Thalamocortical state control of tactile sensing: Mechanisms, Models, and Behavior

触觉感觉的丘脑皮质状态控制：机制、模型和行为 尽管感觉丘脑在形成皮层中的感觉表征方面起着重要作用，但 因此塑造了我们的感知，我们所知道的大部分都是通过电生理决定的 丘脑的体外或麻醉脑内的研究。丘脑活动的属性，如平均值 放电频率、定时和同步性以及强直/爆发式放电直接决定感觉输入的表示方式 在大脑皮质的时空激活中。基线水平变化对丘脑“状态”的调节作用 去极化强烈影响感觉信号向大脑皮层传递的门控特性 行为正常。利用清醒老鼠的触觉通路，我们的团队独特地定位于准确地 量化和控制丘脑状态，并测量对时空皮质的下游影响 使用一系列多尺度电生理和光学测量的表示法，原因 操作、建模和感觉行为任务。我们将首先确定丘脑状态控制 清醒小鼠的感觉信息处理(目标1)。一系列单独的实验将利用 跨丘脑和S1的单单位和LFP记录以及广域遗传表达电压传感器 在S1中成像，以完全捕获和模拟丘脑的激发、同步和 在清醒的大脑中产生强直/爆发式放电。然后我们将进行与目标1平行的实验，在该实验中我们 光遗传学操作丘脑状态，以确定丘脑放电模式在 大脑皮层感觉输入的时空表征(目标2)。最后，我们将确定丘脑状态 在明确定义的胡须检测和空间(两个胡须)中控制行为中的感官感知 辨别任务(目标3)，采用相同的电生理/成像和光基因操作 如目标1和目标2中那样穿过丘脑和皮质。意义：丘脑皮质回路是 由调制输入连续控制，该调制输入从根本上塑造了与 感知和行为。然而，丘脑状态和由此产生的知觉之间的确切联系仍然是 神经科学中的重大悬而未决的问题。我们将确定大脑皮层表示如何通过 丘脑输入的调制及其对知觉的影响。广泛的影响：大脑功能障碍 国家已经牵涉到了令人难以置信的广泛的神经疾病，从功能障碍 发作性睡病患者对抑郁等情绪障碍患者神经调节剂功能障碍的唤醒作用。此外， 最近的全基因组关联研究表明，在大脑中发现了电压门控钙通道 包括丘脑和皮质在内的结构是精神分裂症和双相情感障碍的危险部位。最后，我们还 断言了解大脑状态和感觉表征之间的相互作用是必要的 假体中代理输入的交付。

Thalamocortical state control of tactile sensing: Mechanisms, Models, and Behavior Despite the fact that the sensory thalamus plays a major role in shaping sensory representations in cortex, and thus shaping our percepts, most of what we know has been determined through electrophysiological investigation of the thalamus in-vitro or in the anesthetized brain. Properties of thalamic activity such as mean firing rates, timing and synchrony, and tonic/burst firing directly determine how sensory inputs are represented in the spatiotemporal activation of cortex. Modulations in thalamic “state” through changes in baseline levels of depolarization strongly influence the gating properties of the dynamic relay of sensory signals to cortex during normal behavior. Using the vibrissa pathway of the awake mouse, our team is uniquely positioned to precisely quantify and control thalamic state, and measure the downstream impact on spatiotemporal cortical representations, using a range of multi-scale electrophysiological and optical measurements, causal manipulations, modeling, and sensory behavioral tasks. We will first Determine Thalamic State Control of Sensory Information Processing in the awake mouse (Aim 1). A range of separate experiments will utilize single unit and LFP recording across thalamus and S1 and widefield genetically expressed voltage sensor imaging in S1 to fully capture and model the range of modulations in thalamic firing, synchronization, and tonic/burst firing in the awake brain. We will then conduct experiments that parallel Aim 1 in which we optogenetically manipulate thalamic state, to determine the causal role of thalamic firing modes on spatiotemporal representations of sensory inputs in cortex (Aim 2). Finally, we will Determine Thalamic State Control of Sensory Percepts in behavior, in a well-defined whisker detection and spatial (two-whisker) discrimination tasks (Aim 3), employing the same electrophysiology/imaging and optogenetic manipulation approaches across thalamus and cortex as in Aims 1 and 2. Significance: The thalamocortical circuit is continuously controlled by modulatory inputs that fundamentally shape information processing relevant for perception and behavior. However, the precise link between thalamic state and the resultant percept remains a major open question in neuroscience. We will determine how cortical representations changes through modulation in thalamic input and the consequences of this on perception. Broad Impacts: Dysfunction of brain state has been implicated in an incredibly wide range of neurological disorders ranging from dysfunction of arousal in narcolepsy to dysfunction of neuromodulators in mood disorders such as depression. Furthermore, recent genome wide association studies have implicated voltage-gated calcium channels found in brain structures including thalamus and cortex as risk loci for both schizophrenia and bipolar disorder. Finally, we also assert that understanding of the interaction between brain state and sensory representations is requisite for delivery of surrogate inputs in prostheses.