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Publication : The functional role of sequentially neuromodulated synaptic plasticity in behavioural learning.

First Author  Ang GWY Year  2021
Journal  PLoS Comput Biol Volume  17
Issue  6 Pages  e1009017
PubMed ID  34111110 Mgi Jnum  J:355628
Mgi Id  MGI:7748921 Doi  10.1371/journal.pcbi.1009017
Citation  Ang GWY, et al. (2021) The functional role of sequentially neuromodulated synaptic plasticity in behavioural learning. PLoS Comput Biol 17(6):e1009017
abstractText  To survive, animals have to quickly modify their behaviour when the reward changes. The internal representations responsible for this are updated through synaptic weight changes, mediated by certain neuromodulators conveying feedback from the environment. In previous experiments, we discovered a form of hippocampal Spike-Timing-Dependent-Plasticity (STDP) that is sequentially modulated by acetylcholine and dopamine. Acetylcholine facilitates synaptic depression, while dopamine retroactively converts the depression into potentiation. When these experimental findings were implemented as a learning rule in a computational model, our simulations showed that cholinergic-facilitated depression is important for reversal learning. In the present study, we tested the model's prediction by optogenetically inactivating cholinergic neurons in mice during a hippocampus-dependent spatial learning task with changing rewards. We found that reversal learning, but not initial place learning, was impaired, verifying our computational prediction that acetylcholine-modulated plasticity promotes the unlearning of old reward locations. Further, differences in neuromodulator concentrations in the model captured mouse-by-mouse performance variability in the optogenetic experiments. Our line of work sheds light on how neuromodulators enable the learning of new contingencies.
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