Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-18728 Dissertation Lyutova, Radostina Functional dissection of recurrent feedback signaling within the mushroom body network of the Drosophila larva Behavioral adaptation to environmental changes is crucial for animals' survival. The prediction of the outcome of one owns action, like finding reward or avoiding punishment, requires recollection of past experiences and comparison with current situation, and adjustment of behavioral responses. The process of memory acquisition is called learning, and the Drosophila larva came up to be an excellent model organism for studying the neural mechanisms of memory formation. In Drosophila, associative memories are formed, stored and expressed in the mushroom bodies. In the last years, great progress has been made in uncovering the anatomical architecture of these brain structures, however there is still a lack of knowledge about the functional connectivity. Dopamine plays essential roles in learning processes, as dopaminergic neurons mediate information about the presence of rewarding and punishing stimuli to the mushroom bodies. In the following work, the function of a newly identified anatomical connection from the mushroom bodies to rewarding dopaminergic neurons was dissected. A recurrent feedback signaling within the neuronal network was analyzed by simultaneous genetic manipulation of the mushroom body Kenyon cells and dopaminergic neurons from the primary protocerebral anterior (pPAM) cluster, and learning assays were performed in order to unravel the impact of the Kenyon cells-to-pPAM neurons feedback loop on larval memory formation. In a substitution learning assay, simultaneous odor exposure paired with optogenetic activation of Kenyon cells in fruit fly larvae in absence of a rewarding stimulus resulted in formation of an appetitive memory, whereas no learning behavior was observed when pPAM neurons were ablated in addition to the KC activation. I argue that the activation of Kenyon cells may induce an internal signal that mimics reward exposure by feedback activation of the rewarding dopaminergic neurons. My data further suggests that the Kenyon cells-to-pPAM communication relies on peptidergic signaling via short neuropeptide F and underlies memory stabilization. 2019 urn:nbn:de:bvb:20-opus-187281 10.25972/OPUS-18728 Graduate School of Life Sciences OPUS4-20216 Wissenschaftlicher Artikel Lyutova, Radostina; Selcho, Mareike; Pfeuffer, Maximilian; Segebarth, Dennis; Habenstein, Jens; Rohwedder, Astrid; Frantzmann, Felix; Wegener, Christian; Thum, Andreas S.; Pauls, Dennis Reward signaling in a recurrent circuit of dopaminergic neurons and peptidergic Kenyon cells Dopaminergic neurons in the brain of the Drosophila larva play a key role in mediating reward information to the mushroom bodies during appetitive olfactory learning and memory. Using optogenetic activation of Kenyon cells we provide evidence that recurrent signaling exists between Kenyon cells and dopaminergic neurons of the primary protocerebral anterior (pPAM) cluster. Optogenetic activation of Kenyon cells paired with odor stimulation is sufficient to induce appetitive memory. Simultaneous impairment of the dopaminergic pPAM neurons abolishes appetitive memory expression. Thus, we argue that dopaminergic pPAM neurons mediate reward information to the Kenyon cells, and in turn receive feedback from Kenyon cells. We further show that this feedback signaling is dependent on short neuropeptide F, but not on acetylcholine known to be important for odor-shock memories in adult flies. Our data suggest that recurrent signaling routes within the larval mushroom body circuitry may represent a mechanism subserving memory stabilization. 2019 3097 Nature Communications 10 urn:nbn:de:bvb:20-opus-202161 10.1038/s41467-019-11092-1 Institut für Klinische Neurobiologie