Neuropeptide Y signaling regulates recurrent excitation in the auditory midbrain.
Neuropeptide Y signaling regulates recurrent excitation in the auditory midbrain.
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神经肽 Y 信号传导调节听觉中脑的反复兴奋。
DOI：
10.1101/2023.05.16.540954
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发表时间：
2023
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;Drotos,AudreyC;Pirrone,TrinityM;Versalle,TrevorS;Bock,Amanda;Roberts,MichaelT
神经肽在塑造神经元回路的组织和功能中发挥着关键作用。在位于听觉中脑的下丘 (IC) 中，神经肽 Y (NPY) 由一类投射到 IC 局部和外部的 GABA 能神经元表达。 IC 中的大多数神经元都有局部轴突侧支；然而，IC 中局部电路的组织和功能仍然未知。我们之前发现 IC 中的兴奋性神经元可以表达 NPY Y1 受体 (Y1R+)，并且应用 Y1R 激动剂 [Leu31, Pro34]-NPY (LP-NPY) 会降低 Y1R+ 神经元的兴奋性。由于 NPY 信号调节其他大脑区域的反复兴奋，我们假设 Y1R+ 神经元在 IC 中形成互连的局部回路，并且 NPY 降低了这些回路中反复兴奋的强度。为了检验这一假设，我们使用光遗传学激活两性小鼠的 Y1R+ 神经元，同时记录同侧 IC 中的其他神经元。我们发现近 80% 的谷氨酸能 IC 神经元表达 Y1 受体，为 NPY 信号传导调节局部回路提供了广泛的机会。此外，Y1R+神经元突触表现出适度的短期突触可塑性，表明局部兴奋性电路在持续刺激期间保持对计算的影响。我们进一步发现，LP-NPY 的应用减少了 IC 中的反复兴奋，表明 NPY 信号强烈调节听觉中脑的局部电路功能。我们的研究结果表明，Y1R+兴奋性神经元在 IC 中形成互连的局部回路，它们对局部回路的影响受到 NPY 信号传导的调节。意义陈述局部网络在塑造大脑中的神经元计算方面发挥着基础作用。 IC 位于听觉中脑，在声音处理中发挥着重要作用，但 IC 中局部电路的组织很大程度上未知。在这里，我们发现表达神经肽 Y1 受体（Y1R+神经元）的 IC 神经元构成了 IC 中的大部分兴奋性神经元，并形成互连的局部回路。此外，我们发现 NPY 是一种强大的神经调节剂，已知可塑造其他大脑区域的神经元活动，可减少局部 IC 电路中由 Y1R+ 神经元介导的广泛的反复兴奋。因此，我们的结果表明局部 NPY 信号是 IC 中听觉计算的关键调节器。
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 Y1receptor (Y1R+) and application of the Y1R agonist, [Leu31, Pro34]-NPY (LP-NPY), decreases the excitability of Y1R+neurons. As NPY signaling regulates recurrent excitation in other brain regions, we hypothesized that Y1R+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 Y1R+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 Y1receptor, providing extensive opportunities for NPY signaling to regulate local circuits. Additionally, Y1R+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 Y1R+excitatory neurons form interconnected local circuits in the IC, and their influence over local circuits is regulated by NPY signaling.SIGNIFICANCE STATEMENTLocal 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 Y1receptor (Y1R+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 Y1R+neurons in local IC circuits. Thus, our results suggest that local NPY signaling is a key regulator of auditory computations in the IC.