@phdthesis{Saumweber2011,
  author    = {Saumweber, Timo},
  title     = {Mechanism of Learning and Plasticity in Larval Drosophila},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66354},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {According to a changing environment it is crucial for animals to make experience and learn about it. Sensing, integrating and learning to associate different kinds of modalities enables animals to expect future events and to adjust behavior in the way, expected as the most profitable. Complex processes as memory formation and storage make it necessary to investigate learning and memory on different levels. In this context Drosophila melanogaster represents a powerful model organism. As the adult brain of the fly is still quite complex, I chose the third instar larva as model - the more simple the system, the easier to isolate single, fundamental principles of learning. In this thesis I addressed several kinds of questions on different mechanism of olfactory associative and synaptic plasiticity in Drosophila larvae. I focused on short-term memory throughout my thesis. First, investigating larval learning on behavioral level, I developed a one-odor paradigm for olfactory associative conditioning. This enables to estimate the learnability of single odors, reduces the complexity of the task and simplify analyses of "learning mutants". It further allows to balance learnability of odors for generalization-type experiments to describe the olfactory "coding space". Furthermore I could show that innate attractiveness and learnability can be dissociated and found finally that paired presentation of a given odor with reward increase performance, whereas unpaired presentations of these two stimuli decrease performance, indicating that larva are able to learn about the presence as well as about the absence of a reward. Second, on behavioral level, together with Thomas Niewalda and colleagues we focussed on salt processing in the context of choice, feeding and learning. Salt is required in several physiological processes, but can neither be synthesized nor stored. Various salt concentrations shift the valence from attraction to repulsion in reflexive behaviour. Interestingly, the reinforcing effect of salt in learning is shifted by more than one order of magnitude toward higher concentrations. Thus, the input pathways for gustatory behavior appear to be more sensitive than the ones supporting gustatory reinforcement, which is may be due to the dissociation of the reflexive and the reinforcing signalling pathways of salt. Third, in cooperation with Michael Schleyer we performed a series of behavioral gustatory, olfactory preference tests and larval learning experiments. Based on the available neuroanatomical and behavioral data we propose a model regarding chemosensory processing, odor-tastant memory trace formation and the 'decision' like process. It incorporates putative sites of interaction between olfactory and gustatory pathways during the establishment as well as behavioral expression of odor-tastant memory. We claim that innate olfactory behavior is responsive in nature and suggest that associative conditioned behavior is not a simple substitution like process, but driven more likely by the expectation of its outcome. Fourth, together with Birgit Michels and colleagues we investigated the cellular site and molecular mode of Synapsin, an evolutionarily conserved, presynaptic vesicular phosphoprotein and its action in larval learning. We confirmed a previously described learning impairment upon loss of Synapsin. We localized this Synapsin dependent memory trace in the mushroom bodies, a third-order "cortical" brain region, and could further show on molecular level, that Synapsin is as a downstream element of the AC-cAMP-PKA signalling cascade. This study provides a comprehensive chain of explanation from the molecular level to an associative behavioral change. Fifth, in the main part of my thesis I focused on molecular level on another synaptic protein, the Synapse associated protein of 47kDa (Sap47) and its role in larval behavior. As a member of a phylogenetically conserved gene family of hitherto unknown function. It is localized throughout the whole neuropil of larval brains and associated with presynaptic vesicles. Upon loss of Sap47 larvae exhibit normal sensory detection of the to-be-associated stimuli as well as normal motor performance and basic synaptic transmission. Interestingly, short-term plasticity is distorted and odorant-tastant associative learning ability is reduced. This defect in associative function could be rescued by restoring Sap47 