Mechanisms of neuron excitability for vocalizations in songbirds

要了解大脑如何控制诸如弹钢琴或唱歌等精细运动技能，就需要了解脑细胞的电特性是如何被调节的。鸣禽，如斑胸草雀，是了解大脑如何控制与鸣叫有关的精细运动技能的绝佳物种，因为幼年鸣禽通过模仿成年鸣禽来学习鸣叫。参与这种模仿学习的大脑回路已经被研究了几十年，现在已经得到了很好的描述。该项目旨在通过关注这些区域的细胞，以及离子如何进出这些细胞的通道来产生电学特性，从而了解这些已被充分研究过的大脑区域的电学特性。这些研究的目标是精确测量这些细胞的电活动，并修改这些细胞中可能影响电特性的基因，从而可能影响歌曲产生过程中的运动模式。这些研究将使本科生和高中生接触到最前沿的分子和细胞神经科学。招收学生时，将通过参加暑期公平和神经科学项目、向美洲土著社区作报告以及参加以少数族裔为重点的会议，重点关注包括拉丁美洲学员在内的代表性不足的少数族裔。我们的工作成果将通过出版物、科学会议、科学博览会和大脑意识活动的演讲获得。我们建议研究神经元的内在可兴奋特性是如何在大脑回路中调节的，而大脑回路是为复杂的学习行为提供支持的。我们将以斑马雀为研究对象，这是一种具有良好发声回路特征的鸣禽，并将重点放在RA核（robustus arcopallialis）上，这是一个类似于哺乳动物上皮层声带运动神经元的运动皮质区域。我们最近发现，高阈值电压门控钾通道（Kv3.1）在RA中有差异表达，并且在表达上经历了显著的发育“开关”，这与RA神经元的可兴奋性的显著年龄差异相一致。我们假设这些分子和细胞的变化在塑造RA的兴奋性特性和建立成人RA的特征（例如高放电率和保真度）方面发挥了关键作用，这些特征对于在声音习得的关键时期出现的歌曲生物声学特征很重要。我们将使用脑切片全细胞膜片钳记录，原位杂交，歌曲生物声学分析，以及基于病毒的操作和动态钳建模来验证这些假设，以机械地测试特定关键离子通道亚基在调节RA投射神经元显着狭窄的动作电位中的作用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Understanding how the brain controls fine motor skills such as playing the piano or producing vocalizations such as song requires knowing how electrical properties of brain cells are regulated. Songbirds, like the zebra finch, are excellent species for understanding how the brain controls fine motor skills involved in song production because the juvenile songbird learns to sing its species songs by imitating an adult of its species. The brain circuits involved in this imitative learning have been studied for many decades and are now well described. The project is aimed at understanding the electrical properties within these well-studied brain regions by focusing on the cells in these areas and how ions move in and out of channels in these cells to produce electrical properties. The goal of these studies is to measure precise electrical activity of these cells and to modify genes in these cells that may influence electrical properties thereby possibly affecting motor patterns during song production. These studies will expose undergraduate and high school students to cutting edge molecular and cellular neuroscience. Students will be recruited with a major emphasis on underrepresented minorities, including Latin-American trainees, through participation in a Summer Equity and Neuroscience Programs, presentations to Native American communities, and participation in minority-focused meetings. The results of our work will be available through publications, presentations at scientific conferences, science fairs and Brain Awareness events. We propose to study how intrinsic excitable properties of neurons are modulated within the brain circuitry that subserves a complex learned behavior. We will use zebra finches, a songbird species with a well characterized vocal circuitry, and focus on nucleus RA (robustus arcopallialis), a motor cortical area analogous to upper cortical vocal motor neurons in mammals. We have recently found that high-threshold voltage gated potassium channels (Kv3.1) are differentially expressed in RA and undergo marked developmental “switches” in expression, in concert with marked age differences in the excitable properties of RA neurons. We hypothesize that these molecular and cellular changes play key roles in shaping RA’s excitability properties and establishing features of adult RA (e.g. high firing rates and fidelity) that are important for the emerging bioacoustic features of song during the critical period for vocal acquisition. We will test these hypotheses using whole-cell patch clamp recordings in brain slices, in situ hybridization, and song bioacoustics analysis, as well as viral-based manipulations and dynamic clamp modeling to mechanistically test the role of specific key ion channel subunits in modulating the remarkably narrow action potentials of RA projection neurons.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.