The functional role of sequentially neuromodulated synaptic plasticity in behavioural learning.
The functional role of sequentially neuromodulated synaptic plasticity in behavioural learning.
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DOI：
10.1371/journal.pcbi.1009017
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发表时间：
2021-06
影响因子：
4.3
通讯作者：
Clopath C
中科院分区：
文献类型：
--
作者：
Ang GWY;Tang CS;Hay YA;Zannone S;Paulsen O;Clopath C
为了生存，动物必须在奖励改变时迅速改变它们的行为。负责这一点的内部表征通过突触权重变化进行更新，由某些神经调节剂传递来自环境的反馈。在以前的实验中，我们发现了一种形式的海马尖峰定时依赖性可塑性（STDP），这是由乙酰胆碱和多巴胺顺序调制。乙酰胆碱促进突触抑制，而多巴胺追溯性地将抑制转化为增强。当这些实验结果在计算模型中作为学习规则实施时，我们的模拟表明，胆碱能促进的抑郁症对逆转学习很重要。在本研究中，我们测试了模型的预测，通过光遗传学失活小鼠胆碱能神经元在一个依赖于大脑皮层的空间学习任务与变化的奖励。我们发现，逆转学习，但不是初始位置的学习，受损，验证了我们的计算预测，乙酰胆碱调制的可塑性促进旧的奖励位置的遗忘。此外，模型中神经调节剂浓度的差异在光遗传学实验中捕获了小鼠与小鼠之间的性能变异性。我们的工作揭示了神经调节剂如何使新的偶然性的学习。重复学习可能涉及突触连接的变化，这是一种被称为突触可塑性的神经机制，因此旧的信息可以更新。我们之前发现乙酰胆碱，一种重要的大脑神经调节剂，以一种有利于逆转学习的方式改变突触连接。具体来说，乙酰胆碱削弱了大脑切片中活跃的突触，但这些突触后来可以通过奖励信号得到加强。基于切片的结果，我们使用了一个计算模型，提出了乙酰胆碱对突触连接作用的行为函数。在这个模型中，乙酰胆碱会削弱与旧奖励相关的突触连接，使智能体能够快速学习新的奖励位置。我们在这里通过沉默小鼠的乙酰胆碱神经元来验证这一假设，同时它们在迷宫中导航以获得食物奖励。这些动物能够学习第一次食物奖励的位置，但当奖励被转移到新的位置时，它们就会受到损害。这项研究的行为结果表明，乙酰胆碱确实促进了逆转学习，计算模型将其归因于突触连接的减弱，而这种连接不会导致奖励。综上所述，我们的实验和计算工作显示了突触强度的变化，由神经调质门控，影响学习行为。
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. Reversal learning likely involves changes in synaptic connections, a neural mechanism known as synaptic plasticity, so old information can be updated. We previously discovered that acetylcholine, an important neuromodulator in the brain, changes synaptic connections in a way that favours reversal learning. Specifically, acetylcholine weakens active synapses in brain slices, but these synapses can later be strengthened by a reward signal. Based on this result in slices, we used a computational model to propose a behavioural function for the action of acetylcholine on synaptic connections. In the model, acetylcholine would weaken synaptic connections associated with an old reward, allowing an agent to quickly learn a new reward location. We tested this hypothesis here by silencing acetylcholine neurons in mice while they navigated a maze for food rewards. These animals were able to learn the location of the first food reward, but were impaired when the reward was shifted to a new location. The behavioural results of this study suggest that acetylcholine indeed facilitates reversal learning, which the computational model attributes to a weakening of synaptic connections that do not lead to reward. Taken together, our experimental and computational work show how synaptic strength changes, gated by neuromodulators, affect learning behaviour.
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