Silveira Marina A, Herrera Yoani N, Beebe Nichole L, Schofield Brett R, Roberts Michael T
Kresge Hearing Research Institute, Department of Otolaryngology - Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan.
Department of Neuroscience, Development and Regenerative Biology, The University of Texas at San Antonio, San Antonio, Texas.
bioRxiv. 2024 Mar 30:2024.03.27.587042. doi: 10.1101/2024.03.27.587042.
Growing evidence suggests that neuropeptide signaling shapes auditory computations. We previously showed that neuropeptide Y (NPY) is expressed in the inferior colliculus (IC) by a population of GABAergic stellate neurons and that NPY regulates the strength of local excitatory circuits in the IC. NPY neurons were initially characterized using the NPY-hrGFP reporter mouse, in which hrGFP expression indicates NPY expression at the time of assay, i.e., an expression-tracking approach. However, studies in other brain regions have shown that NPY expression can vary based on a range of factors, suggesting that the NPY-hrGFP mouse might miss NPY neurons not expressing NPY proximal to the experiment date. Here, we hypothesized that neurons with the ability to express NPY represent a larger population of IC GABAergic neurons than previously reported. To test this hypothesis, we used a lineage-tracing approach to irreversibly tag neurons that expressed NPY at any point prior to the experiment date. We then compared the physiological and anatomical features of neurons labeled with this lineage-tracing approach to our prior data set, revealing a larger population of NPY neurons than previously found. In addition, we used optogenetics to test the local connectivity of NPY neurons and found that NPY neurons routinely provide inhibitory synaptic input to other neurons in the ipsilateral IC. Together, our data expand the definition of NPY neurons in the IC, suggest that NPY expression might be dynamically regulated in the IC, and provide functional evidence that NPY neurons form local inhibitory circuits in the IC.
越来越多的证据表明，神经肽信号传导塑造了听觉计算。我们之前表明，神经肽Y（NPY）在下丘（IC）中由一群GABA能星状神经元表达，并且NPY调节IC中局部兴奋性回路的强度。NPY神经元最初是使用NPY-hrGFP报告基因小鼠进行表征的，其中hrGFP表达在检测时表明NPY表达，即一种表达追踪方法。然而，在其他脑区的研究表明，NPY表达可能会因一系列因素而有所不同，这表明NPY-hrGFP小鼠可能会遗漏在实验日期临近时不表达NPY的NPY神经元。在这里，我们假设能够表达NPY的神经元代表了比先前报道的更大的IC GABA能神经元群体。为了验证这一假设，我们使用了谱系追踪方法来不可逆地标记在实验日期之前任何时间表达NPY的神经元。然后，我们将用这种谱系追踪方法标记的神经元的生理和解剖特征与我们之前的数据集进行比较，发现NPY神经元的群体比之前发现的更大。此外，我们使用光遗传学来测试NPY神经元的局部连接性，发现NPY神经元通常会向同侧IC中的其他神经元提供抑制性突触输入。总之，我们的数据扩展了IC中NPY神经元的定义，表明NPY表达可能在IC中受到动态调节，并提供了功能证据表明NPY神经元在IC中形成局部抑制性回路。
