Parafascicular Nucleus: Its Role in Cortical and Striatal Salience Encoding

描述（由申请人提供）：感知和适应新信息的能力对生存至关重要。假设丘脑的中心、中间和束旁核（CM/Pf）在注意定向的感觉运动过程中起关键作用。最近的研究表明，关于显著感觉输入的信息通过CM/Pf传递到前脑目标，在那里它中断正在进行的处理，并将注意力转移到显著刺激上。本研究将采用相关、因果（光遗传学）和行为测量相结合的方法，评估CM/Pf中感觉加工对其下游靶细胞新皮层和基底神经节的具体影响，从而验证这一假设。在小鼠中，外侧核和内侧核分别与灵长类丘脑的感觉运动核和联合核同源。我们将系统地测试小鼠侧Pf活动对初级体感觉新皮层（SI）和背外侧（感觉运动）纹状体（DLS）刺激表征的影响，使用2-触须刺激范式，其中每个刺激的显著性根据其发生的概率进行操纵。在Aim I中，体内细胞外记录将使用转基因小鼠系进行，使我们能够特异性地识别SI和DLS中罕见的神经元亚型，这些神经元亚型已知与Pf投射相连接。在Aims II和III中，将使用光遗传学方法用光激活膜蛋白转导侧Pf中的投射神经元，从而允许对这些神经元进行暂时精确的刺激或沉默。在Aim II中，使用轻度麻醉的小鼠，在SI和DLS中的细胞外记录将与Pf中的光学刺激相结合，为Pf放电对低概率（显著）和高概率（非显著）刺激的下游刺激表征的影响提供因果测试。在Aim IIIB中，在固定头部检测任务中对清醒小鼠进行类似的实验，将测试Pf在行为相关刺激检测中的影响。通过测试Pf对SI和DLS中显著表征的影响，提出的研究将批判性地检验Pf在注意定向中的广泛假设作用。

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.