Neural Basis of Sensory Discrimination Learning

描述(由申请人提供)：申请的长期目标是完整地描述和理解当学习到感觉辨别时大脑如何变化。首席调查员领导了最近的技术进步，使皮质植入物能够在多个月的时间里采样相同大脑位置的动作电位反应。这些进展首次提供了机会来研究大脑中分布的动作电位是如何在整个学习过程中每天发生变化的。我们之前的工作在整个学习过程中对动物进行了监测。在选择目标和避免分心因素后的头两天，对任务目标和非目标的动作电位反应都增加了几倍，感受野在空间上扩大了。随着时间的推移，反应性恢复到正常水平，对任务分心因素的反应变得选择性地受到抑制。我们的工作假设是，这些可塑性效应只取决于认知奖赏关联。在第一个研究中，我们将在检测和辨别任务中连续训练植入的动物，其中目标分配保持不变，在每个任务中持续几周。本实验将分离通过将奖赏与任务目标刺激联系在一起以及将奖赏缺失与任务分心因素联系起来而产生的神经可塑性效应。然后，动物将执行相同的任务，目标任务和分心任务互换，以逆转奖励关联。然后，动物将被经典地限制在相同的刺激下，这种刺激保留了奖赏关联，同时引入了广泛的行为变化；初步数据显示，这种转变产生了最小的神经可塑性。然后，作为一个经典的条件反射实验，目标和分心奖赏的关联将被颠倒。其他研究将测试皮质可塑性的一致输入模型和奖励关联模型，以确定当它们不一致时，哪个优先。最后，研究将测试由这些关联引起的神经可塑性规则是如何由大脑的神经调节系统实施的假设。在每项研究中，将在行为表现之前和期间监测3b区的尖峰反应、局部场电位和感受场，以创建输出测量来与行为数据进行比较。 这项研究建议对基础学习中的电路进行基础科学研究。它将为未来十年公共卫生领域肯定非常活跃的领域奠定基础。这些神经调节中心的异常，如基底核、黑质和蓝斑，被认为是一系列神经和精神障碍的幕后推手，如年龄相关性认知障碍、阿尔茨海默病、帕金森病、精神分裂症、一般抑郁症、强迫症和成瘾。了解我们学习时大脑是如何变化的，将使我们能够更有针对性地研究学习，从而神经调节活动在这些神经条件下是如何异常的。然而，这是一项基础科学应用，因此对公共卫生的直接适用性将取决于后续的应用研究。

DESCRIPTION (provided by applicant): The long-term objective of the application is a complete description and understanding of how the brain changes when a sensory discrimination is learned. The Principal Investigator has led recent technological advances that let cortical implants sample action potential responses from the same brain locations over many months. These advances provide the opportunity, for the first time, to study how the distributed generation of action potentials in the brain changes on a daily basis throughout the learning process. Our prior work has monitored animals throughout the learning process. In the first two days after selecting for targets and avoiding distractors, action potential responses to both task targets and non-targets increase several-fold, and receptive fields broaden spatially. With time, responsiveness returns to normal levels, and responses to task distractors become selectively suppressed. Our working hypothesis is that these plasticity effects depend only on cognitive reward associations. In the first study we will serially train implanted animals in detection and discrimination tasks in which the target assignment is kept constant, for several weeks at each task. This experiment will separate neuroplasticity effects that occur through associating rewards with task target stimuli and associating omission of reward with task distractors. Animals will then perform the same task with target and distractor assignments swapped, to reverse reward associations. Then, animals will be classically conditioned to the same stimuli, which preserve reward associations while introducing a broad range of behavioral changes; preliminary data shows minimal neuroplasticity results from this transition. Then, as a classical conditioning experiment, target and distractor reward associations will be reversed. Other studies will test coincident-input models of cortical plasticity against reward association models to determine which takes precedence when they are inconict. And lastly, studies will test hypotheses on how the neuroplasticity rules caused by these associations are implemented by the brain's neuromodulatory systems. Throughout each study, spike responses, local field potentials, and receptive fields in area 3b will be monitored before and during behavioral performance to create output measures to compare with behavioral data. This study proposes basic science investigations into circuitry underlying learning. It will lay the substrate for what is sure to be a very active area in public health in the coming decade. Abnormalities in these neuromodulatory centers, the Nucleus Basalis, Substantia Nigra, and Locus Coeruleus, are thought to be behind an array of neurological and mental disorders such as age-related cognitive decline, Alzheimer's disease, Parkinson's disease, Schizophrenia, General Depression, OCD, and addiction. Understanding how the brain changes when we learn will enable more targeted studies of how learning, and thus neuromodulatory activity, is abnormal in these neurological conditions. However, this is a basic science application, and so direct applicability to public health will depend upon follow-up applied studies.