title: Retroactive modulation of spike timing-dependent plasticity by dopamine.
abstract: Most reinforcement learning models assume that the reward signal arrives after the activity that led to the reward, placing constraints on the possible underlying cellular mechanisms. Here we show that dopamine, a positive reinforcement signal, can retroactively convert hippocampal timing-dependent synaptic depression into potentiation. This effect requires functional NMDA receptors and is mediated in part through the activation of the cAMP/PKA cascade. Collectively, our results support the idea that reward-related signaling can act on a pre-established synaptic eligibility trace, thereby associating specific experiences with behaviorally distant, rewarding outcomes. This finding identifies a biologically plausible mechanism for solving the 'distal reward problem'.
authors.affiliation: Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Brzosko
authors.affiliation: Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Schultz
authors.affiliation: Department of Physiology, Development and Neuroscience, Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Ole
authors.identifier: http://orcid.org/0000-0002-2258-5455
authors.initials: O
authors.lastname: Paulsen
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012054:Reinforcement, Psychology; D015398:Signal Transduction
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D004298:Dopamine
keywords: dopamine; mouse; neuroscience; reward; synaptic plasticity