Neuronal networks for control of eye movement

纹状体通过两种方式控制行为：促进和抑制，分别通过直接和间接途径。然而，目前还不清楚在这些途径中处理的是什么信息。为了解决这个问题，我们研究了两条起源于灵长类尾部(CDT)的通路。我们发现CDT直接或间接地通过苍白球外球尾腹侧支配黑质网状部的尾侧-背外侧部。值得注意的是，从CDT接受输入的cvGPe神经元大多是视觉神经元，根据长期的经验编码视觉对象的稳定奖励值。它们的主要反应是被无价值的物体抑制，这产生了对cdlSNr神经元的去抑制和对上丘神经元的抑制。我们的数据表明，低值信号是通过CDT-间接途径发送的，以抑制对无价值物体的扫视，而高价值信号是通过CDT-直接途径发送的，以促进对有价值物体的扫视。 我们在发现目标后立即达到目标，或者稍后通过暂缓立即行动来达到目标。每一次，我们都会通过压制其中一个动作来选择另一个动作。大脑是如何控制这些对抗行为的？我们假设，基底节(BG)的输出黑质网状结构(SNR)通过向上丘(SC)发送强烈的抑制性输出来抑制拮抗的动眼神经信号。为了验证这一假设，我们训练猴子执行两种眼跳任务：即刻(视觉引导)和延迟(视觉抑制，但记忆引导)。在这两个任务中，我们使用单向奖赏(1DR)程序来修正目标达成动机水平。我们通过逆行激活SC来鉴定投射到SC的SNR神经元。我们刺激两侧SC是因为投射到同侧SC的SNR神经元(IpsiSC)和投射到对侧SC的SNR神经元可能具有拮抗作用。首先，我们发现ipsiSC投射神经元大约是对照SC投射神经元的10倍。更重要的是，ipsiSC投射SNR神经元大致分为两组，分别控制即刻和延迟的眼跳。在视觉和记忆1DR任务中，对侧的视觉靶点均明显抑制即时型SNR神经元。这种抑制将解除对SC神经元的抑制，并促进对侧靶点的扫视。这在VISUAL-1DR任务中是目标导向的，但在Memory-1DR任务中是错误的。相反，延迟型SNR神经元倾向于被视觉目标(尤其是对侧)兴奋，这将抑制对目标的即时扫视。相反，在延迟的(记忆引导的)指向对侧的扫视之前，它们被抑制，这将促进扫视。对照SC投射的SNR神经元更加多变，没有分组的特征，尽管它们中的一些可能参与了对同侧靶点的扫视。最后，我们发现一些ipsiSC投射的SNR神经元在期望获得奖励时受到更强烈的抑制，这与缩短的扫视反应时间有关。然而，许多SNR神经元没有表现出奖赏-期望效应。这些结果表明，BG中存在两个独立的动眼神经回路，它们都有助于目标定向行为，但在不同的时间背景下。 基底节主要根据它们的值来控制身体的运动。这种机制的关键是多巴胺神经元，它主要向纹状体发送不可预测的值信号。这种机制使动物能够灵活地改变自己的行为，最终选择有价值的行为。然而，这可能不是最好的行为，因为灵活的选择集中在最近的，因此，有限的经验(即，短期记忆)。我们以前和最近的研究表明，基底节包含以完全不同的方式处理价值信号的独立电路。他们对最近的价值变化不敏感，但逐渐积累了每一种行为的价值(即运动或对象选择)。这些稳定的电路最终对许多行为的值进行编码，然后将值信号保留很长时间(即长期记忆)。它们受到一组单独的多巴胺神经元的支配，即使在没有预测到奖励的情况下，这些神经元也会保留价值信号。重要的是，稳定的回路可以快速而准确地控制运动行为(例如手或眼睛)，这使得动物可以根据历史生活经验自动获得有价值的结果。这些行为将被称为技能，这对生存至关重要。稳定环路位于基底神经节的后部，与位于前部的柔性环路分开。总而言之，基底神经节中灵活而稳定的回路，共同工作但又独立工作，使动物(和人类)能够在不同的背景下实现有价值的目标。

The striatum controls behavior in two ways: facilitation and suppression through the direct and indirect pathways, respectively. However, it is still unclear what information is processed in these pathways. To address this question, we studied two pathways originating from the primate caudate tail (CDt). We found that the CDt innervated the caudal-dorsallateral part of the substantia nigra pars reticulata (cdlSNr), directly or indirectly through the caudalventral part of the globus pallidus externus (cvGPe). Notably, cvGPe neurons receiving inputs from the CDt were mostly visual neurons that encoded stable reward values of visual objects based on long-past experiences. Their dominant response was inhibition by valueless objects, which generated disinhibition of cdlSNr neurons and inhibition of superior colliculus neurons. Our data suggest that low-value signals are sent by the CDt-indirect pathway to suppress saccades to valueless objects, whereas high-value signals are sent by the CDt-direct pathway to facilitate saccades to valuable objects. We reach a goal immediately after detecting the target, or later by withholding the immediate action. Each time, we choose one of these actions by suppressing the other. How does the brain control these antagonistic actions? We hypothesized that the output of basal ganglia (BG), substantia nigra pars reticulata (SNr), suppresses antagonistic oculomotor signals by sending strong inhibitory output to superior colliculus (SC). To test this hypothesis, we trained monkeys to perform two kinds of saccade task: Immediate (visually guided) and delayed (visually-withheld but memory-guided) saccade tasks. In both tasks, we applied one-direction-reward (1DR) procedure to modify the level of goal-reaching motivation. We