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。丘脑的中央、中核和束旁核(CM/Pf)被认为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传递到前脑靶点，在那里它起到中断正在进行的处理并将注意力重新定向到显著刺激的作用。这项拟议的研究将通过结合相关、因果(光遗传)和行为测量来评估CM/PF中感觉加工对新皮质和基底节下游靶标的具体影响，以检验这一假说。在小鼠，外侧核和内侧核分别与灵长类动物丘脑的CM(感觉运动)核和PF(联合)核同源。我们将使用双触觉刺激范式系统地测试小鼠外侧PF活动对初级躯体感觉新皮质(SI)和背外侧(感觉运动)纹状体(DLS)刺激表征的影响，在该范式中，每个刺激的显著程度是根据其发生的概率来操纵的。在目标I中，将使用转基因小鼠品系进行体内细胞外记录，这使我们能够专门识别SI和DLS中已知的PF投射到其上的罕见神经元亚型。在AIMS II和III中，将使用光遗传学方法转导外侧PF的投射神经元，这些投射神经元具有光激活的膜蛋白，允许对这些神经元进行时间上的精确刺激或沉默。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PF中的光刺激相结合，进行子集试验，提供对低概率(显著)和高概率(非显著)刺激的PF放电对下游刺激表示的影响的因果测试。在AIM IIIB中，在头部固定检测任务中在清醒小鼠身上进行的类似实验将测试PF在行为相关刺激检测过程中的影响。通过测试PF对同感和DLS中显著表征的影响，本研究将批判性地检验被广泛假设的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.