Eddy Meghan C, Todd Travis P, Bouton Mark E, Green John T
University of Vermont, Department of Psychological Science, 2 Colchester Ave., Burlington, VT 05405, United States.
University of Vermont, Department of Psychological Science, 2 Colchester Ave., Burlington, VT 05405, United States.
Neurobiol Learn Mem. 2016 Feb;128:33-9. doi: 10.1016/j.nlm.2015.12.003. Epub 2015 Dec 23.
Instrumental renewal, the return of extinguished instrumental responding after removal from the extinction context, is an important model of behavioral relapse that is poorly understood at the neural level. In two experiments, we examined the role of the dorsomedial prefrontal cortex (dmPFC) and the ventromedial prefrontal cortex (vmPFC) in extinction and ABA renewal of instrumental responding for a sucrose reinforcer. Previous work, exclusively using drug reinforcers, has suggested that the roles of the dmPFC and vmPFC in expression of extinction and ABA renewal may depend at least in part on the type of drug reinforcer used. The current experiments used a food reinforcer because the behavioral mechanisms underlying the extinction and renewal of instrumental responding are especially well worked out in this paradigm. After instrumental conditioning in context A and extinction in context B, we inactivated dmPFC, vmPFC, or a more ventral medial prefrontal cortex region by infusing baclofen/muscimol (B/M) just prior to testing in both contexts. In rats with inactivated dmPFC, ABA renewal was still present (i.e., responding increased when returned to context A); however responding was lower (less renewal) than controls. Inactivation of vmPFC increased responding in context B (the extinction context) and decreased responding in context A, indicating no renewal in these animals. There was no effect of B/M infusion on rats with cannula placements ventral to the vmPFC. Fluorophore-conjugated muscimol was infused in a subset of rats following test to visualize infusion spread. Imaging suggested that the infusion spread was minimal and mainly constrained to the targeted area. Together, these experiments suggest that there is a region of medial prefrontal cortex encompassing both dmPFC and vmPFC that is important for ABA renewal of extinguished instrumental responding for a food reinforcer. In addition, vmPFC, but not dmPFC, is important for expression of extinction of responding for a food reinforcer. The role of the medial prefrontal cortex in renewal in the original conditioning context may depend in part on control over excitatory context-response or context-(response-outcome) relations that might be learned in acquisition. The role of the vmPFC in expression of extinction may depend on its control over inhibitory context-response or context-(response-outcome) relations that are learned in extinction.
工具性恢复,即从消退环境移除后消退的工具性反应的恢复,是行为复发的一个重要模型,但其在神经层面的理解尚浅。在两项实验中,我们研究了背内侧前额叶皮层(dmPFC)和腹内侧前额叶皮层(vmPFC)在蔗糖强化物的工具性反应消退及ABA恢复中的作用。以往的研究仅使用药物强化物,表明dmPFC和vmPFC在消退表达及ABA恢复中的作用可能至少部分取决于所使用的药物强化物类型。当前实验使用食物强化物,因为在这一范式中,工具性反应消退和恢复背后的行为机制已得到充分研究。在情境A中进行工具性条件训练并在情境B中消退后,我们在两个情境测试前通过注入巴氯芬/蝇蕈醇(B/M)使dmPFC、vmPFC或更腹侧的内侧前额叶皮层区域失活。在dmPFC失活的大鼠中,ABA恢复仍然存在(即回到情境A时反应增加);然而,反应比对照组更低(恢复较少)。vmPFC失活增加了情境B(消退情境)中的反应,并减少了情境A中的反应,表明这些动物没有恢复。向vmPFC腹侧插管的大鼠注入B/M没有效果。测试后,向一部分大鼠注入荧光团偶联的蝇蕈醇以观察注入扩散情况。成像显示注入扩散最小,主要局限于目标区域。总之,这些实验表明,内侧前额叶皮层中一个同时包含dmPFC和vmPFC的区域对于食物强化物的消退工具性反应的ABA恢复很重要。此外,vmPFC而非dmPFC对于食物强化物反应消退的表达很重要。内侧前额叶皮层在原始条件训练情境中的恢复作用可能部分取决于对兴奋性情境 - 反应或情境 - (反应 - 结果)关系的控制,这些关系可能在习得过程中被学习到。vmPFC在消退表达中的作用可能取决于其对在消退过程中学习到的抑制性情境 - 反应或情境 - (反应 - 结果)关系的控制。