Short-term memory and olfactory signal processing

Modern neural recording methodologies, including multi-electrode and optical recordings, allow us to monitor the large population of neurons with high temporal resolution. Such recordings provide rich datasets that are expected to understand better how information about the external world is internally represented and how these representations are altered over time. Achieving this goal requires the development of novel pattern recognition methods and/or the application of existing statistical methods in novel ways to gain insights into basic neural computational principles. In this dissertation, I will take this data-driven approach to dissect the role of short-term memory in olfactory signal processing in two relatively simple models of the olfactory system: fruit fly (Drosophila melanogaster) and locust (Schistocerca americana). First, I will focus on understanding how odor representations within a single stimulus exposure are refined across different populations of neurons (faster dynamics; on the order seconds) in the early olfactory circuits. Using light-sheet imaging datasets from transgenic flies expressing calcium indicators in select populations of neurons, I will reveal how odor representations are decorrelated over time in different neural populations. Further, I will examine how this computation is altered by short-term memory in this neural circuitry. Next, I will examine how neural representations for odorants at an ensemble level are altered across different exposures (slower dynamics; on the order of tens of seconds to minutes). I will examine the role of this short-term adaptation in altering neural representations for odor identity and intensity. Lastly, I will present approaches to help achieve robustness against both extrinsic and intrinsic perturbations of odor-evoked neural responses. I will conclude with a Boolean neural network inspired by the insect olfactory system and compare its performance against other state-of-the-art methods on standard machine learning benchmark datasets. In sum, this work will provide deeper insights into how short-term plasticity alters sensory neural representations and their computational significance

Evolution and structural analysis of Glossina morsitans (Diptera; Glossinidae) Tetraspanins

Tetraspanins are important conserved integral membrane proteins expressed in many organisms. Although there is limited knowledge about the full repertoire, evolution and structural characteristics of individual members in various organisms, data obtained so far show that tetraspanins play major roles in membrane biology, visual processing, memory, olfactory signal processing, and mechanosensory antennal inputs. Thus, these proteins are potential targets for control of insect pests. Here, we report that the genome of the tsetse fly, Glossina morsitans (Diptera: Glossinidae) encodes at least seventeen tetraspanins (GmTsps), all containing the signature features found in the tetraspanin superfamily members. Whereas six of the GmTsps have been previously reported, eleven could be classified as novel because their amino acid sequences do not map to characterized tetraspanins in the available protein data bases. We present a model of the GmTsps by using GmTsp42Ed, whose presence and expression has been recently detected by transcriptomics and proteomics analyses of G. morsitans. Phylogenetically, the identified GmTsps segregate into three major clusters. Structurally, the GmTsps are largely similar to vertebrate tetraspanins. In view of the exploitation of tetraspanins by organisms for survival, these proteins could be targeted using specific antibodies, recombinant large extracellular loop (LEL) domains, small-molecule mimetics and siRNAs as potential novel and efficacious putative targets to combat African trypanosomiasis by killing the tsetse fly vector

Relating Neural Dynamics to Olfactory Coding and Behavior

Sensory stimuli often evoke temporal patterns of spiking activity across a population of neurons in the early processing stages. What features of these spatiotemporal responses encode behaviorally relevant information, and how dynamic processing of sensory signals facilitates information processing are fundamental problems in sensory neuroscience that remain to be understood. In this thesis, I have investigated these issues using a relatively simple invertebrate model (locusts; Schistocerca americana). In locusts, odorants are transduced into electrical signals by olfactory sensory neurons in the antenna and are subsequently relayed to the downstream neural circuit in the antennal lobe (analogous to the olfactory bulb in vertebrates). We found that the sensory input evoked by an odorant could vary depending on whether the stimulus was presented solitarily or in an overlapping sequence following another cue. These inconsistent sensory inputs triggered dynamic reorganization of ensemble activity in the downstream antennal lobe. As a result, we found that the neural activities evoked by an odorant pattern-matched across conditions, thereby providing a basis for invariant stimulus recognition. Notably, we found that only the combination of neurons activated by an odorant was conserved across conditions. The temporal structure of the ensemble neural responses, on the other hand, varied depending on stimulus history: synchronous ensemble firings when stimulated by a novel odorant compared to asynchronous activities induced by a redundant stimulus. Furthermore, these neural responses were refined on a slower timescale (on the order of minutes, i.e. happening over trials) such that the same information about odorant identity and intensity was represented with fewer spikes. We validated these interpretations of our physiological data using results from multiple quantitative behavioral assays. In sum, this thesis work provides fundamental insights regarding behaviorally important features of olfactory signal processing in a relatively simple biological olfactory system

