Mechanisms Underlying Rhythm Generation in Identified Spinal Interneurons in Mice

小鼠脊髓中间神经元节律产生的机制

• 批准号: 7409038
• 负责人: Lea Ziskind-Conhaim
• 金额: $ 28.26万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7409038
• 关键词: Action Potentials; Adolescent; Agonist; Area; Behavior; Bilateral; Biological Neural Networks; Characteristics; Chromosome Pairing; Contralateral; Electric Stimulation; Embryo; Engineering; Enzymes; Feedback; Fire - disasters; GAD67 enzyme; Gene Expression; Generations; Genes; Glutamate Decarboxylase; Glutamates; Green Fluorescent Proteins; Hindlimb; Homeodomain Proteins; In Vitro; Intention; Interneurons; Ipsilateral; Knowledge; Left; Locomotion; Medial; Mediating; Membrane; Motor; Motor Activity; Motor Neurons; Motor output; Movement; Mus; Neurons; Patients; Pattern; Peripheral; Phase; Population; Procedures; Process; Property; Proteins; Reporter Genes; Research Personnel; Sensory; Side; Spinal; Spinal Cord; Spinal cord injury; Stimulus; Suid Herpesvirus 1; Swimming; Synapses; Testing; Therapeutic; Transgenic Mice; Vertebrates; Walking; base; central pattern generator; channel blockers; design; gamma-Aminobutyric Acid; in vivo; insight; neurotransmitter agonist; postnatal; postsynaptic; research study; response; voltage; voltage gated channel

DESCRIPTION (provided by applicant): The autonomous spinal networks that generate movements in vertebrates are referred to as central pattern generators (CPGs). The principal neurons in the locomotor circuitry include ipsilateral rhythmogenic interneurons, (rhythm generators), commissural interneurons that coordinate the rhythms between the left-right sides of the spinal cord (rhythm coordinators) and motoneurons. The integrated activity of these neuronal populations produces rhythmic excitation of motoneurons during hindlimb movements in walking vertebrates. The primary challenge in studying the cellular and synaptic mechanisms underlying rhythm generation in the locomotor circuitry is the identification of interneuronal populations that comprised integral components of rhythm-generating and rhythm-coordinating networks. To overcome some of the technical difficulties identifying locomotor-related interneurons in the isolated spinal cord, transgenic mice have been used with the intention of characterizing interneuronal populations based on their unique gene expression. Recent studies have documented that ventral neurons can be divided into five domains of specific genes that represent physiologically distinct neuronal populations with defined functions in motor behavior. .Such genes have been widely used to express the reporter gene green fluorescent protein (GFP), giving rise to visually identified neurons that can be targeted for repeated electrophysiological, morphological and immunohistochemical studies. In this proposal two lines of GFP positive transgenic mice will be used to study the mechanisms of rhythm generation in ipsilateral excitatory interneurons expressing the HB9 protein, and inhibitory commissural interneurons that synthesize the enzyme GAD67. The objectives of this proposal are: (1) to test the hypothesis that the Hb9 and GAD67 interneurons are integrated in rhythm-generating and rhythm- coordinating networks, respectively and (2) to test the hypothesis that different synaptic and cellular mechanisms underlie rhythm generation in these interneurons that perform different functions in the locomotor circuitry. Understanding the mechanisms that modulate the patterns of locomotion rhythms in functionally identified interneurons in the isolated spinal cord that is disconnected from descending voluntary control, will provide important insight into possible therapeutic strategies of activating undamaged neurons in rhythm generating networks of patients with spinal cord injuries.

描述（由申请人提供）：在脊椎动物中生成运动的自主脊柱网络称为中央模式发生器（CPGS）。运动电路中的主要神经元包括同侧节律性中间神经元（节奏发电机），连合神经元，它们在脊髓（节奏坐标剂）和运动神经元之间协调节奏。这些神经元种群的综合活性在行走脊椎动物的后肢运动过程中会产生运动神经元的节奏激发。研究运动电路中节奏产生的细胞和突触机制的主要挑战是鉴定了神经元种群，这些神经元种群包括节奏生成节奏和节奏协调网络的积分成分。为了克服某些技术困难，鉴定与运动相关的脊髓中的运动相关中间神经元，已使用转基因小鼠，目的是根据其独特的基因表达来表征神经元群体。最近的研究表明，腹神经元可以分为特定基因的五个领域，这些基因代表了生理上不同的神经元种群，在运动行为中具有定义的功能。 。类似基因已被广泛用于表达报告基因绿色荧光蛋白（GFP），从而引起了视觉上鉴定的神经元，这些神经元可以针对重复的电生理，形态学和免疫组织化学研究。在该提案中，将使用两条GFP阳性转基因小鼠来研究表达HB9蛋白的同侧兴奋性中间神经元中节奏产生的机制，以及抑制性的合并中间神经元合成酶GAD67。该提案的目的是：（1）检验以下假设：HB9和GAD67中间神经元分别集成在节奏生成和节奏的网络中，以及（2）测试以不同的Synaptic和细胞机制在这些界面中产生不同函数中不同函数的混合和细胞机制的假设，这些机制在不同的interneurons中发挥了不同的作用。了解在孤立的脊髓功能性识别的中间神经元中调节运动性节奏模式的机制，这些脊髓中的神经元与降落自愿控制脱节的机制将为激活脊柱损伤患者的节奏产生网络中未经损害的神经元的可能治疗策略提供重要的见解。