@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} } @article {45979, title = {Distinct dopamine neurons mediate reward signals for short- and long-term memories.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, year = {2015}, month = {2015 Jan 13}, pages = {578-83}, abstract = {

Drosophila melanogaster can acquire a stable appetitive olfactory memory when the presentation of a sugar reward and an odor are paired. However, the neuronal mechanisms by which a single training induces long-term memory are poorly understood. Here we show that two distinct subsets of dopamine neurons in the fly brain signal reward for short-term (STM) and long-term memories (LTM). One subset induces memory that decays within several hours, whereas the other induces memory that gradually develops after training. They convey reward signals to spatially segregated synaptic domains of the mushroom body (MB), a potential site for convergence. Furthermore, we identified a single type of dopamine neuron that conveys the reward signal to restricted subdomains of the mushroom body lobes and induces long-term memory. Constant appetitive memory retention after a single training session thus comprises two memory components triggered by distinct dopamine neurons.

}, issn = {1091-6490}, doi = {10.1073/pnas.1421930112}, author = {Yamagata, Nobuhiro and Ichinose, Toshiharu and Aso, Yoshinori and Placais, Pierre-Yves and Friedrich, Anja B and Sima, Richard J and Preat, Thomas and Rubin, Gerald M and Tanimoto, Hiromu} } @article {47182, title = {Reward signal in a recurrent circuit drives appetitive long-term memory formation.}, journal = {eLife}, volume = {4}, year = {2015}, month = {2015 Nov 18}, abstract = {

Dopamine signals reward in animal brains. A single presentation of a sugar reward to Drosophila activates distinct subsets of dopamine neurons that independently induce short- and long-term olfactory memories (STM and LTM, respectively). In this study, we show that a recurrent reward circuit underlies the formation and consolidation of LTM. This feedback circuit is composed of a single class of reward-signaling dopamine neurons (PAM-α1) projecting to a restricted region of the mushroom body (MB), and a specific MB output cell type, MBON-α1, whose dendrites arborize that same MB compartment. Both MBON-α1 and PAM-α1 neurons are required during the acquisition and consolidation of appetitive LTM. MBON-α1 additionally mediates the retrieval of LTM, which is dependent on the dopamine receptor signaling in the MB α/β neurons. Our results suggest that a reward signal transforms a nascent memory trace into a stable LTM using a feedback circuit at the cost of memory specificity.

}, issn = {2050-084X}, doi = {10.7554/eLife.10719}, author = {Ichinose, Toshiharu and Aso, Yoshinori and Yamagata, Nobuhiro and Abe, Ayako and Rubin, Gerald M and Tanimoto, Hiromu} } @article {45811, title = {Mushroom body output neurons encode valence and guide memory-based action selection in Drosophila.}, journal = {eLife}, volume = {4}, year = {2014}, month = {12/2014}, abstract = {

Animals discriminate stimuli, learn their predictive value and use this knowledge to modify their behavior. In Drosophila, the mushroom body (MB) plays a key role in these processes. Sensory stimuli are sparsely represented by \~{}2000 Kenyon cells, which converge onto 34 output neurons (MBONs) of 21 types. We studied the role of MBONs in several associative learning tasks and in sleep regulation, revealing the extent to which information flow is segregated into distinct channels and suggesting possible roles for the multi-layered MBON network. We also show that optogenetic activation of MBONs can, depending on cell type, induce repulsion or attraction in flies. The behavioral effects of MBON perturbation are combinatorial, suggesting that the MBON ensemble collectively represents valence. We propose that local, stimulus-specific dopaminergic modulation selectively alters the balance within the MBON network for those stimuli. Our results suggest that valence encoded by the MBON ensemble biases memory-based action selection.

}, issn = {2050-084X}, doi = {10.7554/eLife.04580}, author = {Aso, Yoshinori and Sitaraman, Divya and Ichinose, Toshiharu and Kaun, Karla R and Vogt, Katrin and Belliart-Gu{\'e}rin, Ghislain and Placais, Pierre-Yves and Robie, Alice A and Yamagata, Nobuhiro and Schnaitmann, Christopher and Rowell, William J and Johnston, Rebecca M and Ngo, Teri-T B and Chen, Nan and Korff, Wyatt and Nitabach, Michael N and Heberlein, Ulrike and Preat, Thomas and Branson, Kristin M and Tanimoto, Hiromu and Rubin, Gerald M} } @article {6300, title = {A subset of dopamine neurons signals reward for odour memory in Drosophila.}, journal = {Nature}, volume = {488}, year = {2012}, month = {2012 Aug 23}, pages = {512-6}, abstract = {

Animals approach stimuli that predict a pleasant outcome. After the paired presentation of an odour and a reward, Drosophila melanogaster can develop a conditioned approach towards that odour. Despite recent advances in understanding the neural circuits for associative memory and appetitive motivation, the cellular mechanisms for reward processing in the fly brain are unknown. Here we show that a group of dopamine neurons in the protocerebral anterior medial (PAM) cluster signals sugar reward by transient activation and inactivation of target neurons in intact behaving flies. These dopamine neurons are selectively required for the reinforcing property of, but not a reflexive response to, the sugar stimulus. In vivo calcium imaging revealed that these neurons are activated by sugar ingestion and the activation is increased on starvation. The output sites of the PAM neurons are mainly localized to the medial lobes of the mushroom bodies (MBs), where appetitive olfactory associative memory is formed. We therefore propose that the PAM cluster neurons endow a positive predictive value to the odour in the MBs. Dopamine in insects is known to mediate aversive reinforcement signals. Our results highlight the cellular specificity underlying the various roles of dopamine and the importance of spatially segregated local circuits within the MBs.

}, keywords = {Animals, Appetitive Behavior, Calcium Signaling, Dendrites, Dopamine, Dopaminergic Neurons, Drosophila melanogaster, Memory, Mushroom Bodies, Odors, Reward, Smell}, issn = {1476-4687}, doi = {10.1038/nature11304}, author = {Liu, Chang and Placais, Pierre-Yves and Yamagata, Nobuhiro and Pfeiffer, Barret D and Aso, Yoshinori and Friedrich, Anja B and Siwanowicz, Igor and Rubin, Gerald M and Preat, Thomas and Tanimoto, Hiromu} }