identified SNr neurons that projected to SC by their antidromic activation from SC. We stimulated SC on both sides because SNr neurons projecting to the ipsilateral SC (ipsiSC) and those projecting to the contralateral SC (contraSC) might have antagonistic functions. First, we found that ipsiSC-projecting neurons were about 10 times more than contraSC-projecting neurons. More importantly, ipsiSC-projecting SNr neurons were roughly divided into two groups which would control immediate and delayed saccades separately. The immediate-type SNr neurons were clearly inhibited by a visual target on the contralateral side in both visual- and memory-1DR tasks. The inhibition would disinhibit SC neurons and facilitate a saccade to the contralateral target. This is goal-directed in visual-1DR task, but is erroneous in memory-1DR task. In contrast, the delayed-type SNr neurons tended to be excited by a visual target (especially on the contralateral side), which would suppress the immediate saccade to the target. Instead, they were inhibited before a delayed (memory-guided) saccade directed to the contralateral side, which would facilitate the saccade. ContraSC-projecting SNr neurons were more variable with no grouped features, although some of them may contribute to the saccade to the ipsilateral target. Finally, we found that some ipsiSC-projecting SNr neurons were inhibited more strongly when reward was expected, which was associated with shortened saccade reaction times. However, many SNr neurons showed no reward-expectation effect. These results suggest that two separate oculomotor circuits exist in BG, both of which contribute to goal-directed behavior, but in different temporal contexts. The basal ganglia control body movements, mainly, based on their values. Critical for this mechanism is dopamine neurons, which sends unpredicted value signals, mainly, to the striatum. This mechanism enables animals to change their behaviors flexibly, eventually choosing a valuable behavior. However, this may not be the best behavior, because the flexible choice is focused on recent, and, therefore, limited, experiences (i.e., short-term memories). Our old and recent studies suggest that the basal ganglia contain separate circuits that process value signals in a completely different manner. They are insensitive to recent changes in value, yet gradually accumulate the value of each behavior (i.e., movement or object choice). These stable circuits eventually encode values of many behaviors and then retain the value signals for a long time (i.e., long-term memories). They are innervated by a separate group of dopamine neurons that retain value signals, even when no reward is predicted. Importantly, the stable circuits can control motor behaviors (e.g., hand or eye) quickly and precisely, which allows animals to automatically acquire valuable outcomes based on historical life experiences. These behaviors would be called skills, which are crucial for survival. The stable circuits are localized in the posterior part of the basal ganglia, separately from the flexible circuits located in the anterior part. To summarize, the flexible and stable circuits in the basal ganglia, working together but independently, enable animals (and humans) to reach valuable goals in various contexts.