Neuronal networks for control of eye movement

选择有价值的物品对生存至关重要，但它们的价值可能会灵活变化或保持稳定。因此，动物应该能够通过最近的经验灵活地更新对象值，并通过长期的经验稳定地保留它们。然而，目前还不清楚大脑如何编码这两种相互冲突的价值观，并相应地控制行为。我们发现灵长类动物尾状核的不同回路在灵活和稳定的价值条件下选择性地控制行为。单个尾状核神经元以区域不同的方式编码视觉对象的值：尾状核头部的灵活值编码和尾状核尾部的稳定值编码。猴子在这两种情况下都通过看具有更高价值的物体来适应。重要的是，每个尾状核亚区的失活在灵活或稳定的情况下选择性地破坏了高-低值区分。这种平行互补机制使动物能够在灵活和稳定的条件下选择有价值的物体。 外侧缰核（LHb）在动机决策中起着重要的作用。灵长类动物LHb中的神经元发出负的“奖励预测错误”信号，并抑制中脑多巴胺（DA）神经元。LHb中的这些负奖励预测误差信号至少部分地由苍白球内部段（GPb）的边界区域中的一组不同的神经元提供。然而，目前还不清楚是否其他基底神经节核团提供LHb的奖励信号，无论是通过GPB或通过不同的电路。作为回答这个问题的第一步，我们电刺激基底神经节的各个部分，并监测清醒猴子LHb的神经活动。首先，我们发现，低强度的刺激在GPb和苍白球（GPi）的内部段诱发LHb神经元的短潜伏期（5 ms）的兴奋性反应。第二，腹侧苍白球（VP）的刺激抑制LHb神经元。这些结果表明，奖励相关的信号主要通过兴奋性连接从GPb和抑制性连接从VP传递到LHb。最后，兴奋或抑制诱导LHb神经元从不同的，但在纹状体斑片状区域。这些作用具有相当长的潜伏期，表明它们可能由GPb或VP介导。刺激效应的斑块性质增加了这样一种可能性，即纹状体是传递给LHb的奖励相关信号的来源。 中脑中的多巴胺（DA）神经元对于行为的动机控制至关重要。然而，最近的研究表明，DA神经元传递的信号是异质的。这可能反映了DA神经元的广泛输入，但哪些信号由哪些大脑区域提供仍然不清楚。在这里，我们专注于脚桥被盖核（PPTg）在猕猴和特点的输入DA神经元。由于PPTg投射到许多大脑区域，因此识别投射到DA神经元区域的PPTg神经元至关重要。为此，我们使用逆向激活技术，通过电刺激三个位置（内侧，中央，外侧）在黑质pars延髓（SNc）。我们发现SNc投射神经元主要位于PPTg，楔状核也有一些。电刺激SNc投射的PPTg区域在假定的DA神经元中诱导尖峰脉冲的爆发，表明PPTg-DA（SNc）连接是兴奋性的。行为任务和临床试验表明，SNc投射PPTg神经元编码奖励，感觉运动和唤醒/报警信号。重要的是，奖励相关的PPTg神经元倾向于投射到内侧和中央SNc，而感觉运动/唤醒/警觉相关的PPTg神经元倾向于投射到外侧SNc。大多数奖励相关的信号是积极的偏见：兴奋和抑制时，更好和更坏的奖励预期，分别。这些PPTg神经元倾向于保留奖励值信号，直到奖励结果之后，代表“价值状态”;这与DA神经元不同，DA神经元显示代表“价值变化”的相位信号。我们的数据，加上以前的研究，表明，PPTg神经元发送积极的奖励相关信号主要是到内侧中央SNc的DA神经元编码的动机值，和感觉运动/唤醒信号的外侧SNc的DA神经元编码的动机显着性。 基底神经节具有抑制和去抑制机制，使受试者能够选择有价值的对象和行动。值得注意的是，可以通过最近的经验灵活地确定值，或者通过长期的经验稳定地确定值。最近的研究表明，尾状核的头部和尾部选择性和差异处理灵活和稳定的视觉对象的价值观。这些信号通过黑质的不同部位被发送到上级丘，这样动物就会优先看高价值的物体，但方式不同。因此，依靠短期的价值记忆，尾状头回路允许受试者的目光预期地移动到最近有价值的物体上。依靠长期的价值记忆，尾状尾回路允许受试者的目光自动移动到先前有价值的物体上。基底神经节也包含作用值的等效平行机制。这种灵活稳定的并行机制的目标和行动的价值创造了一个高度适应性的决策系统。

Choosing valuable objects is critical for survival, but their values may change flexibly or remain stable. Therefore, animals should be able to update the object values flexibly by recent experiences and retain them stably by long-term experiences. However, it is unclear how the brain encodes the two conflicting forms of values and controls behavior accordingly. We found that distinct circuits of the primate caudate nucleus control behavior selectively in the flexible and stable value conditions. Single caudate neurons encoded the values of visual objects in a regionally distinct manner: flexible value coding in the caudate head and stable value coding in the caudate tail. Monkeys adapted in both conditions by looking at objects with higher values. Importantly, inactivation of each caudate subregion disrupted the high-low value discrimination selectively in the flexible or stable context. This parallel complementary mechanism enables animals to choose valuable objects in both flexible and stable conditions. The lateral habenula (LHb) plays an important role in motivational decision making. Neurons in the primate LHb signal negative 'reward prediction errors' and inhibit midbrain dopamine (DA) neurons. These negative reward prediction error signals in the LHb are, at least partly, provided by a distinct group of neurons in the border region of the globus pallidus internal segment (GPb). However, it is still unclear whether other basal ganglia nuclei provide the LHb with reward signals, either through the GPb or through different circuits. As a first step to answer this question, we electrically stimulated various parts of the basal ganglia and monitored the neural activity in the LHb in the awake monkey. First, we found that low intensity stimulations in the GPb and the internal segment of the globus pallidus (GPi) evoked a short latency (5 ms) excitatory response in LHb neurons. Second, LHb