Quintana-Feliciano Richard, Gobin Christina, Kane Louisa, Sortman Bo, Rakela Samantha, Genovese Ariana, Tunstall Brendan, Caprioli Daniele, Iñiguez Sergio D, Warren Brandon L
Department of Pharmacodynamics, University of Florida, Gainesville, FL 32610.
Behavioral Neuroscience Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health/Department of Health and Human Services, Baltimore, MD 21224.
eNeuro. 2021 Apr 23;8(2). doi: 10.1523/ENEURO.0373-20.2021. Print 2021 Mar-Apr.
Neuronal ensembles in the infralimbic cortex (IL) develop after prolonged food self-administration training. However, rats demonstrate evidence of learning the food self-administration response as early as day 1, with responding quickly increasing to asymptotic levels. Since the contribution of individual brain regions to task performance shifts over the course of training, it remains unclear whether IL ensembles are gradually formed and refined over the course of extensive operant training, or whether functionally-relevant ensembles might be recruited and formed as early as the initial acquisition of food self-administration behavior. Here, we aimed to determine the role of IL ensembles at the earliest possible point after demonstrable learning of a response-outcome association. We first allowed rats to lever press for palatable food pellets and stopped training rats once their behavior evidenced the response-outcome association (learners). We compared their food-seeking behavior and neuronal activation (Fos protein expression) to similarly trained rats that did not form this association (non-learners). Learners had greater food-seeking behavior and neuronal activation within the medial prefrontal cortex (mPFC), suggesting that mPFC subregions might encode initial food self-administration memories. To test the functional relevance of mPFC Fos-expressing ensembles to subsequent food seeking, we tested region-wide inactivation of the IL using muscimol+baclofen and neuronal ensemble-specific ablation using the Daun02 inactivation procedure. Both region-wide inactivation and ensemble-specific inactivation of the IL significantly decreased food seeking. These data suggest that IL neuronal ensembles form during initial learning of food self-administration behavior, and furthermore, that these ensembles play a functional role in food seeking.
在长时间的食物自我给药训练后，眶下皮质（IL）中的神经元集群得以发育。然而，早在训练第1天，大鼠就已表现出学习食物自我给药反应的迹象，其反应迅速增加至渐近水平。由于在训练过程中，各个脑区对任务表现的贡献会发生变化，因此目前尚不清楚IL神经元集群是在广泛的操作性训练过程中逐渐形成并完善的，还是在最初获得食物自我给药行为时就可能招募并形成了功能相关的集群。在这里，我们旨在确定在可证明学习到反应-结果关联后的最早时间点，IL神经元集群所起的作用。我们首先让大鼠按压杠杆以获取美味的食物颗粒，一旦它们的行为证明了反应-结果关联，就停止训练这些大鼠（学习者）。我们将它们的觅食行为和神经元激活（Fos蛋白表达）与未形成这种关联的类似训练大鼠（非学习者）进行比较。学习者在内侧前额叶皮质（mPFC）内具有更强的觅食行为和神经元激活，这表明mPFC亚区可能编码了最初的食物自我给药记忆。为了测试mPFC中表达Fos的神经元集群与后续觅食的功能相关性，我们使用蝇蕈醇+巴氯芬测试了IL的全区域失活，并使用道诺霉素02失活程序测试了神经元集群特异性消融。IL的全区域失活和集群特异性失活均显著降低了觅食行为。这些数据表明，IL神经元集群在食物自我给药行为的初始学习过程中形成，而且这些集群在觅食中发挥着功能作用。
