title: Distinct Eligibility Traces for LTP and LTD in Cortical Synapses.
abstract: In reward-based learning, synaptic modifications depend on a brief stimulus and a temporally delayed reward, which poses the question of how synaptic activity patterns associate with a delayed reward. A theoretical solution to this so-called distal reward problem has been the notion of activity-generated "synaptic eligibility traces," silent and transient synaptic tags that can be converted into long-term changes in synaptic strength by reward-linked neuromodulators. Here we report the first experimental demonstration of eligibility traces in cortical synapses. We demonstrate the Hebbian induction of distinct traces for LTP and LTD and their subsequent timing-dependent transformation into lasting changes by specific monoaminergic receptors anchored to postsynaptic proteins. Notably, the temporal properties of these transient traces allow stable learning in a recurrent neural network that accurately predicts the timing of the reward, further validating the induction and transformation of eligibility traces for LTP and LTD as a plausible synaptic substrate for reward-based learning.
authors.affiliation: Mind/Brain Institute, Johns Hopkins University, 3400 North Charles Street, 350 Dunning Hall, Baltimore, MD 21218, USA.
authors.forename: Kaiwen
authors.initials: K
authors.lastname: He
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas at Houston, 6431 Fannin Street, Suite MSB 7.046, Houston, TX 77030, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Huertas
authors.affiliation: Mind/Brain Institute, Johns Hopkins University, 3400 North Charles Street, 350 Dunning Hall, Baltimore, MD 21218, USA.
authors.forename: Su Z
authors.initials: SZ
authors.lastname: Hong
authors.affiliation: Mind/Brain Institute, Johns Hopkins University, 3400 North Charles Street, 350 Dunning Hall, Baltimore, MD 21218, USA.
authors.forename: XiaoXiu
authors.initials: X
authors.lastname: Tie
authors.affiliation: Department of Pharmacology, University of California, Davis, 1544 Newton Court, Davis, CA 95618, USA.
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Hell
authors.affiliation: Department of Neurobiology and Anatomy, University of Texas at Houston, 6431 Fannin Street, Suite MSB 7.046, Houston, TX 77030, USA.
authors.forename: Harel
authors.initials: H
authors.lastname: Shouval
authors.affiliation: Mind/Brain Institute, Johns Hopkins University, 3400 North Charles Street, 350 Dunning Hall, Baltimore, MD 21218, USA. Electronic address: kirkwood@jhu.edu.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Kirkwood
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D062308:Optogenetics / Q000379:methods; D009924:Organ Culture Techniques; D013569:Synapses / Q000502:physiology*