Mechanisms of neuron excitability for vocalizations in songbirds

鸣禽发声神经元兴奋机制

• 批准号: 2154646
• 负责人: Henrique von Gersdorff
• 金额: $ 140万
• 依托单位: Oregon Health & Science University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154646&HistoricalAwards=false
• 关键词: Mechanisms; neuron; excitability; vocalizations; songbirds

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.

要了解大脑如何控制精细的运动技能，如弹钢琴或发出声音(如歌曲)，需要了解脑细胞的电特性是如何受到调节的。像斑马雀这样的鸣鸟，是理解大脑如何控制与歌曲产生有关的精细运动技能的优秀物种，因为幼年鸣鸟是通过模仿成年鸣鸟来学习唱歌的。参与这种模仿学习的大脑回路已经被研究了几十年，现在已经被很好地描述了。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特性，来了解这些研究充分的大脑区域内的电特性。这些研究的目标是测量这些细胞的精确电活动，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尖端的分子和细胞神经科学。学生将通过参加夏季股票和神经科学项目、向美洲原住民社区发表演讲以及参加以少数群体为重点的会议来招收，重点是代表人数较少的少数族裔，包括拉丁美洲的实习生。我们的工作成果将通过出版物、科学会议上的演讲、科学博览会和大脑意识活动来公布。我们建议研究神经元的内在可兴奋特性是如何在大脑电路中调节的，这有助于复杂的学习行为。我们将使用斑马雀，这是一种具有良好发声回路特征的鸣禽物种，并将重点放在RA核(大脑皮层粗壮核)上，这是一个类似于哺乳动物上皮质发声运动神经元的运动皮质区域。我们最近发现，高阈值电压门控性钾通道(KV3.1)在RA中有不同的表达，并且在表达上经历了显著的发育“开关”，与RA神经元兴奋特性的显著年龄差异相一致。我们推测，这些分子和细胞的变化在形成RA的兴奋性特性和建立成人RA的特征(例如，高激发频率和保真度)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的生物声学特征是重要的。我们将使用脑片的全细胞膜片钳记录、原位杂交和SONG生物声学分析，以及基于病毒的操作和动态钳制模型来测试这些假设，以机械地测试特定的关键离子通道亚单位在调节RA投射神经元非常狭窄的动作电位中的作用。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Motor cortex analogue neurons in songbirds utilize Kv3 channels to generate ultranarrow spikes.

• DOI: 10.7554/elife.81992
• 发表时间: 2023-05-09
• 期刊: eLife
• 影响因子: 7.7
• 作者: Zemel BM;Nevue AA;Tavares LES;Dagostin A;Lovell PV;Jin DZ;Mello CV;von Gersdorff H
• 通讯作者: von Gersdorff H