, nevertheless,

Derived from transitions, my artistic practice is an act of condolence for the transient presence that takes time and indulges every process as an acceptance of loss. Over the years, I have moved between distinctive regions and cultures, only to be disoriented by mementos that are residues of a seemingly in- accessible past. What remains is to witness the vanished moments that evoke associated memories. I tend to solidify the volatile condition of transition by carving a temporary fragment on a permanent surface to make the ephemeral, eternal. The attempt to preserve a transitory phenomenon through archives by utilizing digital photography and various mediums inevitably leads to an alteration of memory. The intrinsic presence disappears when it is retained, duplicated, and remembered. Retrospection makes memories fade. The process of recall supplants experience with imagery, often tied to a photo or another cue, that displaces the initial experience. I understand memory to be an ephemeral transition constructed and reconstructed through one’s sensory perception. Accepting that transitions are inevitable, I released my eagerness to grasp every reminiscence of the bygone past. Through the properties of olfaction, which is persistent in the form of memory but cannot be stored or duplicated, I articulate and reconstruct ephemeral autobiographical memories through scent. I focus on insignificant transitions, which are often taken for granted, unnoticed, and forgotten. Between those transitions, I am engaged in meticulously dissecting the exquisite fragments of each moment. My practice is a personal memoir that ultimately characterizes specific correlations between various autobiographical retrieval cues and the level of modification to memories. Operating under the premise that odor-evoked memories are persistent, I use the characteristics of scented material in association with visual cues to determine the level of alteration in memories

Dengue virus infection changes Aedes aegypti oviposition olfactory preferences

Aedes aegypti mosquitoes, main vectors for numerous flaviviruses, have olfactory preferences and are capable of olfactory learning especially when seeking their required environmental conditions to lay their eggs. In this study, we showed that semiochemical conditions during Aedes aegypti larval rearing affected future female choice for oviposition: water-reared mosquitoes preferred to lay eggs in water or p-cresol containers, while skatole reared mosquitoes preferred skatole sites. Using two independent behavioural assays, we showed that this skatole preference was lost in mosquitoes infected with dengue virus. Viral RNA was extracted from infected female mosquito heads, and an increase of virus load was detected from 3 to 10 days post infection, indicating replication in the insect head and possibly in the central nervous system. Expression of selected genes, potentially implied in olfactory learning processes, were also altered during dengue infection. Based on these results, we hypothesise that dengue virus infection alters gene expression in the mosquito\u27s head and is associated with a loss of olfactory preferences, possibly modifying oviposition site choice of female mosquitoes

Odor-Induced Neuronal Rhythms in the Olfactory Bulb Are Profoundly Modified in ob/ob Obese Mice

Leptin, the product of the Ob(Lep) gene, is a peptide hormone that plays a major role in maintaining the balance between food intake and energy expenditure. In the brain, leptin receptors are expressed by hypothalamic cells but also in the olfactory bulb, the first central structure coding for odors, suggesting a precise function of this hormone in odor-evoked activities. Although olfaction plays a key role in feeding behavior, the ability of the olfactory bulb to integrate the energy-related signal leptin is still missing. Therefore, we studied the fate of odor-induced activity in the olfactory bulb in the genetic context of leptin deficiency using the obese ob/ob mice. By means of an odor discrimination task with concomitant local field potential recordings, we showed that ob/ob mice perform better than wild-type (WT) mice in the early stage of the task. This behavioral gain of function was associated in parallel with profound changes in neuronal oscillations in the olfactory bulb. The distribution of the peaks in the gamma frequency range was shifted toward higher frequencies in ob/ob mice compared to WT mice before learning. More notably, beta oscillatory activity, which has been shown previously to be correlated with olfactory discrimination learning, was longer and stronger in expert ob/ob mice after learning. Since oscillations in the olfactory bulb emerge from mitral to granule cell interactions, our results suggest that cellular dynamics in the olfactory bulb are deeply modified in ob/ob mice in the context of olfactory learning

GABAergic Projection Neurons Route Selective Olfactory Inputs to Specific Higher-Order Neurons

SummaryWe characterize an inhibitory circuit motif in the Drosophila olfactory system, parallel inhibition, which differs from feedforward or feedback inhibition. Excitatory and GABAergic inhibitory projection neurons (ePNs and iPNs) each receive input from antennal lobe glomeruli and send parallel output to the lateral horn, a higher center implicated in regulating innate olfactory behavior. Ca2+ imaging of specific lateral horn neurons as an olfactory readout revealed that iPNs selectively suppressed food-related odor responses, but spared signal transmission from pheromone channels. Coapplying food odorant did not affect pheromone signal transmission, suggesting that the differential effects likely result from connection specificity of iPNs, rather than a generalized inhibitory tone. Ca2+ responses in the ePN axon terminals show no detectable suppression by iPNs, arguing against presynaptic inhibition as a primary mechanism. The parallel inhibition motif may provide specificity in inhibition to funnel specific olfactory information, such as food and pheromone, into distinct downstream circuits

General Chemical Reaction Network Theory for Olfactory Sensing Based on G-Protein-Coupled Receptors : Elucidation of Odorant Mixture Effects and Agonist-Synergist Threshold

This work presents a general chemical reaction network theory for olfactory sensing processes that employ G-protein-coupled receptors as olfactory receptors (ORs). The theory is applicable to general mixtures of odorants and an arbitrary number of ORs. Reactions of ORs with G-proteins, both in the presence and the absence of odorants, are explicitly considered. A unique feature of the theory is the definition of an odor activity vector consisting of strengths of odorant-induced signals from ORs relative to those due to background G-protein activity in the absence of odorants. It is demonstrated that each component of the odor activity defined this way reduces to a Michaelis-Menten form capable of accounting for cooperation or competition effects between different odorants. The main features of the theory are illustrated for a two-odorant mixture. Known and potential mixture effects, such as suppression, shadowing, inhibition, and synergy are quantitatively described. Effects of relative values of rate constants, basal activity, and G-protein concentration are also demonstrated