Marina A Silveira, Yoani N Herrera, Nichole L Beebe, Brett R Schofield, Michael T Roberts
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引用次数: 0
摘要
越来越多的证据表明,神经肽信号塑造了听觉计算。我们以前的研究表明,神经肽 Y(NPY)在下丘脑(IC)中由一群具有 GABA 能的星状神经元表达,NPY 可调节 IC 中局部兴奋回路的强度。NPY神经元最初是通过NPY-hrGFP小鼠来表征的,在这种小鼠中,人源化雷尼拉绿色荧光蛋白(hrGFP)的表达表示检测时NPY的表达,即表达追踪方法。然而,对其他脑区的研究表明,NPY的表达会因多种因素而变化,这表明NPY-hrGFP小鼠可能会错过在实验日期没有表达NPY的NPY神经元。在这里,我们假设具有表达 NPY 能力的神经元代表了比之前报道的更大的 IC GABA 能神经元群体。为了验证这一假设,我们采用了一种品系追踪方法,对在实验日期之前任何时候表达 NPY 的神经元进行了不可逆标记。然后,我们将用这种品系追踪方法标记的神经元的生理和解剖特征与之前的数据集进行了比较,结果发现NPY神经元的数量比之前发现的要多。此外,我们还使用光遗传学方法测试了 NPY 神经元的局部连通性,发现 NPY 神经元经常向同侧 IC 中的其他神经元提供抑制性突触输入。总之,我们的数据扩展了集成电路中 NPY 神经元的定义,表明集成电路中 NPY 的表达可能受到动态调节,并提供了 NPY 神经元在集成电路中形成局部抑制回路的功能性证据。
Lineage-tracing reveals an expanded population of NPY neurons in the inferior colliculus.
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 mouse, in which humanized renilla green fluorescent protein (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 several factors, suggesting that the NPY-hrGFP mouse might miss NPY neurons not expressing NPY on 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 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.NEW & NOTEWORTHY Across brain regions, neuropeptide Y (NPY) expression is dynamic and influenced by extrinsic and intrinsic factors. We previously showed that NPY is expressed by a class of inhibitory neurons in the auditory midbrain. Here, we find that this neuron class also includes neurons that previously expressed NPY, suggesting that NPY expression is dynamically regulated in the auditory midbrain. We also provide functional evidence that NPY neurons contribute to local inhibitory circuits in the auditory midbrain.
期刊介绍:
The Journal of Neurophysiology publishes original articles on the function of the nervous system. All levels of function are included, from the membrane and cell to systems and behavior. Experimental approaches include molecular neurobiology, cell culture and slice preparations, membrane physiology, developmental neurobiology, functional neuroanatomy, neurochemistry, neuropharmacology, systems electrophysiology, imaging and mapping techniques, and behavioral analysis. Experimental preparations may be invertebrate or vertebrate species, including humans. Theoretical studies are acceptable if they are tied closely to the interpretation of experimental data and elucidate principles of broad interest.