Ernest Gallo Clinic and Research Center, Department of Neurology, Wheeler Center for the Neurobiology of Addiction, University of California at San Francisco, San Francisco, California 94143.
J Neurosci. 2013 Oct 2;33(40):15989-98. doi: 10.1523/JNEUROSCI.0026-13.2013.
Animals rely on environmental cues to identify potential rewards and select the best reward available. The orbitofrontal cortex (OFC) is proposed to encode sensory-specific representations of expected outcome. However, its contribution to the selection of a preferred outcome among different reward options is still unclear. We investigated the effect of transient OFC inactivation (achieved by presession injection of muscimol and baclofen) in a novel two-reward choice task. In discrete trials, rats could choose between a solution of polycose and an equally caloric, but highly preferred, solution of sucrose by visiting one of two liquid dispensers after the presentation of a specific cue signaling the availability of one or both of the solutions. We found that OFC inactivation did not affect outcome preference: rats maintained high preference for sucrose and adapted their behavioral responding when the cue-outcome contingencies were reversed. However, when rats were tested drug-free 24 h after OFC inactivation and reversal learning, memory for the newly learned contingencies was poor. These results suggest a potential conflict between OFC (encoding pre-reversal contingencies) and other brain circuits (encoding the new contingencies). Remarkably, repeating the OFC inactivation before the reversal memory test restored normal behavior, confirming the hypothesis of a dominant impact of OFC on other decision-making circuits. These results indicate that the representations encoded in the OFC, while not essential to the expression of outcome preference, exert hierarchical control on downstream decision-making circuits.
动物依赖环境线索来识别潜在的奖励,并选择最佳的可用奖励。眶额皮层(OFC)被认为编码预期结果的感觉特异性表示。然而,其在不同奖励选项中选择首选结果的贡献尚不清楚。我们在一项新的双奖励选择任务中研究了瞬态 OFC 失活(通过预 session 注射 muscimol 和 baclofen 实现)的影响。在离散试验中,大鼠可以通过访问两个液体分配器之一来选择多聚糖溶液和等热量但高度偏好的蔗糖溶液,前提是特定线索表示可用的一个或两个解决方案之一。我们发现 OFC 失活不会影响结果偏好:大鼠保持对蔗糖的高度偏好,并在线索-结果关联被反转时适应其行为反应。然而,当大鼠在 OFC 失活和反转学习 24 小时后无药物测试时,对新学习的关联的记忆很差。这些结果表明 OFC(编码反转前的关联)和其他大脑回路(编码新的关联)之间存在潜在冲突。值得注意的是,在反转记忆测试之前重复 OFC 失活会恢复正常行为,证实了 OFC 对其他决策回路具有主导影响的假设。这些结果表明,OFC 中编码的表示虽然对于表达结果偏好不是必需的,但对下游决策回路施加了分层控制。