Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109.
Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, Ohio 44272.
J Neurosci. 2020 Jun 10;40(24):4685-4699. doi: 10.1523/JNEUROSCI.0420-20.2020. Epub 2020 May 6.
Located in the midbrain, the inferior colliculus (IC) integrates information from numerous auditory nuclei and is an important hub for sound processing. Despite its importance, little is known about the molecular identity and functional roles of defined neuron types in the IC. Using a multifaceted approach in mice of both sexes, we found that neuropeptide Y (NPY) expression identifies a major class of inhibitory neurons, accounting for approximately one-third of GABAergic neurons in the IC. Retrograde tracing showed that NPY neurons are principal neurons that can project to the medial geniculate nucleus. In brain slice recordings, many NPY neurons fired spontaneously, suggesting that NPY neurons may drive tonic inhibition onto postsynaptic targets. Morphologic reconstructions showed that NPY neurons are stellate cells, and the dendrites of NPY neurons in the tonotopically organized central nucleus of the IC cross isofrequency laminae. Immunostaining confirmed that NPY neurons express NPY, and we therefore hypothesized that NPY signaling regulates activity in the IC. In crosses between and Ai14 Cre-reporter mice, we found that NPY Y receptor (YR)-expressing neurons are glutamatergic and were broadly distributed throughout the rostrocaudal extent of the IC. In whole-cell recordings, application of a high-affinity YR agonist led to hyperpolarization in most YR-expressing IC neurons. Thus, NPY neurons represent a novel class of inhibitory principal neurons that are well poised to use GABAergic and NPY signaling to regulate the excitability of circuits in the IC and auditory thalamus. The identification of neuron types is a fundamental question in neuroscience. In the inferior colliculus (IC), the hub of the central auditory pathway, molecular markers for distinct classes of inhibitory neurons have remained unknown. We found that neuropeptide Y (NPY) expression identifies a class of GABAergic principal neurons that constitute one-third of the inhibitory neurons in the IC. NPY neurons fire spontaneously, have a stellate morphology, and project to the auditory thalamus. Additionally, we found that NPY signaling hyperpolarized the membrane potential of a subset of excitatory IC neurons that express the NPY Y receptor. Thus, NPY neurons are a novel class of inhibitory neurons that use GABA and NPY signaling to regulate activity in the IC and auditory thalamus.
位于中脑的下丘（IC）整合了来自许多听觉核的信息，是声音处理的重要枢纽。尽管其重要性不言而喻，但对于 IC 中特定神经元类型的分子特征和功能作用却知之甚少。本研究在雌雄小鼠中采用多方面的方法，发现神经肽 Y（NPY）表达可鉴定出一大类抑制性神经元，约占 IC 中 GABA 能神经元的三分之一。逆行追踪显示，NPY 神经元是可以投射到内侧膝状体核的主要神经元。在脑片记录中，许多 NPY 神经元自发放电，表明 NPY 神经元可能驱动突触后靶标上的紧张性抑制。形态重建显示，NPY 神经元为星型细胞，并且在具有音调组织的中央核中，NPY 神经元的树突跨越等频层。免疫染色证实 NPY 神经元表达 NPY，因此我们假设 NPY 信号调节 IC 中的活动。在 和 Ai14 Cre 报告小鼠之间的杂交中，我们发现 NPY Y 受体（YR）表达神经元为谷氨酸能神经元，并且广泛分布于 IC 的前后延伸范围内。在全细胞记录中，高亲和力 YR 激动剂的应用导致大多数 YR 表达的 IC 神经元超极化。因此，NPY 神经元代表一类新型抑制性主要神经元，它们具有使用 GABA 能和 NPY 信号来调节 IC 和听觉丘脑回路兴奋性的潜力。神经元类型的鉴定是神经科学的一个基本问题。在下丘（IC），即中枢听觉通路的枢纽，用于不同类别的抑制性神经元的分子标记仍然未知。我们发现，神经肽 Y（NPY）表达可鉴定出一类 GABA 能主要神经元，占 IC 中抑制性神经元的三分之一。NPY 神经元自发放电，具有星型形态，并投射到听觉丘脑。此外，我们发现 NPY 信号使表达 NPY Y 受体的兴奋性 IC 神经元亚群的膜电位超极化。因此，NPY 神经元是一类新型的抑制性神经元，它们利用 GABA 和 NPY 信号来调节 IC 和听觉丘脑的活动。
