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Defining a thalamic role in premotor cortical sequence generation

定义丘脑在运动前皮质序列生成中的作用

基本信息

批准号：
10259673
负责人：
Margot Elmaleh
金额：
$ 4.01万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2022-07-31
项目状态：
已结题

项目摘要

PROJECT SUMMARY Sequential neural activity is ubiquitous throughout the brain and is thought to underly many essential processes from working memory to complex motor behavior. However, the mechanisms of sequence generation still remain unknown; whether neural sequences are generated locally or emerge from the cooperation between local circuits and long-range inputs is controversial. For example, input from thalamic regions has been shown to be involved in the sequential activity that occurs in cortex during skilled motor acts. The adult male zebra finch provides an ideal system to investigate mechanisms of cortical sequence generation. After learning his courtship song through months of extensive practice as a juvenile, the zebra finch produces a stereotyped song composed of repeated complex vocal elements known as syllables. Proper song production requires the coordinated action of multiple nuclei across the song-production network, including two cortical regions, HVC (proper name) and the robust nucleus of the arcopallium (RA) and the thalamic nucleus uvaeformis (Uva). While lesion studies have shown the importance of Uva to song production, the role of these thalamic inputs in facilitating the sequential activity in HVC and RA is still unclear. In this proposal, I will test three models of sequence generation in the zebra finch song-production network, each of which attributes a different role to the thalamus in shaping cortical sequences. In model 1, thalamic input is required for moment-to-moment progression through the cortical sequence. In model 2, thalamic input is necessary to link discrete cortical sequences encoding individual syllables. In model 3, the thalamus acts to orchestrate progression through a continuous cortical sequence that encodes the entire song. Previous studies have sought to distinguish between these models by assessing the behavioral impact of lesioning Uva. Lesions eliminate singing behavior, thus precluding any opportunity to study the circuit. However, sleep provides the opportunity to probe this circuit, where song-like `replay' fragments have been observed in individual cortical neurons and neuron pairs without subsequent vocalizations. I will first adapt high-density silicon probe technology for the zebra finch and build analytical tools to decode the song-content of sleep replay. Next I will investigate the role of thalamic input in cortical sequence generation by perturbing this input and determining the impact this perturbation has on cortical replay. In this way, I will uncover the role of thalamic input in cortical sequences underlying complex skilled behavior in the zebra finch. These experiments will increase our understanding of how thalamic inputs contribute to cortical dynamics in healthy networks and provide insight into pathological processes that disrupt these dynamics during disease.

项目总结顺序神经活动在整个大脑中无处不在，被认为是许多基本过程的不足。从工作记忆到复杂的运动行为。然而，序列生成的机制仍然存在未知；神经序列是局部产生的，还是局部回路之间的合作产生的而且，长期投入是有争议的。例如，来自丘脑区域的输入已被证明涉及到在熟练的运动动作期间，大脑皮质发生的顺序活动中。成年雄性斑马雀提供了一种研究皮层序列产生机制的理想系统。在学了他的求爱歌之后作为一个少年，经过几个月的广泛练习，斑马雀会产生一首刻板的歌曲，由被称为音节的重复的复杂的发音元素。正确的歌曲制作需要协调行动包括HVC(专有名称)和HVC(专有名称)两个大脑皮层区域粗壮的延髓核(RA)和丘脑葡萄状核(UVA)。虽然损伤研究已经显示了UVA对歌曲产生的重要性，这些丘脑输入在促进序列 HVC和RA的活性仍不清楚。在本提案中，我将测试三个序列生成模型斑马雀歌曲制作网络，每个网络都将不同的角色归因于丘脑在塑造大脑皮质中的作用序列。在模型1中，丘脑的输入是通过大脑皮层的瞬间到瞬间的推进所必需的。序列。在模型2中，丘脑输入是连接编码个体的离散皮质序列所必需的音节。在模型3中，丘脑通过一个连续的皮质序列来协调进程对整首歌进行编码。以前的研究试图通过评估损伤UVA的行为影响。病变消除了歌唱行为，从而排除了任何学习的机会巡回赛。然而，睡眠提供了探测这个回路的机会，在这个回路中，像歌曲一样的“重放”片段在单个皮质神经元和神经元对中观察到，没有随后的发声。我会先适应高密度硅探头技术用于斑马雀，并建立分析工具来解码歌曲内容睡眠重播。接下来，我将研究丘脑输入在皮层序列生成中的作用输入并确定此扰动对皮质回放的影响。通过这种方式，我将揭开斑马雀复杂熟练行为背后的皮层序列丘脑输入。这些实验将增加我们对丘脑输入如何有助于健康网络和大脑皮质动力学的理解洞察疾病期间扰乱这些动态的病理过程。