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.

神经科学领域的一个主要目标是研究能够学习复杂行为的机制，例如说话或演奏乐器。然而，这些行为序列产生的基础过程知之甚少，部分原因是测量行为动物神经元活动的可用方法的局限性。最近，我们设计并构建了一种新的实验工具，该工具首次在从事复杂行为的自由行为小动物中进行细胞内记录。这些记录提供了丰富的信息，是不可用的细胞外记录，并允许测试以前无法接近的假设有关的机制，神经序列生成在自由行为的动物。为此，该提案中的实验集中在斑胸草雀中一个重要的运动控制核团，称为HVC（以前称为高音中心），它类似于哺乳动物新皮层的运动区域。我们以前已经表明，HVC作为一个“时钟”的生产学习发声，但我们了解这个电路的运作机制很少。在第一个具体目标中描述的实验测试了HVC内的神经元通过其内在特性或通过该核内的明显突触连接被顺序激活的竞争性假设。第二个具体目标将确定兴奋性和抑制性突触输入对序列生成的相对影响。第三个具体的目标将直接解决现有的争议的作用，感觉反馈的运动模式内HVC。通过这些实验，我们将对学习运动序列的产生过程产生基本的见解，以便为一系列相关疾病的治疗方法提供信息。