Incorporation of newborn neurons in vocal learning

我们提出了一个新的研究计划，我们的目标是了解神经元的多样性， 在成年鸣禽的大脑中产生。鸣禽是唯一增加新神经元的温血脊椎动物 到明确定义的运动回路，这些运动回路是控制一种容易量化的行为，鸟鸣的基础。成年男性 斑胸草雀--它们学会唱一种高度可重复的歌，并在一生中不断地保持这种歌声 产生成人出生的神经元，这些神经元被纳入起源于HVC的发声运动通路， 感觉运动区是歌曲产生的基础。HVC中的一类神经元投射到RA（HVCRA）， 发声运动通路的一部分，在成年期持续产生，并在歌曲产生中活跃。 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 然而，我们对它们从成神经细胞到分化的神经元的功能成熟知之甚少。 我们的第一个假设是，成熟HVCRA神经元的稀疏和精确的放电模式是从一个特定的神经元发展而来的。 更易兴奋的电生理学，由于钾电导增加而变得更受抑制， 抑制性突触输入。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，并随后记录他们的发展，不成熟的电生理在脑切片。我们可以 然后将它们与成熟的HVCRA神经元进行比较，以观察这些神经元在其发育过程中的变化。 成熟有趣的是，HVCRA神经元仅占所有成年HVC神经元的约50%。这些 其余未鉴定的成人HVC神经元不是RA投射，也不是局部抑制性的 中间神经元我们实验室的初步数据表明，这些未经鉴定的神经元瞬时表达 DARPP-32是多巴胺感受神经元的标志物，并且不投射到RA。第二个假设是， HVC中的DARPP-32+成人出生神经元包括一个独特的局部兴奋性中间神经元群体， DA在这些成年出生的RA的发育和调节中起短暂的作用， 神经元这项研究是创新的，因为它试图确定一个以前未知的成年出生人口 神经元在一个其他定义明确和广泛研究的大脑区域，可以说是最好的 研究的声乐学习模式可用。了解所有成人出生的神经元在HVC中的功能作用 将提高我们对神经元回路如何改善和保持行为精确性的理解， 稳定

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.