MALADAPTIVE REORGANIZATION OF INHIBITORY CIRCUITS IN NEOCORTICAL MALFORMATION

新皮质畸形中抑制回路的适应不良重组

• 批准号: 7610193
• 负责人: Qian-Quan Sun
• 金额: $ 2.57万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610193
• 关键词: Brain; Cerebral cortex; Chromosome Pairing; Computer Retrieval of Information on Scientific Projects Database; Condition; Cortical Dysplasia; Depth; Development; Dyslexia; Epilepsy; Equilibrium; Fragile X Syndrome; Funding; Glutamates; Grant; Inhibitory Synapse; Institution; Interneurons; Intervention; Microscopic; Modification; Neurons; Process; Property; Regulation; Research; Research Design; Research Personnel; Resources; Role; Schizophrenia; Source; Synapses; System; Time; Translating; United States National Institutes of Health; excitatory neuron; experience; in vivo; insight; malformation; neocortical; nervous system disorder; postnatal; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During early brain development, neurons in the cerebral cortex establish connections that are then fine tuned by experience-dependent mechanisms. Although much is now known regarding processes of glutamatergic maturation and activity-dependent modification of glutamatergic synapses for network formation, postnatal development of neocortical GABAergic synapses and their role in activity-dependent modification remains unclear. The proposed research will utilize a combination of electrophysiologic recording and microscopic analyses to examine how developmental changes of inhibitory synapses and interneuron network properties are translated into a mature, functional cortical system. By studying the developmental regulation of spike-timing dependent plasticity of glutamatergic synapses in interneurons and excitatory neurons, we will have a deeper understanding of the mechanisms involved in the activity-dependent maturation of brain inhibitory circuits in vivo. This type of study will bridge the gap between the experiencedependent plasticity of synapses and the maturation of functional relevant neocortical circuits. This type of study will certainly help us gain further insights into the mechanisms underlying several developmentally related neurological disorders such as autisms, Fragile X syndrome, cortical dysplasia, schizophrenia, epilepsy and dyslexia, in which early endogenous and exogenous unfavorable conditions create a long-lasting impact on the mature cortex. Successful completion of these experiments will also help to identify potential targets for pharmacological intervention of disturbances in excitation and inhibition balancing.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在早期大脑发育过程中，大脑皮层中的神经元建立了连接，然后通过经验依赖性机制进行了微调。尽管现在已经知道了谷氨酸能成熟的过程以及谷氨酸能突触的活动依赖性改性，以进行网络形成，但新皮层GABAergic突触的产后发展及其在活动依赖性修饰中的作用尚不清楚。拟议的研究将利用电生理记录和微观分析的组合来检查抑制突触的发育变化如何转化为成熟的功能性皮质系统。通过研究中间神经元和兴奋性神经元中谷氨酸能突触的峰值依赖性可塑性的发育调节，我们将对体内脑抑制回路的活性成熟所涉及的机制有更深入的了解。这类研究将弥合突触的经验可塑性与功能相关的新皮质回路的成熟之间的差距。这类研究无疑将有助于我们进一步了解几种与发育相关的神经系统疾病的机制，例如自闭症，脆弱的X综合征，皮质发育不良，精神分裂症，癫痫和癫痫症，在这种机制中，早期内源性和外源性的内源性和外源性不利的疾病会对成熟的Cortex产生长期的影响。这些实验的成功完成还将有助于确定激发和抑制平衡中的药理学干预措施的潜在目标。