{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:00:07Z","timestamp":1790107207335,"version":"4.0.1"},"reference-count":66,"publisher":"Society for Neuroscience","issue":"49","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":332,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"the Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["21K06388"],"award-info":[{"award-number":["21K06388"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"the Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["19H03268"],"award-info":[{"award-number":["19H03268"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007449","name":"the Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"accepted":{"date-parts":[[2023,5,27]]},"published-print":{"date-parts":[[2023,12,6]]},"abstract":"<jats:p>\n                    Dopamine neurons (DANs) are extensively studied in the context of associative learning, in both vertebrates and invertebrates. In the acquisition of male and female\n                    <jats:italic>Drosophila<\/jats:italic>\n                    olfactory memory, the PAM cluster of DANs provides the reward signal, and the PPL1 cluster of DANs sends the punishment signal to the Kenyon cells (KCs) of mushroom bodies, the center for memory formation. However, thermo-genetical activation of the PPL1 DANs after memory acquisition impaired aversive memory, and that of the PAM DANs impaired appetitive memory. We demonstrate that the knockdown of glutamate decarboxylase, which catalyzes glutamate conversion to GABA in PAM DANs, potentiated the appetitive memory. In addition, the knockdown of glutamate transporter in PPL1 DANs potentiated aversive memory, suggesting that GABA and glutamate co-transmitters act in an inhibitory manner in olfactory memory formation. We also found that, in \u03b3KCs, the Rdl receptor for GABA and the mGluR DmGluRA mediate the inhibition. Although multiple-spaced training is required to form long-term aversive memory, a single cycle of training was sufficient to develop long-term memory when the glutamate transporter was knocked down, in even a single subset of PPL1 DANs. Our results suggest that the mGluR signaling pathway may set a threshold for memory acquisition to allow the organisms' behaviors to adapt to changing physiological conditions and environments.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    In the acquisition of olfactory memory in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , the PAM cluster of dopamine neurons (DANs) mediates the reward signal, while the PPL1 cluster of DANs conveys the punishment signal to the Kenyon cells of the mushroom bodies, which serve as the center for memory formation. We found that GABA co-transmitters in the PAM DANs and glutamate co-transmitters in the PPL1 DANs inhibit olfactory memory formation. Our findings demonstrate that long-term memory acquisition, which typically necessitates multiple-spaced training sessions to establish aversive memory, can be triggered with a single training cycle in cases where the glutamate co-transmission is inhibited, even within a single subset of PPL1 DANs, suggesting that the glutamate co-transmission may modulate the threshold for memory acquisition.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.2152-22.2023","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T12:35:12Z","timestamp":1689078912000},"page":"8294-8305","source":"Crossref","is-referenced-by-count":15,"title":["Combinatory Actions of Co-transmitters in Dopaminergic Systems Modulate\n                    <i>Drosophila<\/i>\n                    Olfactory Memories"],"prefix":"10.1523","volume":"43","author":[{"given":"Daisuke","family":"Yamazaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Maeyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8988-1884","authenticated-orcid":false,"given":"Tetsuya","family":"Tabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2023,7,10]]},"reference":[{"key":"2025111012001111000_43.49.8294.1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-021-00665-0"},{"key":"2025111012001111000_43.49.8294.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.038"},{"key":"2025111012001111000_43.49.8294.3","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14648"},{"key":"2025111012001111000_43.49.8294.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3611"},{"key":"2025111012001111000_43.49.8294.5","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.16135"},{"key":"2025111012001111000_43.49.8294.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2010.06.048"},{"key":"2025111012001111000_43.49.8294.7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002768"},{"key":"2025111012001111000_43.49.8294.8","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.04580"},{"key":"2025111012001111000_43.49.8294.9","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.04577"},{"key":"2025111012001111000_43.49.8294.10","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.49257"},{"key":"2025111012001111000_43.49.8294.11","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-08-02944.2000"},{"key":"2025111012001111000_43.49.8294.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.04.007"},{"key":"2025111012001111000_43.49.8294.13","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2175"},{"key":"2025111012001111000_43.49.8294.14","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1242\/dev.118.2.401","article-title":"Targeted gene expression as a means of altering cell fates and generating dominant phenotypes","volume":"118","author":"Brand","year":"1993","journal-title":"Development"},{"key":"2025111012001111000_43.49.8294.15","doi-asserted-by":"publisher","DOI":"10.1038\/nature11614"},{"key":"2025111012001111000_43.49.8294.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.08.034"},{"key":"2025111012001111000_43.49.8294.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.12.002"},{"key":"2025111012001111000_43.49.8294.18","doi-asserted-by":"publisher","DOI":"10.1101\/lm.5.1.38"},{"key":"2025111012001111000_43.49.8294.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.01.045"},{"key":"2025111012001111000_43.49.8294.20","doi-asserted-by":"crossref","first-page":"665386","DOI":"10.3389\/fncir.2021.665386","article-title":"Dopamine Neurons That Cotransmit Glutamate, From Synapses to Circuits to Behavior","volume":"15","author":"Eskenazi","year":"2021","journal-title":"Front Neural Circuit"},{"key":"2025111012001111000_43.49.8294.21","doi-asserted-by":"crossref","first-page":"7849","DOI":"10.1073\/pnas.89.16.7849-b","article-title":"Molecular cloning and transformation of cyclodiene resistance in Drosophila: An invertebrate \u03b3-amino-butyric acid subtype A receptor locus","volume":"89","author":"Ffrench-Constant","year":"1992","journal-title":"Proc National Acad Sci"},{"key":"2025111012001111000_43.49.8294.22","doi-asserted-by":"publisher","DOI":"10.1002\/neu.10185"},{"key":"2025111012001111000_43.49.8294.