International Research Fellowship Program: Computional Roles of Acetylcholine in Attention and Associative Learning

[603098]国际研究奖学金计划使美国科学家和工程师能够在国外进行9至24个月的研究。该计划的奖励为联合研究提供了机会，并利用独特或互补的设施、专业知识和国外的实验条件。该奖项将支持Christopher a. Cordova博士与加拿大麦吉尔大学的Barbara Jones博士进行为期24个月的研究。大脑辨别环境因果结构的能力来自于注意力的适当分配和对刺激之间预测关系的联想学习。基底前脑的胆碱能神经元对外围皮层的神经活动和可塑性具有深远的影响，并可能在生物重大事件的选择性加工中发挥重要作用。最近的行为研究表明，胆碱能神经元增加对预测线索的处理，与正在进行的刺激预测的不确定性成比例，这一策略与贝叶斯学习模型非常相似，该模型在累积刺激历史的基础上调节统计上最优关联的发展。利用神经元记录、神经化学标记和行为技术的新组合，正在进行一系列研究，以评估基底前脑胆碱能系统在调节皮层的注意力和学习过程中的作用。一项研究通过记录和标记大鼠基底前脑的神经元，描述了胆碱能神经元在学习线索和液体奖励之间的概率关系时的调节作用。因此，通过将细胞化学鉴定的胆碱能神经元的活性与不同学习阶段奖励预测的假设不确定性联系起来，可以评估胆碱能神经元的计算作用。具有奖励和厌恶味觉结果的任务的变化评估了胆碱能神经元在相同的预测不确定性假设测量下调节不同效价类别条件刺激加工的可能性。另一项研究通过记录和标记相同行为任务中下丘脑外侧的食欲素神经元，评估了一个主要输入结构对胆碱能系统的贡献。食欲素神经元有助于调节食物驱动，并在高度觉醒状态下维持大脑的稳定清醒状态中发挥关键作用。因此，食欲素神经元的活动可能反映了线索呈现后预期的奖励，也可以预测厌恶的结果，反映了在预期生物学重要事件时皮质活动的调节作用。尽管胆碱能神经元和食欲素神经元具有重要的调节作用，但它们在行为任务中都没有被记录下来。在相对简单的学习任务中使用这些技术，将允许对调节大脑皮层清醒、专注和学习状态的神经生物学过程的强大但未经检验的假设进行评估。

0603098CordovaThe International Research Fellowship Program enables U.S. scientists and engineers to conduct nine to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad.This award will support a twenty-four-month research fellowship by Dr. Christopher A. Cordova to work with Dr. Barbara Jones at McGill University in Canada.The brain's ability to discern the causal fabric of the environment arises from the appropriate allocation of attention and associative learning to predictive relations between stimuli. Cholinergic neurons in the basal forebrain exert a profound influence on neural activity and plasticity in the outlying cortex, and may play an important role in the selective processing of biologically significant events. Recent behavioral studies have suggested that cholinergic neurons increase the processing of predictive cues in proportion to the uncertainty of ongoing stimulus predictions, a strategy that is closely analogous to that of Bayesian models of learning that regulate the development of statistically optimal associations on the basis of a cumulative stimulus history. Using a novel combination of neuron recording, neurochemical labeling and behavioral techniques, a series of studies are being conducted to assess the role of the basal forebrain cholinergic system in regulating attention and learning processes in the cortex. One study characterizes the modulatory role of cholinergic neurons by recording and labeling neurons in the basal forebrain of rats while they learn probabilistic relations between cues and liquid rewards. The computational role of cholinergic neurons can thereby be assessed by relating the activity of cytochemically identified cholinergic neurons to the hypothesized uncertainty of reward predictions across different stages of learning. A variation of the task with both rewarding and aversive gustatory outcomes assesses the possibility that cholinergic neurons regulate the processing of conditioned stimuli with different valence classes with the same hypothesized measure of predictive uncertainty. Another study assesses the contributions of a major input structure to the cholinergic system by recording and labeling orexin neurons in the lateral hypothalamus during the same behavioral tasks. Orexin neurons contribute to the mediation of food drives, and play a critical role in maintaining the stable wakefulness of the brain during states of heightened arousal. The activity of orexin neurons may thus reflect anticipated rewards following the presentation of cues and could also predict aversive outcomes, reflecting a role in the regulation of cortical activity in anticipation of biologically important events. Despite their prominent regulatory roles, neither cholinergic nor orexin neurons have been recorded during a behavioral task. The use of these techniques in relatively simple learning tasks will allow an evaluation of powerful, yet untested hypotheses of neurobiological processes that regulate the waking, attentive and learning states of the cortex.