Distinct Eligibility Traces for LTP and LTD in Cortical Synapses

• Published in: Neuron (Cambridge, Mass.) Mass.), 2015-11, Vol.88 (3), p.528-538
• Main Authors: He, Kaiwen, Huertas, Marco, Hong, Su Z., Tie, XiaoXiu, Hell, Johannes W., Shouval, Harel, Kirkwood, Alfredo
• Format: Article
• Language: English
• Subjects: Animals; Cerebral Cortex - physiology; Long-Term Potentiation - physiology; Long-Term Synaptic Depression - physiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neural networks; Neuronal Plasticity; Optogenetics - methods; Organ Culture Techniques; Rodents; Synapses - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2015.09.037

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. •Hebbian conditioning induces eligibility traces for LTP and LTD in cortical synapses•β2ARs and 5-HT2CRs convert the traces into LTP and LTD, respectively•Anchoring of β2ARs and 5-HT2C is key for trace conversion•Temporal properties of the LTP/D traces allow reward-timing prediction How is stimulus-evoked activity associated with a time-delayed reward in reinforcement learning? He et al. report on the existence of silent and transient synaptic tags (eligibility traces) that can be converted into long-term changes in synaptic strength by reward-linked neuromodulators.