Neural Mechanisms of Saccade Initiation

描述（由申请人提供）：感觉运动转化是生存的基础。眼轴上的许多视觉结构中的神经元释放最初的"视觉"活动爆发以记录视觉刺激，随后释放"运动"爆发以触发将视觉轴重定向到感兴趣对象的运动。鉴于这些神经元投射到脑干中的扫视产生电路，感觉运动转换的一个长期存在的谜团是为什么视觉反应不足以触发运动，而第二次运动爆发却可以。一个主要的理论指出，当活动达到阈值时，眼跳被触发。这个视图是不令人满意的，因为视觉突发也可以越过阈值水平，但不会触发扫视。另一种理论认为，当神经活动的可变性降低时，运动开始发生。对这一假设的支持是基于试验间测量的变异性。这不是一个可行的机制，神经元解码其输入尖峰，以决定何时触发眼跳。理想情况下，解码必须基于试验中的神经活动结构。我们提出了一个创新的观点-我们的中心假设-眼跳启动时发生的射击率的增加，再加上“时间稳定性”的人口活动在整个眼神经轴。更具体地说，我们认为，在所有视觉元素的视觉爆发是不稳定的，因此， 不能触发扫视，而前运动爆发是稳定的，并在放电率超过阈值时启动运动。 时间稳定性是由一个度量来定义的，该度量跟踪在由同时或连续记录的神经元群体定义的归一化神经轨迹内作为时间的函数的相似性或一致性。从上级丘和额叶眼场神经元记录的延迟扫视任务的初步数据表明，放电率是不稳定的瞬态视觉反应，但保持稳定的运动前爆发之前扫视发作。我们建议解决以下新出现的问题，使用电生理和计算方法相结合：什么是动态的时间稳定性配置文件时，视觉和运动爆发重叠或合并，如在反应和表达眼跳，分别？当分析同时记录的许多神经元时，时间稳定性是否表现出类似的特性？从不同试验中获得关于神经变异性的见解（例如，Fano因子、最优子空间）和试验内（时间稳定性）分析是相辅相成的吗？如何在通用下游神经元中实现时间稳定性？如何将这种解码器算法纳入扫视控制的电路级模型中？

DESCRIPTION (provided by applicant): Sensorimotor transformation is fundamental for survival. Neurons in many visuomotor structures in the oculomotor axis discharge an initial "visual" burst of activity to register the visual stimulus and later a "motor" burst to trigger a movement that redirects the visual axis to the object of interest. Given that such neurons project to the saccade generating circuitry in the brainstem, a long standing enigma of sensorimotor transformation is why the visual response is insufficient to trigger a movement while the second motor burst is. One leading theory states that the saccade is triggered when activity reaches a threshold. This view is unsatisfactory because the threshold level could be crossed by the visual burst also but without triggering a saccade. Another theory contends that movement onset occurs when variability in neural activity is reduced. Support for this hypothesis is based on variability measured across trials. This is not a feasible mechanism for neurons decoding their input spikes to decide when to trigger a saccade. Ideally, the decoding must be based on the structure of neural activity within a trial. We propose an innovative perspective - our central hypothesis - that saccade initiation occurs when an increase in firing rate is coupled with "temporal stability" in the population activity throughout the oculomotor neuraxis. More specifically, we suggest that the visual burst in all visuomotor elements is unstable and therefore cannot trigger a saccade, while the premotor burst is stable and initiates the movement when the firing rate crosses a threshold. Temporal stability is defined by a metric that tracks similarty or consistency as a function of time within a normalized neural trajectory defined by a population of neurons recorded either simultaneously or serially. Preliminary data from superior colliculus and frontal eye field neurons recorded sequentially during the delayed saccade task indicate that firing rate is unstable during the transient visual response but remains stable during the premotor burst that precedes saccade onset. We propose to address the following emerging questions using a combination of electrophysiological and computational approaches: What are the dynamics of temporal stability profile when visual and motor bursts overlap or merge, such as during reactive and express saccades, respectively? Does temporal stability exhibit similar properties when analyzed over many neurons recorded simultaneously? Do insights on neural variability obtained from across trials (e.g., Fano factor, optimal subspace) and within trials (temporal stability) analyses complement each other? How would temporal stability be implemented in a generic downstream neuron? How can this decoder algorithm be incorporated in a circuit-level model of saccade control?