Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109
Kresge Hearing Research Institute, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan 48109.
J Neurosci. 2023 Nov 8;43(45):7626-7641. doi: 10.1523/JNEUROSCI.0900-23.2023. Epub 2023 Sep 13.
Neuropeptides play key roles in shaping the organization and function of neuronal circuits. In the inferior colliculus (IC), which is in the auditory midbrain, Neuropeptide Y (NPY) is expressed by a class of GABAergic neurons that project locally and outside the IC. Most neurons in the IC have local axon collaterals; however, the organization and function of local circuits in the IC remain unknown. We previously found that excitatory neurons in the IC can express the NPY Y receptor (YR) and application of the YR agonist, [Leu, Pro]-NPY (LP-NPY), decreases the excitability of YR neurons. As NPY signaling regulates recurrent excitation in other brain regions, we hypothesized that YR neurons form interconnected local circuits in the IC and that NPY decreases the strength of recurrent excitation in these circuits. To test this hypothesis, we used optogenetics to activate YR neurons in mice of both sexes while recording from other neurons in the ipsilateral IC. We found that nearly 80% of glutamatergic IC neurons express the Y receptor, providing extensive opportunities for NPY signaling to regulate local circuits. Additionally, YR neuron synapses exhibited modest short-term synaptic plasticity, suggesting that local excitatory circuits maintain their influence over computations during sustained stimuli. We further found that application of LP-NPY decreased recurrent excitation in the IC, suggesting that NPY signaling strongly regulates local circuit function in the auditory midbrain. Our findings show that YR excitatory neurons form interconnected local circuits in the IC, and their influence over local circuits is regulated by NPY signaling. Local networks play fundamental roles in shaping neuronal computations in the brain. The IC, localized in the auditory midbrain, plays an essential role in sound processing, but the organization of local circuits in the IC is largely unknown. Here, we show that IC neurons that express the Neuropeptide Y receptor (YR neurons) make up most of the excitatory neurons in the IC and form interconnected local circuits. Additionally, we found that NPY, which is a powerful neuromodulator known to shape neuronal activity in other brain regions, decreases the extensive recurrent excitation mediated by YR neurons in local IC circuits. Thus, our results suggest that local NPY signaling is a key regulator of auditory computations in the IC.
神经肽在塑造神经元回路的组织和功能方面发挥着关键作用。在下丘脑中，神经肽 Y (NPY) 由一类 GABA 能神经元表达，这些神经元投射到局部和下丘之外。下丘脑中的大多数神经元都有局部轴突分支；然而，下丘脑中局部回路的组织和功能仍不清楚。我们之前发现，下丘脑中的兴奋性神经元可以表达 NPY Y 受体 (YR)，应用 YR 激动剂 [Leu, Pro]-NPY (LP-NPY) 可以降低 YR 神经元的兴奋性。由于 NPY 信号调节其他脑区的回返兴奋，我们假设 YR 神经元在下丘脑中形成相互连接的局部回路，并且 NPY 降低这些回路中的回返兴奋强度。为了验证这一假设，我们使用光遗传学方法在下丘脑中激活 YR 神经元，同时记录对侧下丘脑中的其他神经元。我们发现，近 80%的谷氨酸能下丘神经元表达 Y 受体，为 NPY 信号调节局部回路提供了广泛的机会。此外，YR 神经元突触表现出适度的短期突触可塑性，这表明局部兴奋性回路在持续刺激期间保持对计算的影响。我们进一步发现，应用 LP-NPY 降低了下丘脑中的回返兴奋，表明 NPY 信号强烈调节听觉中脑中的局部回路功能。我们的研究结果表明，YR 兴奋性神经元在下丘脑中形成相互连接的局部回路，其对局部回路的影响受 NPY 信号调节。局部网络在下丘脑中的神经元计算中起着至关重要的作用。位于听觉中脑的下丘，在声音处理中起着重要作用，但下丘脑中的局部回路的组织仍知之甚少。在这里，我们表明表达神经肽 Y 受体 (YR 神经元) 的下丘神经元构成了下丘脑中的大部分兴奋性神经元，并形成相互连接的局部回路。此外，我们发现，NPY 是一种强大的神经调质，已知它可以调节其他脑区的神经元活动，它降低了 YR 神经元在下丘脑中局部回路中介导的广泛回返兴奋。因此，我们的研究结果表明，局部 NPY 信号是下丘脑中听觉计算的关键调节因子。
