@article {64815, title = {Neuronal reactivation during post-learning sleep consolidates long-term memory in .}, journal = {eLife}, volume = {8}, year = {2019}, month = {2019 Feb 25}, abstract = {

Animals consolidate some, but not all, learning experiences into long-term memory. Across the animal kingdom, sleep has been found to have a beneficial effect on the consolidation of recently formed memories into long-term storage. However, the underlying mechanisms of sleep dependent memory consolidation are poorly understood. Here, we show that consolidation of courtship long-term memory in is mediated by reactivation during sleep of dopaminergic neurons that were earlier involved in memory acquisition. We identify specific fan-shaped body neurons that induce sleep after the learning experience and activate dopaminergic neurons for memory consolidation. Thus, we provide a direct link between sleep, neuronal reactivation of dopaminergic neurons, and memory consolidation.

}, issn = {2050-084X}, doi = {10.7554/eLife.42786}, author = {Dag, Ugur and Lei, Zhengchang and Le, Jasmine Q and Wong, Allan and Bushey, Daniel and Keleman, Krystyna} } @article {49002, title = {Persistent activity in a recurrent circuit underlies courtship memory in Drosophila.}, journal = {eLife}, volume = {7}, year = {2018}, month = {2018 Jan 11}, abstract = {

Recurrent connections are thought to be a common feature of the neural circuits that encode memories, but how memories are laid down in such circuits is not fully understood. Here we present evidence that courtship memory in Drosophila relies on the recurrent circuit between mushroom body gamma (MBg), M6 output, and aSP13 dopaminergic neurons. We demonstrate persistent neuronal activity of aSP13 neurons and show that it transiently potentiates synaptic transmission from MBγ\>M6 neurons. M6 neurons in turn provide input to aSP13 neurons, prolonging potentiation of MBγ\>M6 synapses over time periods that match short-term memory. These data support a model in which persistent aSP13 activity within a recurrent circuit lays the foundation for a short-term memory.

}, issn = {2050-084X}, doi = {10.7554/eLife.31425}, author = {Zhao, Xiaoliang and Lenek, Daniela and Dag, Ugur and Dickson, Barry and Keleman, Krystyna} } @article {48069, title = {RNA-binding profiles of Drosophila CPEB proteins Orb and Orb2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2016}, month = {2016 Oct 24}, abstract = {

Localized protein translation is critical in many biological contexts, particularly in highly polarized cells, such as neurons, to regulate gene expression in a spatiotemporal manner. The cytoplasmic polyadenylation element-binding (CPEB) family of RNA-binding proteins has emerged as a key regulator of mRNA transport and local translation required for early embryonic development, synaptic plasticity, and long-term memory (LTM). Drosophila Orb and Orb2 are single members of the CPEB1 and CPEB2 subfamilies of the CPEB proteins, respectively. At present, the identity of the mRNA targets they regulate is not fully known, and the binding specificity of the CPEB2 subfamily is a matter of debate. Using transcriptome-wide UV cross-linking and immunoprecipitation, we define the mRNA-binding sites and targets of Drosophila CPEBs. Both Orb and Orb2 bind linear cytoplasmic polyadenylation element-like sequences in the 3{\textquoteright} UTRs of largely overlapping target mRNAs, with Orb2 potentially having a broader specificity. Both proteins use their RNA-recognition motifs but not the Zinc-finger region for RNA binding. A subset of Orb2 targets is translationally regulated in cultured S2 cells and fly head extracts. Moreover, pan-neuronal RNAi knockdown of these targets suggests that a number of these targets are involved in LTM. Our results provide a comprehensive list of mRNA targets of the two CPEB proteins in Drosophila, thus providing insights into local protein synthesis involved in various biological processes, including LTM.

}, issn = {1091-6490}, doi = {10.1073/pnas.1603715113}, author = {Stepien, Barbara Krystyna and Oppitz, Cornelia and Gerlach, Daniel and Dag, Ugur and Novatchkova, Maria and Kr{\"u}ttner, Sebastian and Stark, Alexander and Keleman, Krystyna} } @article {46887, title = {Synaptic Orb2A bridges memory acquisition and late memory consolidation in Drosophila.}, journal = {Cell Reports}, volume = {11}, year = {2015}, month = {2015 Jun 30}, pages = {1953-65}, abstract = {

To adapt to an ever-changing environment, animals consolidate some, but not all, learning experiences to long-term memory. In mammals, long-term memory consolidation often involves neural pathway reactivation hours after memory acquisition. It is not known whether this delayed-reactivation schema is\ common across the animal kingdom or how information is stored during the delay period. Here, we show\ that, during courtship suppression learning, Drosophila exhibits delayed long-term memory consolidation. We also show that the same class of dopaminergic neurons engaged earlier in memory acquisition is also both necessary and sufficient for delayed long-term memory consolidation. Furthermore, we present evidence that, during learning, the translational regulator Orb2A tags specific synapses of mushroom body neurons for later consolidation. Consolidation involves the subsequent recruitment of Orb2B and the activity-dependent synthesis of CaMKII. Thus, our results provide evidence for the role of a neuromodulated, synapse-restricted molecule bridging memory acquisition and long-term memory consolidation in a learning animal.

}, issn = {2211-1247}, doi = {10.1016/j.celrep.2015.05.037}, author = {Kr{\"u}ttner, Sebastian and Traunm{\"u}ller, Lisa and Dag, Ugur and Jandrasits, Katharina and Stepien, Barbara and Iyer, Nirmala and Fradkin, Lee G and Noordermeer, Jasprina N and Mensh, Brett D and Keleman, Krystyna} }