Lineage-tracing reveals an expanded population of NPY neurons in the inferior colliculus.
Lineage-tracing reveals an expanded population of NPY neurons in the inferior colliculus.
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谱系追踪揭示了下丘中 NPY 神经元数量的增加。
DOI：
10.1101/2024.03.27.587042
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Roberts,MichaelT
中科院分区：
文献类型：
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作者：
Silveira,MarinaA;Herrera,YoaniN;Beebe,NicholeL;Schofield,BrettR;Roberts,MichaelT
越来越多的证据表明，神经肽信号塑造听觉计算。我们以前的研究表明，神经肽Y（NPY）在下丘（IC）的GABA能星状神经元的人口表达和NPY调节的强度，在IC的局部兴奋回路。最初使用NPY-hrGFP小鼠表征NPY神经元，其中人源化海肾绿色荧光蛋白（hrGFP）表达指示在测定时的NPY表达，即，一种表情追踪方法然而，在其他脑区域的研究表明，NPY表达可以基于几个因素而变化，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。在这里，我们假设有能力表达NPY的神经元代表了比以前报道的更大的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的任何时间点表达NPY的神经元。然后，我们将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，揭示了比以前发现的更多的NPY神经元。此外，我们使用光遗传学来测试NPY神经元的局部连接，发现NPY神经元向同侧IC中的其他神经元提供抑制性突触输入。总之，我们的数据扩展了定义的神经肽Y神经元的IC，表明，神经肽Y的表达可能是动态调节的IC，并提供功能的证据表明，神经肽Y神经元形成局部抑制电路的IC。新&值得注意的是在整个大脑区域，神经肽Y（NPY）的表达是动态的，并受外在和内在因素的影响。我们以前表明，NPY是由一类在听觉中脑的抑制神经元表达。在这里，我们发现，这类神经元还包括以前表达NPY的神经元，这表明NPY的表达是动态调节听觉中脑。我们还提供了功能的证据，神经肽Y神经元有助于在听觉中脑的局部抑制回路。
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 & NOTEWORTHYAcross 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.