NEURAL SUBSTRATE OF LEARNING

大脑如何使人能够在奖励反馈的基础上学习新的行为，这是神经科学面临的最大挑战之一。近几十年来的研究已经产生了大量关于控制行为肌肉方面的神经回路以及参与积极刺激感知的大脑结构的知识，但奖赏回路在大脑中作用于运动控制回路以改变未来行为的位置仍然是一个谜。这个项目的目的是分析大脑中奖赏回路和相对为人所知的运动回路汇合的部分的连接，以确定它在学习新行为中的作用。猴子将被教导执行简单的行为，即在视频屏幕上25个可能的点中的两个目标点之间来回移动眼睛。他们将获得直接的大脑刺激，因为这是一个耗时的过程，即找到正确的目标并在两者之间交替凝视。这项研究的目标是：(1)确定大脑中刺激足够奖励的特定区域，使动物学会寻找新目标并在新目标之间切换凝视；(2)确定通过这些区域到达额叶皮质中已知神经细胞在学习眼球运动期间活跃的特定神经路径；以及(3)确定用暂时扰乱其功能的神经化学制剂治疗该区域是否会阻止学习对新目标的眼动。两只动物接受了颅骨植入，其中一只接受了充分的测试，证明了当对丘脑内侧背侧核进行电刺激时，它会迅速学会眼球运动。

The question of how the brain enables one to learn new behavior on the basis of rewarding feedback is one of neuroscience's greatest challenges. Research in recent decades has produced considerable knowledge about the neurocircuitry that controls the muscular aspect of behavior and about brain structures that are involved in the perception of positive stimulation, but the location of a site in the brain where a reward circuit acts on a motor control circuit to change future behavior remains an enigma. The purpose of this project is to analyze the connections of a part of the brain where a reward circuit and a relatively well-understood motor circuit converge to determine its role in the learning of new behaviors. Monkeys will be taught to perform the simple behavior of moving the eyes back and forth between two target spots out of 25 possible spots on a video screen. They will be rewarded with direct brain stimulation for the time-consuming process of finding the correct pair of targets and gazing alternately between the two. The goals of the research are to (1) identify the specific areas in the brain where stimulation is sufficiently rewarding that the animal learns to find and alternate gaze between new targets; (2) identify the specific nerve pathways that pass through those areas to an area in frontal cortex where nerve cells are known to be active during the learning of eye movements; and (3) determine whether treatment of that area with neurochemical agents that temporarily disrupt its function prevents the learning of eye movements to new targets. Two animals have received cranial implants and one was tested sufficiently to demonstrate that it learned rapidly to make eye movements when rewarded by electrical stimulation of the medial dorsal nucleus of the thalamus.