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Molecular Control of Long-Range Fronto-Posterior Cortical Projection Maturation Mediating Attention

长程前后皮质投射成熟介导注意力的分子控制

基本信息

批准号：
9350170
负责人：
Elisa Nabel
金额：
$ 4.12万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9350170
关键词：
Address Adolescence Adolescent Adult Affect Anterior Area Attention Attention deficit hyperactivity disorder Attentional deficit Autistic Disorder Biological Assay Biological Neural Networks Cells Child Child Psychiatry Clinical Complex Development Diagnosis Discrimination Disease Distal Etiology Event Fellowship Foundations Functional disorder Future GPI Membrane Anchors Goals Impairment Intervention Knowledge Light Macaca Mediating Membrane MicroRNAs Molecular Monitor Mus Neurodevelopmental Disorder Neurons Nicotine Nicotinic Receptors Pharmacology Physiology Process Public Health Rabies Reaction Time Reporting Schizophrenia Secondary to Signal Transduction Snake Venoms Structural Protein Synapses System Testing Therapeutic Training Translations United States Viral Visual Visual Cortex Visual attention Visuospatial Work accurate diagnosis alpha Bungarotoxin base career cingulate cortex cognitive process disability emerging adult expectation extracellular frontal lobe genetic manipulation inhibitor/antagonist insight interdisciplinary approach intersectionality knock-down neural circuit neurobiological mechanism neurodevelopment neuropsychiatric disorder novel presynaptic prevent symptom cluster symptom management targeted treatment tool touchscreen

项目摘要

Project Summary Neuropsychiatric disorders with developmental origins affect more than 15% of children in the United States and poses a major public health concern requiring $35 billion a year to address in large part due to secondary disability. Clinical efforts to diagnose, treat, and monitor disease have been hindered because they rely on observations of non-specific clusters of symptoms, thus limiting current pharmacologic therapeutics to symptom management. Initial studies report that distal cortical areas fail to connect in these disorders, however, the development of more effective pharmacological interventions requires a better basic understanding of normal maturation and implicated pathophysiology. These processes can be examined in mice. Such work in our lab has identified a necessary driver of maturation—Lynx1— for a projection commonly impaired from the frontal cortex to the visual cortex that mediates visual attention processing. This proposal seeks to more fully examine how Lynx1 promotes normal neural development in this key cortical connection and will investigate the functional and structural consequences of aberrant development in the absence of this important molecule. I hypothesize that Lynx1, an endogenous nicotinic receptor inhibitor, regulates the integration of this projection into forming neural networks that enact visual attention. This pathophysiological insight will promote the development of more effective diagnosis and targeted therapies for neurodevelopmental disorders.

项目摘要发育性神经精神障碍影响美国超过15%的儿童，构成了一个重大的公共卫生问题，每年需要350亿美元来解决，这在很大程度上是由于残疾。临床上诊断、治疗和监测疾病的努力一直受到阻碍，因为他们依赖于对非特定症状群的观察，从而将当前的药物治疗局限于症状管理层。初步研究报告说，在这些疾病中，远侧皮质区域无法连接，然而，开发更有效的药理学干预措施需要更好地了解正常成熟和牵连的病理生理学。这些过程可以在小鼠身上进行检测。在我们实验室做这样的工作已经确定了成熟的必要驱动因素-Lynx1-对于通常从额叶受损的投射大脑皮层到视觉皮质，负责调节视觉注意的加工。这项建议旨在更全面地审查 Lynx1如何在这一关键的皮质连接中促进正常的神经发育，并将研究以及在缺乏这种重要分子的情况下异常发育的结构后果。我假设内源性尼古丁受体抑制物Lynx1调节这一投射整合到形成产生视觉注意力的神经网络。这种病理生理学的洞察力将促进对神经发育障碍进行更有效的诊断和靶向治疗。