Wilson David I G, MacLaren Duncan A A, Winn Philip
School of Psychology, University of St Andrews, St Mary's Quad, St Andrews, Fife, UK.
Eur J Neurosci. 2009 Aug;30(3):504-13. doi: 10.1111/j.1460-9568.2009.06836.x. Epub 2009 Jul 15.
The pedunculopontine tegmental nucleus (PPTg) is in a key position to participate in operant reinforcement via its connections with the corticostriatal architecture and the medial reticular formation. Indeed, previous work has demonstrated that rats bearing lesions of the whole PPTg are impaired when learning to make two bar presses for amphetamine reinforcement. Anterior and posterior portions of the PPTg make different anatomical connections, including preferential projections by the anterior PPTg to substantia nigra pars compacta dopamine neurons and by the posterior PPTg to ventral tegmental area dopamine neurons. We wanted to assess the effects of anterior and posterior PPTg ibotenate lesions on rats learning simple and more complex schedules of natural reinforcement. We trained rats with lesions to the anterior PPTg (n = 11) and the posterior PPTg (n = 5) [and appropriate controls (n = 15)] to bar press for food on a variety of fixed-ratio and variable-ratio reinforcement schedules and then during extinction. We found that posterior PPTg-lesioned rats bar pressed at lower rates, were slower to learn to bar press, and often had deficits characteristic of impaired learning and/or motivation. In contrast, anterior PPTg-lesioned rats learned to bar press for reinforcement at normal rates. However, they made errors of perseveration and anticipation throughout many schedules, and pressed at a higher rate than controls during extinction, deficits best characterized as reflecting disorganized response control. Together, these data suggest that the anterior PPTg and posterior PPTg (and their related circuits) contribute differently to reinforcement learning, incentive motivation, and response control, processes that are considered to malfunction in drug addiction.
脚桥被盖核(PPTg)通过其与皮质纹状体结构和内侧网状结构的连接,处于参与操作性强化的关键位置。事实上,先前的研究表明,整个PPTg受损的大鼠在学习为获得苯丙胺强化而进行两次压杆操作时会受到损害。PPTg的前部和后部形成不同的解剖学连接,包括前部PPTg优先投射到黑质致密部多巴胺能神经元,后部PPTg优先投射到腹侧被盖区多巴胺能神经元。我们想评估PPTg前部和后部注射鹅膏蕈氨酸损伤对大鼠学习简单和更复杂自然强化程序的影响。我们训练了前部PPTg损伤的大鼠(n = 11)、后部PPTg损伤的大鼠(n = 5)[以及适当的对照组(n = 15)],使其在各种固定比率和可变比率强化程序下为获取食物进行压杆操作,然后进行消退训练。我们发现,后部PPTg损伤的大鼠压杆频率较低,学习压杆的速度较慢,并且经常出现学习和/或动机受损的特征性缺陷。相比之下,前部PPTg损伤的大鼠以正常速度学习为获得强化而进行压杆操作。然而,在许多程序中,它们都出现了持续和预期错误,并且在消退期间的压杆频率高于对照组,这些缺陷最能反映出反应控制紊乱。总之,这些数据表明,PPTg前部和后部(及其相关回路)对强化学习、动机激励和反应控制的贡献不同,而这些过程在药物成瘾中被认为是功能失调的。