Graduate School of Innovative Life Science, University of Toyama, Gofuku, Toyama, Japan.
Department of Pharmaceutical Sciences, School of Health & Life Sciences, North South University, Dhaka, Bangladesh.
PLoS One. 2020 Aug 13;15(8):e0237451. doi: 10.1371/journal.pone.0237451. eCollection 2020.
The serial feature-positive discrimination task requires the subjects to respond differentially to the identical stimulus depending on the temporal context given by a preceding cue stimulus. In the present study, we examined the involvement of the M1 muscarinic acetylcholine receptors using a selective M1 antagonist VU0255035 in the serial feature-positive discrimination task of eyeblink conditioning in mice. In this task, mice received a 2-s light stimulus as the conditional cue 5 or 6 s before the presentation of a 350-ms tone conditioned stimulus (CS) paired with a 100-ms peri-orbital electrical shock (cued trials), while they did not receive the cue before the presentation of the CS alone (non-cued trials). Each day mice randomly received 30 cued and 30 non-cued trials. We found that VU0255035 impaired acquisition of the conditional discrimination as well as the overall acquisition of the conditioned response (CR) and diminished the difference in onset latency of the CR between the cued and non-cued trials. VU0255035 administration to the control mice after sufficient learning did not impair the pre-acquired conditional discrimination or the CR expression itself. These effects of VU0255035 were almost similar to those with the scopolamine in our previous study, suggesting that among the several types of muscarinic acetylcholine receptors, the M1 receptors may play an important role in the acquisition of the conditional discrimination memory but not in mediating the discrimination itself after the memory had formed in the eyeblink serial feature-positive discrimination learning.
序列特征正辨别任务要求受试者根据前导提示刺激提供的时间上下文，对相同的刺激做出不同的反应。在本研究中，我们使用选择性 M1 拮抗剂 VU0255035，在小鼠的眨眼条件反射序列特征正辨别任务中，研究了 M1 毒蕈碱乙酰胆碱受体的参与。在这个任务中，小鼠在呈现 350ms 音调条件刺激（CS）之前 5 或 6s 接收到 2s 的光刺激作为条件提示（提示试验），而在 CS 单独呈现之前，它们不会接收到提示（非提示试验）。每天，老鼠随机接受 30 个提示试验和 30 个非提示试验。我们发现，VU0255035 损害了条件辨别以及条件反应（CR）的整体获得，并降低了提示和非提示试验之间 CR 起始潜伏期的差异。在充分学习后，VU0255035 给药到对照组小鼠中，并没有损害预先获得的条件辨别或 CR 表达本身。VU0255035 的这些作用与我们之前研究中的东莨菪碱的作用几乎相似，表明在几种类型的毒蕈碱乙酰胆碱受体中，M1 受体可能在条件辨别记忆的获得中发挥重要作用，但在眨眼序列特征正辨别学习中记忆形成后，并不介导辨别本身。
