School of Psychology, University of Nottingham, Nottingham, UK.
Brain Behav. 2018 Dec;8(12):e01147. doi: 10.1002/brb3.1147. Epub 2018 Oct 31.
Trace conditioning is impaired by lesions to dorsal hippocampus, as well as by treatment with the muscarinic acetylcholine antagonist scopolamine. However, the role of muscarinic receptors within hippocampus has received little attention.
The present study examined the effects of intra-hippocampal infusion of scopolamine (30 µg/side) in an appetitive (2 vs. 10 s) trace conditioning procedure using sucrose pellets as the unconditioned stimulus (US). Locomotor activity (LMA) was examined in a different apparatus.
Intra-hippocampal scopolamine reduced responding to the 2 s trace conditioned stimulus (CS). Intra-hippocampal scopolamine similarly depressed responding within the inter-stimulus interval (ISI) at both 2 and 10 s trace intervals, but there was no such effect in the inter-trial interval. There was also some overall reduction in responding when the US was delivered; significant at the 10 s but not at the 2 s trace interval. A similar pattern of results to that seen in response to the CS during acquisition was shown drug-free (in the 5 s post-CS) in the extinction tests of conditioned responding. LMA was increased under scopolamine.
The results suggest that nonspecific changes in activity or motivation to respond for the US cannot explain the reduction in trace conditioning as measured by reduced CS responding and in the ISI. Rather, the findings of the present study point to the importance of associative aspects of the task in determining its sensitivity to the effects of scopolamine, suggesting that muscarinic receptors in the hippocampus are important modulators of short-term working memory.
痕迹条件反射会因背侧海马体损伤以及使用毒蕈碱乙酰胆碱拮抗剂东莨菪碱治疗而受损。然而,海马体内的毒蕈碱受体的作用却很少受到关注。
本研究使用蔗糖丸作为非条件刺激(US),在一种奖赏性(2 秒与 10 秒)痕迹条件反射程序中,检查了内侧海马内注射东莨菪碱(30μg/侧)的作用。在另一个装置中检查了运动活动(LMA)。
内侧海马内的东莨菪碱减少了对 2 秒痕迹条件刺激(CS)的反应。内侧海马内的东莨菪碱同样在 2 秒和 10 秒痕迹间隔的刺激间隔内抑制了反应,但在试验间隔内没有这种作用。当 US 被给予时,也会导致整体反应减少;在 10 秒痕迹间隔时显著,但在 2 秒痕迹间隔时不显著。在条件反应的消退测试中,药物自由(CS 后 5 秒)时,也显示出与在获得过程中对 CS 的反应相似的结果。LMA 在东莨菪碱下增加。
研究结果表明,对于 US 的活动或反应动机的非特异性变化不能解释由于 CS 反应减少和 ISI 减少而导致的痕迹条件反射的减少。相反,本研究的结果表明,任务的联想方面在确定其对东莨菪碱的敏感性方面的重要性,这表明海马体内的毒蕈碱受体是短期工作记忆的重要调节剂。