Incorporation of newborn neurons in vocal learning

将新生神经元纳入发声学习

基本信息

批准号：
10292179
负责人：
Gloster Aaron
金额：
$ 48.93万
依托单位：
WESLEYAN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10292179
关键词：
Acute Address Adult Axon Behavior Behavioral Blood Brain Brain region Cell Nucleus Cells Complex DARPP Data Development Dopamine Electrophysiology (science)Exhibits Gene Expression Human Immediate-Early Genes Immunohistochemistry Interneurons Label Laboratories Learning Life Maintenance Measures Membrane Membrane Potentials Memory Mental Depression Methods Mitosis Modeling Motor Motor Pathways Neuromodulator Neurons Pathway interactions Pattern Phosphoproteins Physiology Play Population Potassium Production Property Reproducibility Research Resistance Rest Role Signal Transduction Slice Songbirds Study models Synapses System Testing Tissue Fixation Vertebrates adult neurogenesis bird song improved innovation male motor behavior neuroblast neurogenesis neuronal circuitry neurophysiology newborn neuron novel patch clamp programs relating to nervous system response vocal learning voltage clamp young adult zebra finch

项目摘要

We propose a novel research program in which we aim to understand the diversity of neurons that are produced in the adult songbird brain. Songbirds are the only warm-blooded vertebrates that add new neurons to well-defined motor circuits underlying the control of an easily quantifiable behavior, birdsong. Adult male zebra finches – which learn to sing a highly reproducible song and maintain it throughout life – continually produce adult-born neurons that are incorporated into the vocal motor pathway originating in HVC, the sensorimotor region that underlies the song production. One class of neurons in HVC project to RA (HVCRA) as part of the vocal motor pathway, are continually produced in adulthood, and are active in song production. Mature HVCRA neurons have uniquely sparse and temporally precise firing properties that underlie song stability, and yet we know very little about their functional maturation from neuroblast to differentiated neuron. Our first hypothesis is that the sparse and precise firing pattern of mature HVCRA neurons develops from a more excitable electrophysiology that becomes more restrained due to increased potassium conductances and inhibitory synaptic inputs. We will accomplish this by using a retroviral approach to fluorescently label adult born neurons and subsequently record their developing, immature electrophysiology in brain slices. We can then compare them to mature HVCRA neurons to see how these neurons change over the course of their maturation. Interestingly, HVCRA neurons only constitute about 50% of all adult-born HVC neurons. These remaining unidentified adult-born HVC neurons are not RA-projecting, nor are they local inhibitory interneurons. Preliminary data from our laboratory suggests that these unidentified neurons transiently express DARPP-32, a marker of dopaminoceptive neurons, and do not project to RA. Our second hypothesis is that DARPP-32+ adult born neurons in HVC comprise a unique population of local excitatory interneurons that do not project to RA, and that DA plays a transient role in the development and modulation of these adult-born neurons. This study is innovative because it seeks to identify a previously unknown population of adult born neurons in an otherwise well-defined and widely-studied brain region that has served as arguably the best studied model of vocal learning available. Understanding the functional roles of all adult born neurons in HVC will improve our understanding of how neuronal circuits improve and maintain behavioral precision and stability.

我们提出了一项新颖的研究计划，旨在了解神经元的多样性鸣禽是唯一能增加新神经元的温血脊椎动物。明确的运动回路控制着一种容易量化的行为，即成年雄性鸟鸣。斑胸草雀——学会唱出高度可重复的歌曲，并终生保持这种歌曲——不断地产生成年出生的神经元，这些神经元被整合到起源于 HVC 的发声运动通路中， HVC 中的一类神经元投射到 RA (HVCRA) 作为歌曲产生的基础。声音运动通路的一部分，在成年期持续产生，并活跃于歌曲创作中。成熟的 HVCRA 神经元具有独特的稀疏和时间精确的放电特性，这是歌曲的基础稳定性，但我们对它们从神经母细胞到分化神经元的功能成熟知之甚少。我们的第一个假设是，成熟 HVCRA 神经元稀疏而精确的放电模式是从更兴奋的电生理学由于钾电导的增加而变得更加受到抑制我们将通过使用逆转录病毒方法荧光标记成人来实现这一目标。出生的神经元，然后在脑切片中记录它们发育中的、不成熟的电生理学。然后将它们与成熟的 HVCRA 神经元进行比较，看看这些神经元在其生命过程中如何变化提示，HVCRA 神经元仅占所有成年 HVC 神经元的约 50%。剩余的未识别的成年 HVC 神经元不是 RA 投射的，也不是局部抑制的我们实验室的初步数据表明这些未识别的神经元短暂表达。 DARPP-32 是多巴胺感受神经元的标记物，不会投射到 RA 我们的第二个假设是： HVC 中的 DARPP-32+ 成年神经元包含一组独特的局部兴奋性中间神经元，不投射到 RA，并且 DA 在这些成人出生的发育和调节中起着短暂的作用这项研究具有创新性，因为它旨在识别以前未知的成年出生群体。神经元位于一个定义明确且经过广泛研究的大脑区域，该区域一直是有争议的最佳神经元研究了现有的声音学习模型，了解所有成年神经元在 HVC 中的功能作用。将提高我们对神经回路如何改善和保持行为精确度的理解稳定。