@article{91246493c76845dcb804b6883e987e9e,
title = "A gradual temporal shift of dopamine responses mirrors the progression of temporal difference error in machine learning",
abstract = "A large body of evidence has indicated that the phasic responses of midbrain dopamine neurons show a remarkable similarity to a type of teaching signal (temporal difference (TD) error) used in machine learning. However, previous studies failed to observe a key prediction of this algorithm: that when an agent associates a cue and a reward that are separated in time, the timing of dopamine signals should gradually move backward in time from the time of the reward to the time of the cue over multiple trials. Here we demonstrate that such a gradual shift occurs both at the level of dopaminergic cellular activity and dopamine release in the ventral striatum in mice. Our results establish a long-sought link between dopaminergic activity and the TD learning algorithm, providing fundamental insights into how the brain associates cues and rewards that are separated in time.",
author = "Ryunosuke Amo and Sara Matias and Akihiro Yamanaka and Tanaka, {Kenji F.} and Naoshige Uchida and Mitsuko Watabe-Uchida",
note = "Funding Information: We thank I. Tsutsui-Kimura, H.-G. Kim and B. Babayan for technical assistance; V. Roser and S. Ikeda for assistance in animal training; H. Matsumoto for sharing data; A. Lowet, M. Bukwich and all laboratory members for discussion. We thank M. Mathis, E. Soucy, V. Murthy, M. Andermann and members of their laboratories for advice on establishing two-photon imaging of deep structures. We thank C. Dulac for sharing reagents and equipment. We thank D. Kim and the GENIE Project, Janelia Farm Research Campus, Howard Hughes Medical Institute, for pGP-CMV-GCaMP6f and pGP-AAV-CAG-FLEX-jGCaMP7f-WPRE plasmids; E. Boyden, Media Lab, Massachusetts Institute of Technology, for AAV5-CAG-FLEX-tdTomato and AAV5-CAG-tdTomato; K. Deisseroth, Stanford University, for pAAV-EF1a-DIO-hChR2(H134R)-EYFP-WPRE; and Y. Li, State Key Laboratory of Membrane Biology, Peking University, for AAV9-hSyn-DA2m. This work was supported by grants from the National Institute of Mental Health (R01MH125162, to M.W.-U.), the National Institutes of Health (U19 NS113201 and NS108740, to N.U.), the Simons Collaboration on Global Brain (to N.U.), the Japan Society for the Promotion of Science, Japan Science and Technology Agency (to R.A.), the Human Frontier Science Program (LT000801/2018, to S.M.), the Harvard Brain Science Initiative (HBI Young Scientist Transitions Award, to S.M.) and Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) by AMED (JP20dm0207069, to K.F.T.). Funding Information: We thank I. Tsutsui-Kimura, H.-G. Kim and B. Babayan for technical assistance; V. Roser and S. Ikeda for assistance in animal training; H. Matsumoto for sharing data; A. Lowet, M. Bukwich and all laboratory members for discussion. We thank M. Mathis, E. Soucy, V. Murthy, M. Andermann and members of their laboratories for advice on establishing two-photon imaging of deep structures. We thank C. Dulac for sharing reagents and equipment. We thank D. Kim and the GENIE Project, Janelia Farm Research Campus, Howard Hughes Medical Institute, for pGP-CMV-GCaMP6f and pGP-AAV-CAG-FLEX-jGCaMP7f-WPRE plasmids; E. Boyden, Media Lab, Massachusetts Institute of Technology, for AAV5-CAG-FLEX-tdTomato and AAV5-CAG-tdTomato; K. Deisseroth, Stanford University, for pAAV-EF1a-DIO-hChR2(H134R)-EYFP-WPRE; and Y. Li, State Key Laboratory of Membrane Biology, Peking University, for AAV9-hSyn-DA2m. This work was supported by grants from the National Institute of Mental Health (R01MH125162, to M.W.-U.), the National Institutes of Health (U19 NS113201 and NS108740, to N.U.), the Simons Collaboration on Global Brain (to N.U.), the Japan Society for the Promotion of Science, Japan Science and Technology Agency (to R.A.), the Human Frontier Science Program (LT000801/2018, to S.M.), the Harvard Brain Science Initiative (HBI Young Scientist Transitions Award, to S.M.) and Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) by AMED (JP20dm0207069, to K.F.T.). Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = aug,
doi = "10.1038/s41593-022-01109-2",
language = "English",
volume = "25",
pages = "1082--1092",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "8",
}