Neuronal networks for control of eye movement

我们目前的研究主要集中在控制眼球运动的基底神经节神经元网络。我们已经证明，基底神经节神经元携带的感觉和认知信号会受到预期奖励的强烈影响。我们假设奖赏依赖性调制发生在基底神经节内。具体地说，从大脑皮质区到尾状核（CD）的兴奋性输入（携带空间信号）受到来自中脑多巴胺（DA）神经元的输入的调制。为了检验这个模型，我们进行了如下所示的两种实验。 DA拮抗剂注射：一个被称为基底神经节的大脑区域被认为包含控制身体运动自发启动的神经元（神经细胞）。在这里，我们展示了基底神经节中一种叫做多巴胺的神经递质的正常释放，它是将眼睛定向到奖励的东西所必需的。我们注射了少量药物，阻止多巴胺与尾状核（基底神经节的一部分）神经元上的受体结合，同时动物将眼睛对准与大奖励相关的光点或与小奖励相关的另一个点。一种药物，称为D1拮抗剂，减缓眼球运动到一个大的奖励相关点，而另一种药物，称为D2拮抗剂，减缓眼球运动到一个小的奖励相关点。我们的研究表明，复杂的神经回路，作为一个运动控制器，是由一种特定的化学物质，多巴胺微调，以实现对生存至关重要的目标。 基底神经节和大脑额叶皮层之间的比较：我们报告说，在皮层和基底神经节，两个控制运动生成的高阶区域，单个神经元活动反映了对更大奖励的偏好。在使用眼睛运动的非人灵长类动物模型系统中，通常假设前眼场（皮层区域）指定运动度量（例如，方向，幅度），而基底神经节提供激励信息（例如，一个动作是否会导致奖励）。在这里，我们表明，使用相同的猴子在相同的任务，预期奖励调制单个神经元活动在额叶眼场和基底神经节，如果这种活动也进行运动相关的信息。这些结果提出了一种可能性，即皮层也可能对奖励调制行为提供动机信息。进一步阐明大脑皮层中动机信息的来源和功能可能会导致识别新的神经靶点，用于补偿基底神经节功能受损患者的动机相关缺陷。

Our current research is focused on the neuronal networks in the basal ganglia which control eye movements. We have shown that sensory and cognitive signals carried by neurons in the basal ganglia are strongly modified by expected reward. We hypothesized that the reward-dependent modulation occurs within the basal ganglia. Specifically, excitatory inputs from the cerebral cortical areas to the caudate nucleus (CD), which carry spatial signals, are modulated by inputs from midbrain dopamine (DA) neurons. To test this model, we conducted two kinds of experiments as shown below. DA antagonist injections: A brain area called the basal ganglia is known to contain neurons (nerve cells) that control voluntary initiation of body movements. Here we show that the normal release of a neurotransmitter, called dopamine, in the basal ganglia is necessary for orienting eyes to something rewarding. We injected a small amount of drugs that prevent dopamine from binding to its receptors on neurons in the caudate nucleus, part of the basal ganglia, while animals were orienting their eyes to a light spot associated with a large reward or to another spot associated with a small reward. One drug, called D1 antagonist, slowed eye movements to a large reward-associated spot, while another drug, called D2 antagonist, slowed eye movements to a small reward-associated spot. Our study demonstrates that complex neural circuits, acting as a movement controller, are fine-tuned by a specific chemical substance, dopamine, to achieve goals that are critical for survival. Comparison between the basal ganglia and the cerebral frontal cortex: We report that single neuron activity in the cortex and basal ganglia, two higher-order areas controlling movement generation, reflects preference for larger reward. In the non-human primate model system using eye movement, it has been generally assumed that the frontal eye field (a cortical area) specifies movement metrics (e.g., direction, amplitude), while the basal ganglia provides motivational information (e.g., whether a movement will result in reward). Here we show that, using the same monkeys in the same task, expected reward modulates single neuron activity in both the frontal eye field and basal ganglia, if such activity also carries movement metrics-related information. These results raise the possibility that cortex may also contribute motivational information to reward modulated behaviors. Further elucidation of the origin and function of the motivation information in the cortex might lead to identification of new neural targets for compensating motivation-related deficits in patients with compromised basal ganglia functions.