Abstract：
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.
摘要：
越来越多的证据表明，神经肽信号传导会影响听觉计算。我们先前表明，神经肽Y（NPY）在下丘（IC）中由GABA能星状神经元群表达，并且NPY调节IC中局部兴奋回路的强度。最初使用NPY-hrGFP小鼠表征NPY神经元，其中人源化海肾绿荧光蛋白（hrGFP）表达表明NPY表达在测定时，即，表达式跟踪方法。然而,在其他大脑区域的研究表明，NPY表达可以根据几个因素而变化，这表明NPY-hrGFP小鼠可能会错过在实验日期不表达NPY的NPY神经元。这里,我们假设具有NPY表达能力的神经元代表了比以前报道的更大的ICGABA能神经元群体。为了检验这个假设，我们使用谱系追踪方法对在实验日期之前的任何时间点表达NPY的神经元进行不可逆标记.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先前的数据集进行了比较，揭示了比以前发现的更多的NPY神经元。此外,我们使用光遗传学测试NPY神经元的局部连通性,发现NPY神经元通常向同侧IC中的其他神经元提供抑制性突触输入.一起,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中动态调节，并提供NPY神经元在IC中形成局部抑制回路的功能证据。