expression. Therefore, this report is the first to suggest a function for Sap47 and specifically argues that Sap47 is required for synaptic as well as for behavioral plasticity in Drosophila larva. This prompts the question whether its homologs are required for synaptic and behavioral plasticity also in other species. Further in the last part of my thesis I contributed to the study of Ayse Yarali. Her central topic was the role of the White protein in punishment and relief learning in adult flies. Whereas stimuli that precede shock during training are subsequently avoided as predictors for punishment, stimuli that follow shock during training are later on approached, as they predict relief. Concerning the loss of White we report that pain-relief learning as well as punishment learning is changed. My contribution was a comparison between wild type and the white1118 mutant larvae in odor-reward learning. It turned out that a loss of White has no effect on larval odorant-tastant learning. This study, regarding painrelief learning provides the very first hints concerning the genetic determinants of this form of learning.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Mishra2011,
  author    = {Mishra, Dushyant},
  title     = {The content of olfactory memory in larval Drosophila},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66316},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {An animal depends heavily on its sense of smell and its ability to form olfactory associations as this is crucial for its survival. This thesis studies in two parts about such associative olfactory learning in larval Drosophila. The first part deals with different aspects of odour processing while the second part is concerned with aspects related to memory and learning. Chapter I.1 highlights how odour intensities could be integrated into the olfactory percept of larval Drosophila. I first describe the dose-effect curves of learnability across odour intensities for different odours and then choose odour intensities from these curves such that larvae are trained at intermediate odour intensity, but are tested for retention with either that trained intermediate odour intensity, or with respectively HIGHer or LOWer intensities. I observe a specificity of retention for the trained intensity for all the odours used. Further I compare these findings with the case of adult Drosophila and propose a circuit level model of how such intensity coding comes about. Such intensity specificity of learning adds to appreciate the richness in 'content' of olfactory memory traces, and to define the demands on computational models of olfaction and olfactory learning. Chapter I.2 provides a behaviour-based estimate of odour similarity using four different types of experiments to yield a combined, task-independent estimate of perceived difference between odour-pairs. Further comparison of these perceived differences to published measures of physico- chemical difference reveals a weak correlation. Notable exceptions to this correlation are 3-octanol and benzaldehyde. Chapter I.3 shows for two odours (3-octanol and 1-octene-3-ol) that perceptual differences between these odours can either be ignored after non-discriminative training (generalization), or accentuated by odour-specific reinforcement (discrimination). Anosmic Or83b1 mutants have lost these faculties, indicating that this adaptive adjustment is taking place downstream of Or83b expressing sensory neurons. Chapter II.1 of this thesis deals with food supplementation with dried roots of Rhodiola rosea. This dose-dependently improves odour- reward associative function in larval Drosophila. Supplementing fly food with commercially available tablets or extracts, however, does not have a 'cognitive enhancing' effect, potentially enabling us to differentiate between the effective substances in the root versus these preparations. Thus Drosophila as a genetically tractable study case should now allow accelerated analyses of the molecular mechanism(s) that underlie this 'cognitive enhancement' conveyed by Rhodiola rosea. Chapter II.2 describes the role of Synapsin, an evolutionarily conserved presynaptic phosphoprotein using a combined behavioural and genetic approach and asks where and how, this protein affects functions in associative plasticity of larval Drosophila. This study shows that a Synapsin-dependent memory trace can be pinpointed to the mushroom bodies, a 'cortical' brain region of the insects. On the molecular level, data in this study assign Synapsin as a behaviourally- relevant effector of the AC-cAMP-PKA cascade.},
  subject      = {Drosophila},
  language  = {en}
}
