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

项目总结 抑制性丘脑网状核(TRN)包裹在丘脑背侧。TRN已经准备好进入丘脑- 皮层信号通过与丘脑背侧的双向连接，并作为单向信号的接收者 来自整个大脑皮层的通路。我们之前发现了三个相互关联的区域 灵长类、丘脑内侧背侧核(MD)、特定的前额叶皮质(PFC)和杏仁核支配 额叶，以及感觉性TRN部分。这一证据表明前额控制注意力有助于提高注意力。 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 评估目前尚不清楚的连接TRN和丘脑背侧核的微电路，它引起层流- 通向大脑皮层的特定路径。这些研究是基于灵长类的专门化，这可能是正常的基础。 以及通过丘脑和大脑皮质的病理功能。我们的工作假设是 神经化学上不同的抑制性TRN神经元在TRN内有特定的突触相互作用。在……里面 此外，不同的抑制性TRN神经元与丘脑的“核心”神经元有特殊的联系 局灶性地驱动中间皮质层的活动，以及广泛神经支配的“基质”丘脑神经元 上层大脑皮层。实验旨在通过系统的研究来验证这一假说：(1) TRN区内不同神经化学特征的TRN神经元的分子和突触组织；(2)通路 TRN来源：一个模型感觉丘脑核团，视觉外侧膝状体，与视觉相连 大脑皮质；以及模型高阶丘脑核MD，它与PFC和杏仁核相连； TRN通路指向这些丘脑背侧核中的每一个；(4)和使用从 兴奋和抑制回路，模拟TRN和背侧丘脑的正常功能，以及干扰 在疾病中。将使用相同的高分辨率方法来研究恒河猴和 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与丘脑背侧核的双向回路以可靠地将它们与其他核分开 小路。定量分析将基于相关的共聚焦和电子显微镜的数据，以及 三维重建路径和突触的多尺度分辨率。关于路径的假说 交互作用基于关于皮质丘脑网络组织的理论框架和 在灵长类动物中，TRN与背侧丘脑和皮质平行地显著扩张和特化。 这些研究结果将为TRN和丘脑皮质系统在脑内的作用提供回路基础。 感觉、认知和情绪过程的注意调节及其对睡眠障碍和睡眠障碍的干扰 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.