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。在动眼轴的许多视觉运动结构中，神经元释放最初的“视觉”活动爆发来记录视觉刺激，随后“运动”爆发触发运动，将视觉轴重定向到感兴趣的物体。考虑到这些神经元投射到脑干中产生扫视的回路，一个长期存在的感觉运动转换之谜是，为什么视觉反应不足以触发运动，而第二运动爆发却可以。一种主流理论认为，当活动达到阈值时，眼跳就会被触发。这种观点是不令人满意的，因为阈值水平也可能被视觉爆发所跨越，但不会触发眼跳。另一种理论认为，当神经活动的可变性减少时，运动就会发生。对这一假设的支持是基于在试验中测量的可变性。这不是一个可行的机制，神经元解码他们的输入尖峰来决定何时触发扫视。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——当放电率的增加与整个动眼神经轴的群体活动的“时间稳定性”相结合时，扫视开始发生。更具体地说，我们认为所有视觉运动元素的视觉爆发是不稳定的，因此

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?