@phdthesis{Langenhan2004,
  author    = {Langenhan, Tobias},
  title     = {Ciliary neurotrophic factor (CNTF) im olfaktorischen System von Ratten und M{\"a}usen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-16009},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2004},
  abstract  = {Das olfaktorische System ist aufgrund seiner lebenslangen regenerativen Kapazit{\"a}t, seines Reichtums an neurotrophen Faktoren und der relativ guten Zug{\"a}nglichkeit f{\"u}r Manipulationen ein attraktiver Gegenstand neurobiologischer Forschung. In der vorliegenden Arbeit wurde die Lokalisation und m{\"o}gliche Funktion des zili{\"a}ren neurotrophen Faktors (CNTF) in der prim{\"a}ren Geruchsbahn mit Hilfe immunhistochemischer Methoden untersucht. Es konnte gezeigt werden, dass die CNTF-Ir bei Ratten und M{\"a}usen in den olfaktorischen Gliazellen (Ensheathingzellen) lokalisiert ist. Elektronenmikroskopische Aufnahmen belegten ein zytoplasmatisches und nukle{\"a}res Vorkommen der CNTF-Ir innerhalb der EC. Ein neues und {\"u}berraschendes Ergebnis der Arbeit ist, dass CNTF in individuellen olfaktorischen Neuronen vorkommt. Bislang wurde CNTF lediglich in Gliazellen des zentralen und peripheren Nervensystems nachgewiesen. Die weitere Charakterisierung der epithelialen CNTF-ir Neurone kennzeichnete diese als reife olfaktorische Nervenzellen. Die CNTF-Ir war mit dem olfaktorischen Markerprotein (OMP) kolokalisiert, einem Marker ausschließlich reifer ON und wies keine Kolokalisation mit dem Growth associated protein 43 (GAP-43) auf, dessen Expression unreife Riechsinneszellen kennzeichnet. CNTF k{\"o}nnte einerseits an lebenslang fortw{\"a}hrenden De- und/oder Regenerationsvorg{\"a}ngen des olfaktorischen Epithels beteiligt sein. Die Exposition der Riechschleimhaut gegen{\"u}ber infekti{\"o}sen, physikalischen und chemischen Noxen bedingt den st{\"a}ndigen Verlust olfaktorischer Neurone und deren lebenslange Regeneration aus neuronalen Vorl{\"a}uferzellen im olfaktorischen Epithel. Die Zellkerne CNTF-ir ON wiesen in der Mehrzahl keine degenerativen Ver{\"a}nderungen wie Kondensierung und Fragmentierung auf, wie es bei gesch{\"a}digten und untergehenden Zellen beobachtet wird. Im olfaktorischen Epithel zeigte sich des weiteren keine neuronale Kolokalisation von CNTF mit der aktivierten Caspase-3, einem Exekutorenzym der Apoptose, wie man es bei apoptotisch degenerierenden Neuronen findet. Nach L{\"a}sionen des olfaktorischen Epithels von M{\"a}usen, die nekrotische Zellunterg{\"a}nge ausl{\"o}sen, konnte kein gesteigertes Vorkommen von CNTF-ir ON gezeigt werden. Eine Einbindung von CNTF in die Mechanismen neuronaler Degeneration erscheint nach den Ergebnissen verschiedener Experimente wenig wahrscheinlich. Eine zweite Erkl{\"a}rung f{\"u}r das individuelle neuronale Auftreten der CNTF-Ir bot die Annahme, dass CNTF mit der Expression olfaktorischer Rezeptorproteine vergesellschaftet sein k{\"o}nnte. Dreidimensionale Rekonstruktionen von Paaren von BO bei Ratten und M{\"a}usen zeigte, dass die Axone CNTF-ir ON in Glomeruli olfactorii projizierten, die bilateralsymmetrisch in beiden BO eines Tieres lokalisiert waren. Diese Symmetrie findet man ebenfalls bei den Projektionen der ON, die das gleiche olfaktorische Rezeptorprotein exprimieren. Die Lokalisation der CNTF-ir innervierten Glomeruli war interindividuell {\"a}hnlich, ihre Anzahl wies jedoch erhebliche Unterschiede auf. Dieses Ph{\"a}nomen l{\"a}sst sich mit Befunden vergleichen, die im Rahmen von olfaktorischen Aktivit{\"a}tsstudien bei M{\"a}usen und Ratten erhoben wurden. Dabei beobachtete man eine Erh{\"o}hung der Anzahl aktivierter Glomeruli mit steigenden Geruchsstoffkonzentrationen. Auffallend war eine deutliche {\"U}bereinstimmung des Verteilungsmusters der CNTF-ir Glomeruli mit dem in der Literatur dargestellten Verteilungsmuster von Glomeruli, die durch Uringer{\"u}che aktiviert werden. Die r{\"a}umliche Rekonstruktion der BO und die Darstellung der Position der CNTF-ir innervierten Glomeruli legt demnach eine neue m{\"o}gliche Funktion von CNTF im olfaktorischen System nah: dessen Einbindung in Ph{\"a}nomene der Aktivit{\"a}t olfaktorischer Nervenzellen und plastischer Prozesse, die an der ersten Synapse der Geruchsbahn stattfinden. In der vorliegenden Arbeit konnte durch die Anwendung von klassischen Methoden der anatomisch-histologischen Forschung die Lokalisation von CNTF in der prim{\"a}ren Geruchsbahn gekl{\"a}rt werden. Die Befunde f{\"u}hrten zu weiteren Hypothesen hinsichtlich seiner funktionellen Einbindung in die olfaktorische Informationsverarbeitung, denen in zuk{\"u}nftigen Studien nachgegangen werden wird.},
  language  = {de}
}