Department of Neuroscience, Erasmus MC Rotterdam, Rotterdam 3015 GD, The Netherlands.
Royal Dutch Academy of Arts & Science (KNAW), Netherlands Institute for Neuroscience, Amsterdam 1105 BA, The Netherlands.
eNeuro. 2022 Mar 22;9(2). doi: 10.1523/ENEURO.0400-21.2022. Print 2022 Mar-Apr.
Here, we investigate stimulus generalization in a cerebellar learning paradigm, called eyeblink conditioning. Mice were conditioned to close their eyes in response to a 10-kHz tone by repeatedly pairing this tone with an air puff to the eye 250 ms after tone onset. After 10 consecutive days of training, when mice showed reliable conditioned eyelid responses to the 10-kHz tone, we started to expose them to tones with other frequencies, ranging from 2 to 20 kHz. We found that mice had a strong generalization gradient, whereby the probability and amplitude of conditioned eyelid responses gradually decreases depending on the dissimilarity with the 10-kHz tone. Tones with frequencies closest to 10 kHz evoked the most and largest conditioned eyelid responses and each step away from the 10-kHz tone resulted in fewer and smaller conditioned responses (CRs). In addition, we found that tones with lower frequencies resulted in CRs that peaked earlier after tone onset compared with those to tones with higher frequencies. Together, our data show prominent generalization patterns in cerebellar learning. Since the known function of cerebellum is rapidly expanding from pure motor control to domains that include cognition, reward-learning, fear-learning, social function, and even addiction, our data imply generalization controlled by cerebellum in all these domains.
在这里,我们研究了一种称为眨眼条件反射的小脑学习范式中的刺激泛化。通过在音调出现后 250 毫秒重复将该音调与眼部空气喷射配对,使小鼠对 10 kHz 音调做出闭眼反应,从而对其进行条件训练。经过 10 天的连续训练,当小鼠对 10 kHz 音调表现出可靠的条件性眨眼反应时,我们开始让它们接触其他频率的音调,范围从 2 到 20 kHz。我们发现,小鼠具有很强的泛化梯度,条件性眨眼反应的概率和幅度逐渐降低,这取决于与 10 kHz 音调的相似性。频率最接近 10 kHz 的音调会引起最多和最大的条件性眨眼反应,而每远离 10 kHz 音调一步,都会导致更少和更小的条件反应 (CR)。此外,我们发现,与高频音调相比,低频音调引起的 CR 在音调出现后更早达到峰值。总之,我们的数据显示小脑学习中存在明显的泛化模式。由于小脑的已知功能正在从纯运动控制迅速扩展到包括认知、奖励学习、恐惧学习、社交功能甚至成瘾等领域,我们的数据意味着小脑在所有这些领域中都控制着泛化。