Intertectal input shapes visual circuit development and post injury remodeling

顶盖间输入塑造视觉回路发育和损伤后重塑

• 批准号: 8876832
• 负责人: Abigail Gambrill
• 金额: $ 5.6万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8876832
• 关键词: Address; Affect; Animals; Area; Autistic Disorder; Axon; Behavior; Behavioral; Biological Neural Networks; Brain; Brain Injuries; Brain region; Commissure; Communication; Complex; Contralateral; Development; Disease; Dissection; Electrophysiology (science); Environment; Food; Foundations; Glutamates; Health; Homologous Gene; Injury; Lobe; Mediating; Methods; Modality; Modeling; Molecular Genetics; Motor; Motor output; N-Methylaspartate; Neurons; Optics; Organism; Output; Plastics; Preparation; Probability; Process; Property; Protocols documentation; Recovery; Retinal; Role; Schizophrenia; Sensory Process; Series; Shapes; Speed; Stimulus; Stroke; Synapses; Synaptic Transmission; System; Tadpoles; Techniques; Tectum Mesencephali; Testing; Time; Translating; Traumatic Brain Injury; Vertebrates; Vision; Visual; Work; Xenopus; avoidance behavior; base; genetic manipulation; information processing; injured; neural circuit; neurogenesis; prevent; receptor; repaired; research study; response; response to injury; retinotectal; sensory input; superior colliculus Corpora quadrigemina; visual information; visual motor; visual stimulus

DESCRIPTION (provided by applicant): Neural circuits used in sensory processing must be stable enough to mediate survival-critical behaviors, and yet plastic enough to adapt to a dynamic environment. While great progress has been made in understanding how single synapses adjust response strength, less is known about the mechanisms of circuit-level development and plasticity. In the proposed study, I will use electrophysiology to investigate the connections between the two hemispheres of the Xenopus optic tectum, and their role in circuit plasticity and maturation, both in the course of normal development and in response to injury. These connections are poorly understood, and their contribution to circuit development and plasticity is unknown. The optic tectum is homologous to the mammalian superior colliculus and is critical for processing sensory information from multiple modalities. These intertectal inputs are tectal neurons which extend axons across the commissure to synapse onto tectal neurons in the contralateral hemisphere. In the superior colliculus, it has been proposed that these inputs mediate reciprocal inhibition; however the cellular and circuit-level mechanisms underlying this function are unknown. We have developed a new dissection prep in order to allow us to specifically explore 1) how intertectal inputs develop in Xenopus and how these inputs contribute to circuit formation, 2) how changes in the strength of intertectal input affects retinotectal circuit formation and plasticity and, 3) the remodeling of these inputs, and their contribution to recovery post-injury. These experiments will not only address fundamental questions of how neural circuits are formed and maintained, but will provide crucial information on changes that occur in disease states wherein synaptic connectivity is disrupted, such as schizophrenia, stroke, and traumatic brain injury.

描述（由申请人提供）：感觉处理中使用的神经回路必须足够稳定，以介导至关重要的行为，但塑料足以适应动态环境。尽管在理解单个突触如何调整响应强度方面取得了巨大进展，但对电路级发育和可塑性的机制知之甚少。在拟议的研究中，我将使用电生理学研究爪蟾视神经膜的两个半球之间的连接，以及它们在正常发育过程和对损伤的响应过程中，它们在电路可塑性和成熟中的作用。这些连接知之甚少，它们对电路发展的贡献和可塑性尚不清楚。视神经底面与哺乳动物上丘同源，对于从多种方式处理感觉信息至关重要。这些内直肠输入是直肠神经元，它们在对侧半球中延伸轴突延伸到连合术的轴突，以使其突触到直肠神经元上。在上丘中，已经提出了这些输入 介导相互抑制；但是，该功能的基础机制和电路级机制尚不清楚。我们已经开发了一种新的解剖准备，以使我们能够专门探索1）直肠内输入如何在Xenopus中发展出来，以及这些输入如何促进电路形成，2）直肠内输入强度的变化如何影响视网膜直肠电路的形成和可变性以及可变性以及3）对这些输入的重塑，以及他们的贡献，以及他们的贡献，以及他们回收的贡献。这些实验不仅将解决有关神经回路如何形成和维护的基本问题，而且还将提供有关突触连通性破坏的疾病状态中发生的变化的关键信息，例如精神分裂症，中风和脑损伤。