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

Organization and Circuit Interactions of Thalamocortical Attentional Networks in Health and Disease
丘脑皮质注意网络在健康和疾病中的组织和回路相互作用
批准号:
10534664
负责人:
Arash Yazdanbakhsh
金额:
$46.09万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-02-15 至 2024-11-30

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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.
期刊论文(7)
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会议论文
DOI: 10.3389/fpsyt.2023.1199690
发表时间: 2023
期刊: FRONTIERS IN PSYCHIATRY
影响因子: 4.7
作者: [Zhu, Jiating, Zikopoulos, Basilis, Yazdanbakhsh, Arash]
通讯作者: Yazdanbakhsh, Arash
DOI: 10.1371/journal.pbio.3001612
发表时间: 2022-03
期刊: PLOS BIOLOGY
影响因子: 9.8
作者: [Hilgetag, Claus C., Zikopoulos, Basilis]
通讯作者: Zikopoulos, Basilis
DOI: 10.1111/ejn.15739
发表时间: 2022-08
期刊: The European journal of neuroscience
影响因子: --
作者: []
通讯作者:
Laminar Excitatory Inputs to the Dorsolateral Prefrontal Cortex: Implications for Periadolescent Synaptic Plasticity and Circuit Pathology.
背外侧前额叶皮层的层流兴奋性输入:对青春期突触可塑性和回路病理学的影响。
DOI: 10.1016/j.biopsych.2023.06.005
发表时间: 2023
期刊: Biological psychiatry
影响因子: 10.6
作者: [Medalla,Maria, Zikopoulos,Basilis]
通讯作者: Zikopoulos,Basilis
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    Organization and Circuit Interactions of Thalamocortical Attentional Networks in Health and Disease
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