Losing Control: Excessive Alcohol Seeking after Selective Inactivation of Cue-Responsive Neurons in the Infralimbic Cortex
Losing Control: Excessive Alcohol Seeking after Selective Inactivation of Cue-Responsive Neurons in the Infralimbic Cortex
复制标题
DOI：
10.1523/jneurosci.0684-15.2015
复制
发表时间：
2015-07-29
影响因子：
5.3
通讯作者：
Sommer, Wolfgang H.
中科院分区：
文献类型：
--
作者：
Pfarr, Simone;Meinhardt, Marcus W.;Sommer, Wolfgang H.
饮酒失控是酒精中毒的一个关键缺陷，与内侧前额叶皮质（mPFC）功能障碍有因果关系，但潜在的分子和细胞机制仍不清楚。线索诱导的酒精寻求的恢复激活了大鼠mPFC神经元的一个子集，通过其共同表达的活动标记cFos和包括主神经元和中间神经元来识别。在这里，我们分别使用cFos-lacZ和pCAG-lacZ转基因大鼠进行神经元的活性依赖性或非选择性失活，其通过其lacZ编码的β-半乳糖苷酶活性将失活的前药Daun02转化为神经毒素柔红霉素。我们报告说，活动依赖性消融的神经元合奏在边缘下，而不是边缘前亚区诱导过度酒精寻求。靶向神经元系综是特定的线索诱导的反应，因为应力诱导的恢复在这些动物中不受影响。重要的是，使用pCAG-lacZ大鼠非选择性失活的边缘下神经元，没有功能的后果线索诱导的恢复任务。因此，抑制控制酒精寻求是由不同的功能合奏在边缘下皮层，而不是由一般的抑制音，这一地区的行为输出。这表明大鼠mPFC内存在高水平的功能区室化，许多功能集合体可以在同一子区域内共存并相互作用。
Loss of control over drinking is a key deficit in alcoholism causally associated with malfunction of the medial prefrontal cortex (mPFC), but underlying molecular and cellular mechanisms remain unclear. Cue-induced reinstatement of alcohol seeking activates a subset of mPFC neurons in rats, identified by their common expression of the activity marker cFos and comprised of both principal and interneurons. Here, we used cFos-lacZ and pCAG-lacZ transgenic rats for activity-dependent or nonselective inactivation of neurons, respectively, which by their lacZ encoded beta-galactosidase activity convert the inactive prodrug Daun02 into the neurotoxin daunorubicin. We report that activity-dependent ablation of a neuronal ensemble in the infralimbic but not the prelimbic subregion induced excessive alcohol seeking. The targeted neuronal ensemble was specific for the cue-induced response because stress-induced reinstatement was not affected in these animals. Importantly, nonselective inactivation of infralimbic neurons, using pCAG-lacZ rats, was without functional consequence on the cue-induced reinstatement task. Thus, inhibitory control over alcohol seeking is exerted by distinct functional ensembles within the infralimbic cortex rather thanbya general inhibitory tone of this regiononthe behavioral output. This indicates a high level of functionalcompartmentation within the rat mPFC whereat many functional ensembles could coexist and interact within the same subregion.