Parafascicular Nucleus: Its Role in Cortical and Striatal Salience Encoding

描述（由申请人提供）：感知和定位新信息的能力对生存至关重要。丘脑中央正中核和束旁核（CM/Pf）被假设在注意定向的感觉运动过程中起着关键作用。最近的研究表明，有关突出感觉输入的信息通过CM/Pf传递到前脑目标，在那里它可以中断正在进行的处理并将注意力重新引导到突出刺激上。拟议的研究将通过评估CM/Pf中感觉处理对其新皮层和基底神经节中下游靶点的具体影响来测试这一假设，使用相关，因果（光遗传学）和行为测量的组合。在小鼠中，外侧和内侧Pf分别与灵长类动物的CM（感觉运动）和Pf（联合）丘脑核同源。我们将系统地测试小鼠外侧Pf活动对初级体感新皮层（SI）和背外侧（感觉运动）纹状体（DLS）的刺激表征的影响，使用2-触须刺激范例，其中每个刺激的显着性根据其发生的概率进行操纵。在目的I中，将使用基因修饰的小鼠系进行体内细胞外记录，所述基因修饰的小鼠系使我们能够特异性地识别SI和DLS中的罕见神经元亚型，已知Pf投射到所述神经元亚型上以形成突触。在目的II和III中，将使用光遗传学方法来用光激活膜蛋白来抑制侧Pf中的投射神经元，所述光激活膜蛋白允许这些神经元的时间精确刺激或沉默。在Aim II中使用轻度麻醉的小鼠，SI和DLS中的细胞外记录将与试验子集中Pf中的光学刺激相结合，提供Pf激发对低概率（突出）和高概率（非突出）刺激的下游刺激表征的影响的因果测试。在目标IIIB中，在头部固定检测任务期间在清醒小鼠中进行的类似实验将测试Pf在行为相关刺激检测期间的影响。通过测试Pf对同传和DLS中显著性表征的影响，拟议的研究将批判性地检验广泛假设的Pf在注意定向中的作用。

DESCRIPTION (provided by applicant): The ability to perceive and orient to new information is crucial to survival. The centre median and parafascicular nuclei (CM/Pf) of the thalamus are hypothesized to play a critical role in the sensorimotor process of attentional orienting. Recent studies have suggested that information about salient sensory input is relayed through CM/Pf to forebrain targets, where it serves to interrupt ongoing processing and redirect attention to the salient stimulus. The proposed research will test this hypothesis by assessing the specific impact of sensory processing in CM/Pf on its downstream targets in neocortex and basal ganglia using a combination of correlative, causal (optogenetic) and behavioral measures. In the mouse, lateral and medial Pf are homologous to the CM (sensorimotor) and Pf (associative) thalamic nuclei of primates, respectively. We will systematically test the impact of mouse lateral Pf activity on stimulus representations in primary somatosensory neocortex (SI) and dorsolateral (sensorimotor) striatum (DLS) using a 2-vibrissa stimulation paradigm in which the salience of each stimulus is manipulated according to its probability of occurrence. In Aim I, in vivo extracellular recordings will be performed using genetically modified mouse lines that enable us to specifically identify rare subtypes of neurons in SI and DLS onto which Pf projections are known to synapse. In Aims II and III, an optogenetic approach will be used to transduce the projection neurons in lateral Pf with light-activated membrane proteins that allow temporally precise stimulation or silencing of these neurons. Using lightly anesthetized mice in Aim II, extracellular recording in SI and DLS will be combined with optical stimulation in Pf on a subset of trials, providing causal testing of the impact of Pf firing on downstream stimulus representations for both low-probability (salient) and high-probability (non- salient) stimuli. In Aim IIIB, similar experiments performed in awake mice during the head-fixed detection task will test the impact of Pf during behaviorally relevant stimulus detection. By testing the impact of Pf on salience representations in SI and DLS, the proposed studies will critically examine the widely hypothesized role of Pf in attentional orienting.