@article {65637, title = {Identification of dopaminergic neurons that can both establish associative memory and acutely terminate its behavioral expression.}, journal = {Journal of Neuroscience}, volume = {40}, year = {2020}, month = {2020 Jul 29}, pages = {5990-6006}, abstract = {

An adaptive transition from exploring the environment in search of vital resources to exploiting these resources once the search is successful is important to all animals. Here we study the neuronal circuitry that allows larval of either sex to negotiate this exploration-exploitation transition. We do so by combining Pavlovian conditioning with high-resolution behavioral tracking, optogenetic manipulation of individually identified neurons, and EM-data-based analyses of synaptic organization. We find that optogenetic activation of the dopaminergic neuron DAN-i1 can both establish memory during training, and acutely terminate learned search behavior in a subsequent recall test. Its activation leaves innate behavior unaffected, however. Specifically, DAN-i1 activation can establish associative memories of opposite valence upon paired and unpaired training with odor, and its activation during the recall test can terminate the search behavior resulting from either of these memories. Our results further suggest that in its behavioral significance DAN-i1 activation resembles but does not equal sugar reward. Dendrogram analyses of all the synaptic connections between DAN-i1 and its two main targets, the Kenyon cells and the mushroom body output neuron MBON-i1, further suggest that the DAN-i1 signals during training and during the recall test could be delivered to the Kenyon cells and to MBON-i1, respectively, within previously unrecognized, locally confined branching structures. This would provide an elegant circuit motif to terminate search upon its successful completion.In the struggle for survival animals have to explore their environment in search of food. Once food is found, however, it is adaptive to prioritize exploiting it over continuing a search that would now be as pointless as searching for the glasses you are wearing. This exploration-exploitation trade-off is important for animals and humans, as well as for technical search devices. We investigate which of the only 10,000 neurons of a fruit fly larva can tip the balance in this trade-off, and identify a single dopamine neuron called DAN-i1 that can do so. Given the similarities in dopamine neuron function across the animal kingdom, this may reflect a general principle of how search is terminated once it is successful.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.0290-20.2020}, author = {Schleyer, Michael and Weiglein, Ali{\'c}e and Thoener, Juliane and Strauch, Martin and Hartenstein, Volker and Kantar Weigelt, Melisa and Schuller, Sarah and Saumweber, Timo and Eichler, Katharina and Rohwedder, Astrid and Merhof, Dorit and Zlatic, Marta and Thum, Andreas S and Gerber, Bertram} } @article {49093, title = {Functional architecture of reward learning in mushroom body extrinsic neurons of larval Drosophila.}, journal = {Nature Communications}, volume = {9}, year = {2018}, month = {2018 Mar 16}, pages = {1104}, abstract = {

The brain adaptively integrates present sensory input, past experience, and options for future action. The insect mushroom body exemplifies how a central brain structure brings about such integration. Here we use a combination of systematic single-cell labeling, connectomics, transgenic silencing, and activation experiments to study the mushroom body at single-cell resolution, focusing on the behavioral architecture of its input and output neurons (MBINs and MBONs), and of the mushroom body intrinsic APL neuron. Our results reveal the identity and morphology of almost all of these 44 neurons in stage 3 Drosophila larvae. Upon an initial screen, functional analyses focusing on the mushroom body medial lobe uncover sparse and specific functions of its dopaminergic MBINs, its MBONs, and of the GABAergic APL neuron across three behavioral tasks, namely odor preference, taste preference, and associative learning between odor and taste. Our results thus provide a cellular-resolution study case of how brains organize behavior.

}, issn = {2041-1723}, doi = {10.1038/s41467-018-03130-1}, author = {Saumweber, Timo and Rohwedder, Astrid and Schleyer, Michael and Eichler, Katharina and Chen, Yi-chun and Aso, Yoshinori and Cardona, Albert and Eschbach, Claire and Kobler, Oliver and Voigt, Anne and Durairaja, Archana and Mancini, Nino and Zlatic, Marta and Truman, James W and Thum, Andreas S and Gerber, Bertram} } @article {47303, title = {Four individually identified paired dopamine neurons signal reward in larval Drosophila.}, journal = {Current Biology : CB}, year = {2016}, month = {2016 Feb 10}, abstract = {

Dopaminergic neurons serve multiple functions, including reinforcement processing during associative learning [1-12]. It is thus warranted to understand which dopaminergic neurons mediate which function. We study larval Drosophila, in which only approximately 120 of a total of 10,000 neurons are dopaminergic, as judged by the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine biosynthesis [5, 13]. Dopaminergic neurons mediating reinforcement in insect olfactory learning target the mushroom bodies, a higher-order "cortical" brain region [1-5, 11, 12, 14, 15]. We discover four previously undescribed paired neurons, the primary protocerebral anterior medial (pPAM) neurons. These neurons are TH positive and subdivide the medial lobe of the mushroom body into four distinct subunits. These pPAM neurons are acutely necessary for odor-sugar reward learning and require intact TH function in this process. However, they are dispensable for aversive learning and innate behavior toward the odors and sugars employed. Optogenetical activation of pPAM neurons is sufficient as a reward. Thus, the pPAM neurons convey a likely dopaminergic reward signal. In contrast, DL1 cluster neurons convey a corresponding punishment signal [5], suggesting a cellular division of labor to convey dopaminergic reward and punishment signals. On the level of individually identified neurons, this uncovers an organizational principle shared with adult Drosophila and mammals [1-4, 7, 9, 10] (but see [6]). The numerical simplicity and connectomic tractability of the larval nervous system [16-19] now offers a prospect for studying circuit principles of dopamine function at unprecedented resolution.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2016.01.012}, author = {Rohwedder, Astrid and Wenz, Nana L and Stehle, Bernhard and Huser, Annina and Yamagata, Nobuhiro and Zlatic, Marta and Truman, James W and Tanimoto, Hiromu and Saumweber, Timo and Gerber, Bertram and Thum, Andreas S} }