Neural Mechanism for the assembly of GABAergic in the cerebral cortex

项目摘要 γ-氨基丁酸(GABA)能中间神经元功能障碍与神经学密切相关 精神障碍包括癫痫、精神分裂症和自闭症谱系障碍。尽管最近有证据表明 突出了这些神经元令人眼花缭乱的亚型多样性，即发育障碍在 亚型功能缺陷所致的皮质环路形成具有持续性功能缺陷尚未得到证实 进行了详细的探索。这项研究的长期目标是揭示早期神经元功能障碍是如何在 出生后大脑的发育会导致持久的神经病理。这项提议的目的是揭示 围产期发育关键窗口期特定中间神经元群体的活动如何形成 初级感官依赖行为的基础回路。 为此，我们将使用小鼠桶状皮质作为研究活动依赖的成熟模型。 电路成熟。我们将把研究集中在表面电路上，因为我们之前的工作表明，这些 神经回路对新生儿的环境干扰非常敏感。在短期内，这项提议 旨在研究I层中间神经元亚型在调节皮质突起中的作用。 栏目(目标1)。此外，这个项目将确定LI中间神经元在LI中间神经元的出现中的作用。 大脑半球间回路。(目标2)。最后，我们将评估早期LI中间神经元的发育缺陷 功能障碍导致成人大脑活动异常和感觉统合受损(目标3)。 关于结果，我们的工作预计将确定基本机制，为 健康的兴奋性/抑制性平衡的紧急情况。此外，这些结果预计将产生 显著的翻译影响，因为它们将扩展我们关于中间神经元多早的机制知识 功能障碍可能导致在ASD患者中常见的行为异常。

Project Summary Dysfunction of gamma-aminobutyric acid (GABA)ergic interneurons is strongly associated with neurological disorders including epilepsy, schizophrenia and autism spectrum disorders. Although recent evidence highlights bewildering subtype diversity of these neurons, the notion that developmental perturbations in subtype function cause defects in the formation of cortical circuits with lasting functional deficits has not been explored in detail. The long-term goal of this research is to uncover how early interneuron dysfunction in the developing postnatal brain leads to lasting neurological pathologies. The objective of this proposal is to reveal how the activity of specific interneuron populations during critical windows of perinatal development shape circuits underlying primary sensory-dependent behavior. To this end, we will use the murine barrel cortex as a well-established model for the study of activity-dependent circuit maturation. We will focus our studies in superficial circuits since our previous work indicates that these circuits are exquisitely sensitive to environmental perturbations in the neonate. In the near term, this proposal is aimed at investigating the role of layer I interneuron subtypes in regulating the emergence of cortical columns (Aim 1). In addition, this project will determine the role of LI interneurons in the emergence of interhemispheric circuits. (Aim 2). Finally, we will assess how developmental defects in early LI interneuron function lead to abnormal brain activity and impaired sensory integration in the adult (Aim 3). With respect to the outcomes, our work is expected to identify basic mechanisms fundamental for the emergency of a healthy excitatory/inhibitory balance. In addition, these results are expected to have a significant translational impact because they will expand our mechanistic knowledge on how early interneuron dysfunction may lead to behavioral abnormalities frequently observed in ASD patients.