Neuronal networks for control of eye movement

我们目前的研究集中在控制眼球运动的基底节神经元网络上。我们已经证明，由基底节神经元携带的感觉和认知信号强烈地被预期的奖励所改变。然后，这些信号被传输到名为上丘(SC)的中脑结构。SC是感觉运动转化的关键结构。包含在感觉信号中的空间信息被转换为眼睛和头部的定向运动。感觉运动转换是竞争性的，因为输入的感觉信号丰富而复杂，而定向动作是一次进行一个动作。因此，成功的行为需要一个有效的选择机制。先前与奖励相关的对象或位置更有可能被选择，因此动物更有可能定向到该对象的位置。然而，SC是否以及如何参与基于奖励的选择一直是未知的。为了回答这个问题，我们从猴子SC的单细胞活动中记录了受试者(猕猴)在非对称奖励计划下执行记忆引导的眼跳任务时的活动。 在记忆引导的眼跳任务中，视觉线索刺激表明了即将到来的眼跳的目标。它还表示，扫视后是否会给予奖励。许多SC神经元对视觉提示有反应。我们发现，当视觉提示指示即将到来的奖励时，视觉反应经常会增加。这种增加以两种不同的方式发生：1)当刺激预示着即将到来的奖励时，反应性地作为视觉反应的增加；2)当预期奖励出现在神经元的S反应场时，作为预期性活动的增加。这些效应主要在更深层的与眼跳相关的SC神经元中观察到，该神经元将接受来自皮质眼场和基底节的输入。研究结果表明，顾客满意度在定向行为的奖赏选择中起着重要作用。这些结果表明，SC神经元的奖赏选择主要来源于基底节。我们课题组以前的研究表明，在同一任务中，基底节-尾状核(CD)和黑质网状部(SNR)-的神经元表现出提示前的预期活动变化。我们以前已经证明，眼跳是由CD到SNR以及从SNR到SC的一系列抑制性连接控制的。Cd神经元的线索前活动将抑制SNR神经元的快速放电，从而使SC神经元从SNR的紧张性抑制中释放出来。我们对SC神经元的偏向效应的证明提供了基底节神经元活动和眼球运动之间的关键缺失环节。这种神经-行为关系可以作为研究基底节疾病病理机制的一个很好的系统。它还为包括帕金森病在内的基底节区疾病的诊断和治疗提供了巨大的潜力。

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. The signals are then transmitted to a midbrain structure called the superior colliculus (SC). The SC is a key structure for sensorimotor transformation. Spatial information contained in sensory signals is converted into orienting movements of the eyes and the head. The sensorimotor conversion is competitive because incoming sensory signals are abundant and complex while orienting movements are made one at a time. Successful behavior, then, requires an efficient selection mechanism. An object or position that was previously associated with reward is more likely to be selected, and consequently the animal is more likely to orient to the position of the object. However, it has been unknown whether and how the SC is involved in the reward-based selection. To answer this question, we recorded from single cell activity from the monkey SC while the subjects (macaque monkeys) performed a memory-guided saccade task with an asymmetric reward schedule. In the memory-guided saccade task, a visual cue stimulus indicated the goal of an upcoming saccade. It also indicated whether or not reward would be given after the saccade. Many SC neurons responded to the visual cue. We found that the visual responses frequently increased when the visual cue indicated an upcoming reward. The increase occurred in two distinct manners: 1) reactively as an increase in the gain of the visual response when the stimulus indicated an upcoming reward; 2) proactively as an increase in anticipatory activity when reward was expected in the neuron?s response field. These effects were observed mostly in saccade-related SC neurons in the deeper layer which would receive inputs from the cortical eye fields and the basal ganglia. We concluded that the SC plays an important role in the reward-based selection of orienting behavior. These results suggest that the reward-based selection in SC neurons is derived mainly from the basal ganglia. Previous studies from our research group showed that neurons in the basal ganglia - caudate nucleus (CD) and the substantia nigra pars reticulata (SNr) - exhibit pre-cue anticipatory changes in activity in the same task. We have shown previously that saccades are controlled by the serial inhibitory connections from the CD to the SNr and from the SNr to the SC. The pre-cue activity in CD neurons would inhibit the rapid firing of SNr neurons, and therefore SC neurons would be released from the tonic inhibition by the SNr. Our demonstration of the bias effect in SC neurons supplies the crucial missing link between the neuronal activity in the basal ganglia and eye movements. This neuron-behavior relation can be used as an excellent system in which pathological mechanism of basal ganglia diseases can be studied. It also provides a significant potential for diagnosis and treatment of basal ganglia diseases, including Parkinson's disease.