Organization and Circuit Interactions of Thalamocortical Attentional Networks in Health and Disease

项目摘要 抑制性丘脑网状核（TRN）位于丘脑背侧。技术情报局准备进入塔勒莫- 皮质信号通过双向连接与背侧丘脑，并作为单向的受体 整个大脑皮层的神经通路我们之前发现，在大脑中有三个相互关联的区域， 在灵长类动物中，丘脑背内侧核（MD）、特定的前额叶皮质（PFC）和杏仁核受神经支配 额叶和感觉神经节这一证据表明，前额叶控制注意力有助于 为灵活的目标导向的行为选择显著的刺激。这些事态发展突出表明，有必要系统地 评估迄今未知的微电路连接TRN与丘脑背核，这引起了层状- 大脑皮层的特定通路这些研究是基于灵长类动物的专业化，这可能是正常的 以及人类丘脑和皮层的病理功能。我们的假设是 神经化学上不同的抑制性TRN神经元在TRN内具有特定的突触相互作用。在 此外，不同的抑制性TRN神经元与“核心”丘脑神经元有专门的联系， 局灶性驱动皮质中层的活动，以及广泛支配 上层皮质层本文通过系统研究以下几个方面来验证这一假设：（1） TRN扇区内神经化学上不同的TRN神经元的分子和突触组织;（2）通路 TRN来自：一个模型感觉丘脑核，视觉外侧膝状体，它与视觉连接 （3）丘脑高级核（MD）与前额叶皮层和杏仁核相连; TRN通路直接到这些背侧丘脑核中的每一个;（4）和使用丰富的数据库， 兴奋性和抑制性回路，以模拟TRN和背侧丘脑内的正常功能， 疾病。相同的高分辨率方法将用于研究恒河猴和 人类兴奋性和抑制性通路将使用分子、细胞和突触特征进行标记， 区分TRN与丘脑背核的双向回路，以可靠地将它们与其他回路分开。 途径。定量分析将基于相关的共聚焦和电子显微镜的数据， 在多个分辨率尺度上对通路和突触进行3D重建。关于pathway的假设 相互作用是基于一个理论框架的组织皮质丘脑网络和 在灵长类动物中，TRN与背侧丘脑和皮质平行地显著扩展和特化。 这些研究的结果将为TRN和丘脑皮质系统在脑内活动中的作用提供电路基础。 对感觉、认知和情绪过程的注意力调节及其在睡眠障碍中的破坏， 精神分裂症和自闭症的注意力缺陷。

PROJECT SUMMARY The inhibitory thalamic reticular nucleus (TRN) envelops the dorsal thalamus. The TRN is poised to gate thalamo- cortical signals through two-way connections with the dorsal thalamus, and as the recipient of unidirectional pathways from the entire cerebral cortex. We previously discovered that three interconnected regions in primates, the mediodorsal thalamic nucleus (MD), specific prefrontal cortices (PFC) and the amygdala innervate the frontal, as well as the sensory TRN sectors. This evidence suggests prefrontal control of attention to help select salient stimuli for flexible, goal directed behavior. These developments highlight the need to systematically evaluate the as-yet unknown microcircuitry linking TRN with dorsal thalamic nuclei, which give rise to laminar- specific pathways to cortex. These studies are predicated on primate specializations that may underlie normal and pathologic function through thalamus and cortex in humans. Our working hypothesis is that neurochemically-distinct inhibitory TRN neurons have specific synaptic interactions within TRN. In addition, distinct inhibitory TRN neurons have specialized connections with ‘core’ thalamic neurons that focally drive activity in the middle cortical layers, and ‘matrix’ thalamic neurons that broadly innervate the upper cortical layers. Experiments are designed to test this hypothesis by systematic study of: (1) the molecular and synaptic organization of neurochemically-distinct TRN neurons within TRN sectors; (2) pathways to TRN from: a model sensory thalamic nucleus, the visual lateral geniculate, which is connected with the visual cortex; and a model high-order thalamic nucleus, the MD, which is connected with PFC and the amygdala; (3) TRN pathways directed to each of these dorsal thalamic nuclei; (4) and use of the rich database obtained on excitatory and inhibitory circuits to simulate normal function within the TRN and dorsal thalamus, and disruption in disease. Identical high-resolution methods will be used to study pathway interactions in rhesus monkeys and humans. Excitatory and inhibitory pathways will be labeled using molecular, cellular and synaptic features that differentiate bidirectional circuits of TRN with dorsal thalamic nuclei to reliably separate them from other pathways. Quantitative analyses will be based on data from correlated confocal and electron microscopy, and 3D-reconstruction of pathways and synapses at multiple scales of resolution. Hypotheses about pathway interactions are based on a theoretical framework on the organization of corticothalamic networks and the significant expansion and specialization of TRN in parallel with the dorsal thalamus and cortex in primates. Findings from these studies will provide the circuit basis for the role of TRN and the thalamocortical systems in attentional modulation for sensory, cognitive and emotional processes and their disruption in sleep disorders and attention deficits in schizophrenia and autism.