Auswahl der wissenschaftlichen Literatur zum Thema „Olfactory circuit“

Drosophila is a simple and genetically tractable model system for studying neural circuits. This dissertation consists of two studies, with the broad goal of understanding sensory processing in neural circuits using Drosophila as a model system.

Les cellules periglomerulaires du bulbe olfactif conforment une population hétérogène avec des propriétés moléculaires, synaptiques, morphologiques et biophysiques diverses toujours étudiés de façon indépendante. Toutefois, cette diversité suggère que des groupes différents des cellules periglomerulaires pourraient avoir des rôles différents. Dans la première partie de ma thèse je cherche à associer, pour la première fois, différents marqueurs de la diversité des neurones periglomerulaires de façon à aider à comprendre les potentielles implications fonctionnelles que les cellules periglomerulaires pourraient avoir dans le traitement de l’information olfactive. Les cellules periglomerulaires reçoivent des courants inhibiteurs postsynaptiques mais les circuits responsables de cette inhibition restent méconnus. À l’aide des enregistrements électrophysiologiques dans des tranches aiguës horizontales de bulbe olfactif de souris et des techniques d’optogénétique je montre que des projections centrifuges GABAergiques en provenance du télencéphale basal modulent fortement l’inhibition des cellules periglomerulaires de type 2 ainsi que des cellules granulaires et des cellules à axone courtes<br>In the olfactory bulb periglomerular cells form a heterogeneous population with diverse molecular, synaptic, morphological and biophysical properties that have always been considered independently and never explored together. However, such diversity suggests different functional implications. On the first part of this thesis, I aim to associate, for the first time, different markers of periglomerular diversity together to put in perspective the functional implications that differebt subgroups of these cells could exert in odor processing. Periglomerular cells receive inhibitory postsynaptic currents but the circuits mediating this inhibition remain poorly understood. Using a combination of patch-clamp recordings in mouse horizontal olfactory bulb slices and optogenetics I demonstrate that centrifugal GABAergic projections from the basal forebrain strongly mediate inhibition of type 2 periglomerular cells but also granule cells and deep short axon cells

For all animals it is highly advantageous to associate an environmental sensory stimulus with a reinforcing experience. During associative learning, the neural representation of the sensory stimulus (conditioned stimulus; CS) converges in time and location with that of the reinforcer (unconditioned stimulus; US). The CS is then affiliated with a predictive value, altering the animal’s response towards it in following exposures. In my PhD thesis I made use of olfactory aversive conditioning in Drosophila to ask where these two different stimuli are represented and how they are processed in the nervous system to allow association. In the first part of my thesis, I investigated the presentation of the odor stimulus (CS) and its underlying neuronal pathway. CS-US association is possible even when the US is presented after the physical sensory stimulus is gone ('trace conditioning'). I compared such association of temporally non-overlapping stimuli to learning of overlapping stimuli ('delay conditioning'). I found that flies associate an odor trace with electric shock reinforcement even when they were separated with a 15 s gap. Memories after trace and delay conditioning have striking similarities: both reached the same asymptotic learning level, although at different rates, and both memories have similar decay kinetics and highly correlated generalization profiles across odors. Altogether, these results point at a common odor percept which is probably kept in the nervous system throughout and following odor presentation. In search of the physiological correlate of the odor trace, we used in vivo calcium imaging to characterize the odor-evoked activity of the olfactory receptor neurons (ORNs) in the antennal lobe (in collaboration with Alja Luedke, Konstanz University). After the offset of odor presentation, ORNs showed odor-specific response patterns that lasted for a few seconds and were fundamentally different from the response patterns during odor stimulation. Weak correlation between the behavioral odor generalization profile in trace conditioning and the physiological odor similarity profiles in the antennal lobe suggest that the odor trace used for associative learning may be encoded downstream of the ORNs. In the second part of the thesis I investigated the presentation of different aversive stimuli (USs) and their underlying neuronal pathways. I established an odor-temperature conditioning assay, comparable to the commonly used odor-shock conditioning, and compared the neural pathways mediating both memory types. I described a specific sensory pathway for increased temperature as an aversive reinforcement: the thermal sensors AC neurons, expressing dTrpA1 receptors. Despite the separate sensory pathways for odor-temperature and odor-shock conditioning, both converge to one central pathway: the dopamine neurons, generally signaling reinforcement in the fly brain. Although a common population of dopamine neurons mediates both reinforcement types, the population mediating temperature reinforcement is smaller, and probably included within the population of dopamine neurons mediating shock reinforcement. I conclude that dopamine neurons integrate different noxious signals into a general aversive reinforcement pathway. Altogether, my results contribute to our understanding of aversive olfactory conditioning, demonstrating previously undescribed behavioral abilities of flies and their neuronal representations.

The mammalian olfactory system is strikingly shallow. While peripheral input in other sensory systems is sequentially processed by brainstem, midbrain, and thalamic nuclei before reaching primary sensory and associational cortices, olfactory input is processed by only a single region of the brain – the main olfactory bulb – before reaching higher cortical areas. A tremendous amount of neural processing is thus compressed within the main olfactory bulb, making this region of the brain uniquely well suited for investigating fundamental principles of neural processing. Currently, the identity and functional roles of multiple cell types and circuits within the main olfactory bulb remain almost entirely unknown, significantly limiting our understanding of olfaction. Herein, I describe a set of studies addressing this broad gap in knowledge. In Chapter 1, I introduce the known cellular and circuit components of the main olfactory bulb. In Chapter 2, I examine the complexity in biophysical cell-to-cell differences among mitral cells, a class of principal neurons in the main olfactory bulb, and quantify how this within-class diversity regulates mitral cell synchrony. In Chapter 3, I systematically explore synaptic and intrinsic biophysical properties to functionally establish mitral cells and tufted cells as two distinct classes of principal neurons in the main olfactory bulb. In Chapter 4, I reveal that disinhibitory circuitry mediated by a largely uncharacterized class of interneurons is widespread throughout the main olfactory bulb and critically involved in regulating the sensory-evoked activity of inhibitory granule cells. In Chapter 4 Appendix, I provide the first quantitative evidence for the morphological and functional subdivision of granule cells into two distinct classes that separately interact with mitral cells and tufted cells. In Chapter 5 and Chapter 5 Appendix, I molecularly identify a novel class of deep short-axon cells and show that this class of interneurons integrates centrifugal cholinergic input with broadly tuned sensory input and provides highly divergent synaptic output to dynamically regulate the balance of activity between mitral cells and tufted cells. Finally, in Chapters 6 and 7, I present general conclusions from these studies and provide a reappraisal of inhibitory circuitry within the main olfactory bulb.