Synaptic and circuit mechanisms of learned vocal production

学习性发声的突触和电路机制

• 批准号: 8668638
• 负责人: MICHAEL A LONG
• 金额: $ 32.85万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-11 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8668638
• 关键词: Address; Adolescent; Animals; Area; Behavior; Behavioral; Cell Nucleus; Cell Size; Communication; Communication impairment; Complex; Devices; Disease; Elements; Event; Exhibits; Experimental Designs; Fees; Functional disorder; Generations; Gold; Human; Individual; Intracellular Membranes; Learning; Link; Measures; Mediating; Membrane Potentials; Methods; Modeling; Motor; N-Methylaspartate; Neocortex; Neurons; Neurosciences; Noise; Pathology; Pattern; Play; Population; Positioning Attribute; Process; Production; Property; Relative (related person); Rest; Role; Sensory; Songbirds; Speech; Speed; Stereotyping; Structure; Synapses; System; Technology; Testing; Therapeutic; Time; Toddler; Vertebrates; base; bird song; design; extracellular; insight; instrument; motor control; motor learning; neural circuit; neuromechanism; research study; sensory feedback; tool; vocal learning; vocalization; zebra finch

A principle aim of the field of neuroscience is the study of the mechanisms which enable learned complex behaviors, such as speaking or playing an instrument. However, the processes which underlie the generation of these behavioral sequences are poorly understood, in part because of the limitations of available methods for measuring neuronal activity in behaving animals. Recently, we designed and built a new experimental tool that enables the first ever intracellular recordings in freely behaving small animals engaged in complex behaviors. These recordings provide a wealth of information that is not available with extracellular recordings and allow for the testing of previously unapproachable hypotheses concerning the mechanisms of neural sequence generation in freely behaving animals. To that end, the experiments within this proposal focus on an important motor control nucleus in the zebra finch called HVC (formerly known as the high vocal center), which is analogous to motor areas of the mammalian neocortex. We have previously shown that HVC acts as a 'clock' for the production of learned vocalizations, but we understand little about the mechanisms by which this circuit operates. Experiments described in the first specific aim test the competing hypotheses that neurons within HVC are sequentially activated either through their intrinsic properties or through overt synaptic connections within that nucleus. The second specific aim will identify the relative impact of excitatory and inhibitory synaptic inputs on sequence generation. The third specific aim will directly address an existing controversy concerning the role of sensory feedback on motor patterning within HVC. Through these experiments, we will generate fundamental insights into the processes involved in the production of learned motor sequences in order to inform therapeutic approaches for a range of relevant disorders.

神经科学领域的主要目的是研究该机制，这些机制能够使学习的复杂行为（例如说话或演奏乐器）。但是，这些行为序列产生的过程的理解很少，部分原因是可用方法的局限性用于测量行为动物的神经元活性。最近，我们设计并构建了一种新的实验工具，该工具可以在自由地行为从事复杂行为的小动物中的第一个细胞内记录。这些记录提供了大量的信息，这些信息无法带有细胞外记录，并允许测试以前不可接受的假设，即关于自由表现的动物的神经序列产生的机制。为此，该提案中的实验集中在称为HVC（以前称为高声带）的斑马雀科中重要的运动控制核，该核与哺乳动物新皮层的运动区域类似。我们先前已经表明，HVC充当了学习发声的“时钟”，但我们对该电路运行的机制知之甚少。在第一个特定目标中描述的实验测试了竞争假设，即HVC中的神经元通过其内在特性或通过该核中的公开突触连接而被依次激活。第二个特定目的将确定兴奋性和抑制性突触输入对序列产生的相对影响。第三个特定目标将直接解决有关HVC内部运动构图的作用的现有争议。通过这些实验，我们将对学习的运动序列的生产过程产生基本见解，以便为一系列相关疾病的治疗方法提供信息。