Corticofugal control of brainstem sensory gating in the rodent whisker system

啮齿类动物通过使用它们的大触须或胡须来探索它们周围的环境，同时表现出广泛的行为。在一种被称为主动触摸的特定行为中，它们用胡须探索物体，并操纵这些触觉传感器的位置，以获取有关物体的最大信息。在这种接触中，感觉处理与静止时期相比发生了变化。具体来说，三叉神经复合体的触觉反应神经元的感觉反应减少。相比之下，在没有胡须运动的情况下，被动接触物体会引起这些神经元的强烈反应。这种感觉门控显然可以最大限度地检测到附近的意外物体。最近的研究表明，通过脑干三叉神经核的门控是由皮质输入介导的，皮质输入对三叉神经回路进行差异调节。初级体感皮层（S1隔）特定区室的神经元增加三叉脑干的感觉传递，而次级体感皮层（S2）抑制它。然而，这一计划的几个关键因素仍有待阐明。首先，从鼻中隔到三叉神经复合体的投影从未在解剖学上确定过。其次，在清醒行为的动物中，三叉神经核在主动触摸/静止时的反应尚未被表征。第三，三叉神经核皮层投射对知觉的调节作用从未被测试过。在本提案中，我们的目标是通过利用解剖束追踪，神经生理记录，光遗传学和行为方法的组合方法来澄清这些观点。首先，我们将确定并量化从S1间隔到三叉神经核的投射。其次，我们将记录同一只清醒动物的三叉神经核和皮层，并表征三叉神经在不同行为状态下的反应。交叉相关分析将用于研究它们对皮质驱动的依赖。最后，我们将光遗传学操纵三叉神经核中的S1和S2受体结构，并量化随后的感知变化。这将是首次尝试在清醒动物脑干中自上而下表征皮层对须相关触觉门控的影响，并对皮层对感知的影响的研究具有重要意义。

Rodents exhibit a wide repertoire of behaviors whilst exploring their immediate environment through the use of their large vibrissae or whiskers. In a specific behavior, known as active touch, they explore objects with their whiskers and manipulate the position of these tactile sensors to extract maximal information about the object. During such contacts, sensory processing is altered as compared to periods of quiescence. Specifically, the sensory responses in the tactile responsive neurons of the trigeminal complex are reduced. By contrast, passive contacts with an object in the absence of whisker movements evoke large responses in these neurons. Such sensory gating apparently maximizes detection of unexpected objects in the vicinity. Recent studies suggest that gating through brainstem trigeminal nuclei is mediated by corticofugal inputs which differentially modulate trigeminal circuitry. Neurons in specific compartments of primary somatosensory cortex (S1 septa) increase sensory transmission through the trigeminal brainstem whereas secondary somatosensory cortex (S2) inhibits it. However, several key factors in such a scheme remain to be elucidated. First, the projections from septa to the trigeminal complex have never been anatomically determined. Second, the responses of the various trigeminal nuclei in an awake behaving animal during active touch/quiescence have not been characterized. Third, the effect of modulatory influence of cortical projections on trigeminal nuclei on perception has never been tested. In this proposal we aim to clarify these points via a combined approach utilizing anatomical tract tracing, neurophysiological recordings, optogenetics and behavioral methods. First, we will determine and quantify the projections from S1 septa to the trigeminal nuclei. Second, we will record from these trigeminal nuclei and cortex in the same awake animal and characterize trigeminal responses in the different behavioral states. Cross correlation analysis will be applied to study their dependence on cortical drive. Finally, we will optogenetically manipulate S1 and S2 recipient structures in the trigeminal nuclei and quantify ensuing changes in perception. This will be the first attempt to characterize top down, cortical influences on whisker-related tactile gating in the brainstem in an awake animal and has important implications in the study of cortical effects on perception.