Neural Basis of Sensory Discrimination Learning

描述（由申请人提供）：该申请的长期目标是完整描述和理解学习感觉辨别时大脑如何变化。首席研究员领导了最新的技术进步，使皮层植入物可以在数月内对同一大脑位置的动作电位反应进行采样。这些进展首次为研究大脑中动作电位的分布式生成在整个学习过程中每天如何变化提供了机会。我们之前的工作是在整个学习过程中监控动物。在选择目标并避免干扰因素后的前两天，对任务目标和非目标的动作电位反应增加了数倍，并且感受野在空间上扩大。随着时间的推移，反应能力恢复到正常水平，并且对任务干扰的反应被选择性地抑制。我们的工作假设是，这些可塑性效应仅取决于认知奖励关联。在第一项研究中，我们将连续训练植入的动物进行检测和辨别任务，其中目标分配保持不变，每次任务持续数周。该实验将通过将奖励与任务目标刺激相关联以及将奖励的省略与任务干扰因素相关联而发生神经可塑性效应。然后，动物将执行相同的任务，交换目标和干扰任务，以逆转奖励关联。然后，动物将传统地适应相同的刺激，从而保留奖励关联，同时引入广泛的行为变化；初步数据显示，这种转变产生的神经可塑性极小。然后，作为经典的条件反射实验，目标​​和干扰奖励关联将被颠倒。其他研究将测试皮质可塑性的一致输入模型与奖励关联模型，以确定当它们不一致时哪个优先。最后，研究将测试有关大脑神经调节系统如何实施这些关联引起的神经可塑性规则的假设。在每项研究中，将在行为表现之前和行为期间监测尖峰反应、局部场电位和区域 3b 中的感受野，以创建输出测量以与行为数据进行比较。 这项研究提出了对学习背后的电路进行基础科学调查。它将为未来十年必将成为公共卫生领域非常活跃的领域奠定基础。这些神经调节中心（基底核、黑质和蓝斑）的异常被认为是一系列神经和精神疾病的背后原因，例如与年龄相关的认知能力下降、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。了解学习时大脑如何变化将有助于更有针对性地研究学习以及神经调节活动在这些神经系统疾病中是如何异常的。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.