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的感觉表征中起着重要作用， 从而形成我们的感知，我们所知道的大多数都是通过电生理学决定的。 在体外或在麻醉的大脑中研究丘脑。丘脑活动的特性，如平均 放电频率、定时和同步性以及紧张性/爆发性放电直接决定了感觉输入的表现方式 大脑皮层的时空激活通过基线水平的变化来调节丘脑“状态” 去极化强烈地影响感觉信号到皮层的动态中继的门控特性， 正常的行为利用清醒小鼠的触须路径，我们的团队处于独特的位置， 量化和控制丘脑状态，并测量对时空皮层的下游影响 表示，使用一系列多尺度电生理和光学测量，因果 操作、建模和感官行为任务。我们将首先确定丘脑国家控制 清醒小鼠的感觉信息处理（目标1）。一系列独立的实验将利用 单个单位和跨丘脑和S1的LFP记录以及宽场遗传表达电压传感器 在S1成像，以充分捕捉和模拟丘脑放电，同步和 清醒大脑中的紧张性/爆发性放电。然后，我们将进行与目标1平行的实验， 光遗传学操纵丘脑状态，以确定丘脑放电模式对 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 控制感官知觉的行为，在一个明确的晶须检测和空间（两个晶须） 辨别任务（目标3），采用相同的电生理学/成像和光遗传学操作 如在目标1和2中那样，通过丘脑和皮层的方法。意义：丘脑皮层回路是 由调制输入持续控制，从根本上塑造与 感知和行为。然而，丘脑状态和所产生的感受器之间的精确联系仍然是一个问题。 神经科学中的一个重要的开放性问题我们将确定皮层表征如何通过 丘脑输入的调制及其对感知的影响。广泛影响：大脑功能障碍 国家已经牵连在一个令人难以置信的广泛的神经系统疾病，从功能障碍， 发作性睡病中的觉醒到情绪障碍如抑郁症中的神经调质功能障碍。此外，委员会认为， 最近的全基因组关联研究表明， 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风险位点。最后还 主张理解大脑状态和感觉表征之间的相互作用是必要的， 假体中替代输入的递送。

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.