neurons were inhibited by stimulations in the ventral pallidum (VP). These results suggest that reward-related signals are transmitted to the LHb mainly through excitatory connections from the GPb and inhibitory connections from the VP. Finally, excitations or inhibitions are induced in LHb neurons from diverse but patchy regions in the striatum. These effects have considerably longer latencies, suggesting that they may be mediated by the GPb or the VP. The patchy nature of the stimulation effect raises the possibility that the striosomes are the source of reward-related signals transmitted to the LHb. Dopamine (DA) neurons in the midbrain are crucial for motivational control of behavior. However, recent studies suggest that signals transmitted by DA neurons are heterogeneous. This may reflect a wide range of inputs to DA neurons, but which signals are provided by which brain areas is still unclear. Here we focused on the pedunculopontine tegmental nucleus (PPTg) in macaque monkeys and characterized its inputs to DA neurons. Since the PPTg projects to many brain areas, it is crucial to identify PPTg neurons that project to DA neuron areas. For this purpose we used antidromic activation technique by electrically stimulating three locations (medial, central, lateral) in the substantia nigra pars compacta (SNc). We found SNc-projecting neurons mainly in the PPTg, and some in the cuneiform nucleus. Electrical stimulation in the SNc-projecting PPTg regions induced a burst of spikes in presumed DA neurons, suggesting that the PPTg-DA (SNc) connection is excitatory. Behavioral tasks and clinical tests showed that the SNc-projecting PPTg neurons encoded reward, sensorimotor and arousal/alerting signals. Importantly, reward-related PPTg neurons tended to project to the medial and central SNc, whereas sensorimotor/arousal/alerting-related PPTg neurons tended to project to the lateral SNc. Most reward-related signals were positively biased: excitation and inhibition when a better and worse reward was expected, respectively. These PPTg neurons tended to retain the reward value signal until after a reward outcome, representing 'value state'; this was different from DA neurons which show phasic signals representing 'value change'. Our data, together with previous studies, suggest that PPTg neurons send positive reward-related signals mainly to the medial-central SNc where DA neurons encode motivational values, and sensorimotor/arousal signals to the lateral SNc where DA neurons encode motivational salience. The basal ganglia are equipped with inhibitory and disinhibitory mechanisms that enable a subject to choose valuable objects and actions. Notably, a value can be determined flexibly by recent experience or stably by prolonged experience. Recent studies have revealed that the head and tail of the caudate nucleus selectively and differentially process flexible and stable values of visual objects. These signals are sent to the superior colliculus through different parts of the substantia nigra so that the animal looks preferentially at high-valued objects, but in different manners. Thus, relying on short-term value memories, the caudate head circuit allows the subject's gaze to move expectantly to recently valued objects. Relying on long-term value memories, the caudate tail circuit allows the subject's gaze to move automatically to previously valued objects. The basal ganglia also contain an equivalent parallel mechanism for action values. Such flexible-stable parallel mechanisms for object and action values create a highly adaptable system for decision making.