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.04.007"},{"key":"2025111012001111000_43.49.8294.24","doi-asserted-by":"publisher","DOI":"10.1038\/nature07001"},{"key":"2025111012001111000_43.49.8294.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.040"},{"key":"2025111012001111000_43.49.8294.26","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.neures.2017.05.002","article-title":"What can tiny mushrooms in fruit flies tell us about learning and memory?","volume":"129","author":"Hige","year":"2018","journal-title":"Neurosci Res"},{"key":"2025111012001111000_43.49.8294.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.11.003"},{"key":"2025111012001111000_43.49.8294.28","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227170"},{"key":"2025111012001111000_43.49.8294.29","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1099-11.2011"},{"key":"2025111012001111000_43.49.8294.30","unstructured":"Huang C , Luo J , Woo SJ , Roitman L , Li J , Pieribone V , Kannan M , Vasan G , Schnitzer M (2022) Dopamine signals integrate innate and learnt valences to regulate memory dynamics. Research Square."},{"key":"2025111012001111000_43.49.8294.31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122205699"},{"key":"2025111012001111000_43.49.8294.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.09.011"},{"key":"2025111012001111000_43.49.8294.33","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1347-12.2012"},{"key":"2025111012001111000_43.49.8294.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.06.022"},{"key":"2025111012001111000_43.49.8294.35","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1167-07.2007"},{"key":"2025111012001111000_43.49.8294.36","doi-asserted-by":"crossref","unstructured":"Kutlu MG , Tat J , Zachry JE , Calipari ES (2022) Dopamine release at the time of a predicted aversive outcome causally controls the trajectory and expression of conditioned behavior. BioRxiv 2022.04.15.488530.","DOI":"10.1101\/2022.04.15.488530"},{"key":"2025111012001111000_43.49.8294.37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019483108"},{"key":"2025111012001111000_43.49.8294.38","doi-asserted-by":"publisher","DOI":"10.1038\/nature11304"},{"key":"2025111012001111000_43.49.8294.39","doi-asserted-by":"publisher","DOI":"10.1126\/science.aal3245"},{"key":"2025111012001111000_43.49.8294.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.10.036"},{"key":"2025111012001111000_43.49.8294.41","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4763-08.2009"},{"key":"2025111012001111000_43.49.8294.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.08.028"},{"key":"2025111012001111000_43.49.8294.43","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.04.005.2009"},{"key":"2025111012001111000_43.49.8294.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.01.038"},{"key":"2025111012001111000_43.49.8294.45","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1126\/science.1089035","article-title":"Spatiotemporal rescue of memory dysfunction in Drosophila","volume":"302","author":"McGuire","year":"2003","journal-title":"Science (New York, NY)"},{"key":"2025111012001111000_43.49.8294.46","doi-asserted-by":"publisher","DOI":"10.1146\/ANNUREV-NEURO-080317-0621333"},{"key":"2025111012001111000_43.49.8294.47","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/s41586-023-06013-8","article-title":"Multisensory learning binds modality-specific neurons into a cross-modal memory engram","volume":"617","author":"Okray","year":"2023","journal-title":"Nature"},{"key":"2025111012001111000_43.49.8294.48","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-21-06687.1996"},{"key":"2025111012001111000_43.49.8294.49","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4542-03.2004"},{"key":"2025111012001111000_43.49.8294.50","doi-asserted-by":"publisher","DOI":"10.1126\/science.1226018"},{"key":"2025111012001111000_43.49.8294.51","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3055"},{"key":"2025111012001111000_43.49.8294.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2011.12.009"},{"key":"2025111012001111000_43.49.8294.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00432-0"},{"key":"2025111012001111000_43.49.8294.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.09.042"},{"key":"2025111012001111000_43.49.8294.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.03.032"},{"key":"2025111012001111000_43.49.8294.56","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-33-10495.2003"},{"key":"2025111012001111000_43.49.8294.57","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21692"},{"key":"2025111012001111000_43.49.8294.58","doi-asserted-by":"publisher","DOI":"10.1007\/BF01350033"},{"key":"2025111012001111000_43.49.8294.59","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90398-0"},{"key":"2025111012001111000_43.49.8294.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.10.007"},{"key":"2025111012001111000_43.49.8294.61","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.10.058"},{"key":"2025111012001111000_43.49.8294.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.02.059"},{"key":"2025111012001111000_43.49.8294.63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1421930112"},{"key":"2025111012001111000_43.49.8294.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.02.012"},{"key":"2025111012001111000_43.49.8294.65","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90399-9"},{"key":"2025111012001111000_43.49.8294.66","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5466.672"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.2152-22.2023","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.2152-22.2023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T20:00:25Z","timestamp":1762804825000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.2152-22.2023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,10]]},"references-count":66,"journal-issue":{"issue":"49","published-online":{"date-parts":[[2023,12,6]]},"published-print":{"date-parts":[[2023,12,6]]}},"alternative-id":["10.1523\/JNEUROSCI.2152-22.2023"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.2152-22.2023","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,10]]}}}