The functional role of sequentially neuromodulated synaptic plasticity in behavioural learning

• Published in: PLoS computational biology Vol. 17; no. 6; p. e1009017
• Main Authors: Ang, Grace Wan Yu, Tang, Clara S, Hay, Y Audrey, Zannone, Sara, Paulsen, Ole, Clopath, Claudia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2021; PLOS; Public Library of Science (PLoS)
• Subjects: Acetylcholine; Animal behavior; Animals; Behavior, Animal; Biology and Life Sciences; Cholinergic Neurons - physiology; Cholinergics; Cognitive Sciences; Cognitive tasks; Computational neuroscience; Dopamine; Experiments; Firing pattern; Food; Hippocampal plasticity; Hippocampus; Learning; Learning - physiology; Life Sciences; Long-Term Potentiation - physiology; Mice; Model testing; Models, Neurological; Neural networks; Neurological research; Neuromodulation; Neuronal Plasticity - physiology; Neurons and Cognition; Neuroplasticity; Neurotransmitter Agents - physiology; Physical Sciences; Plasticity; Potentiation; Reinforcement; Reversal learning; Reward; Social Sciences; Spatial discrimination learning; Success; Synaptic depression; Synaptic plasticity; Synaptic strength; Synaptic Transmission - physiology; United Kingdom
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1009017

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.