simply by changing sniff frequency. These data show that significant transformations of sensory codes can be controlled by sampling behavior alone. The data also have important implications for how information is processed synaptically in the OB and beyond.

Excitatory Interactions between Olfactory Processing Channels in the Drosophila Antennal Lobe

Each odorant receptor gene defines a unique type of olfactory receptor neuron (ORN) and a corresponding type of second-order neuron. Because each odor can activate multiple ORN types, information must ultimately be integrated across these processing channels to form a unified percept. Here, we show that, in Drosophila, integration begins at the level of second-order projection neurons (PNs). We genetically silence all the ORNs that normally express a particular odorant receptor and find that PNs postsynaptic to the silent glomerulus receive substantial lateral excitatory input from other glomeruli. Genetically confining odor-evoked ORN input to just one glomerulus reveals that most PNs postsynaptic to other glomeruli receive indirect excitatory input from the single ORN type that is active. Lateral connections between identified glomeruli vary in strength, and this pattern of connections is stereotyped across flies. Thus, a dense network of lateral connections distributes odor-evoked excitation between channels in the first brain region of the olfactory processing stream.

Excitatory Local Circuits and Their Implications for Olfactory Processing in the Fly Antennal Lobe

Conflicting views exist of how circuits of the antennal lobe, the insect equivalent of the olfactory bulb, translate input from olfactory receptor neurons (ORNs) into projection-neuron (PN) output. Synaptic connections between ORNs and PNs are one-to-one, yet PNs are more broadly tuned to odors than ORNs. The basis for this difference in receptive range remains unknown. Analyzing a Drosophila mutant lacking ORN input to one glomerulus, we show that some of the apparent complexity in the antennal lobe's output arises from lateral, interglomerular excitation of PNs. We describe a previously unidentified population of cholinergic local neurons (LNs) with multiglomerular processes. These excitatory LNs respond broadly to odors but exhibit little glomerular specificity in their synaptic output, suggesting that PNs are driven by a combination of glomerulus-specific ORN afferents and diffuse LN excitation. Lateral excitation may boost PN signals and enhance their transmission to third-order neurons in a mechanism akin to stochastic resonance.

Odorant Response Properties of Convergent Olfactory Receptor Neurons

Information about odorant stimuli is thought to be represented in spatial and temporal patterns of activity across neurons in the olfactory epithelium and the olfactory bulb (OB). Previous studies suggest that olfactory receptor neurons (ORNs) distributed in the nasal cavity project to localized regions in the glomerular layer of the OB. However, the functional significance of this convergence is not yet known, and in no studies have the odorant response properties of individual ORNs projecting to defined OB regions been measured directly. We have retrogradely labeled mouse ORNs connecting to different glomeruli in the dorsal OB and tested single cells for responses to odorants using fura-2 calcium imaging. ORNs that project to clusters of dorsomedial (DM) glomeruli exhibit different odorant response profiles from those that project to dorsolateral (DL) glomeruli. DL-projecting ORNs showed responses to compounds with widely different structures, including carvone, eugenol, cinnamaldehyde, and acetophenone. In contrast, DM-projecting neurons exhibited responses to a more structurally restricted set of compounds and responded preferentially to organic acids. These data demonstrate that ORN afferents segregate by odorant responsiveness and that the homogeneity of ORN and glomerular input varies with different OB regions. The data also demonstrate that a subpopulation of ORNs projecting to DM glomeruli is functionally similar.