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钠泄漏通道 NALCN 控制听觉神经元的自发性活动，并通过 α2-肾上腺素能受体介导突触调制。

The Na leak channel NALCN controls spontaneous activity and mediates synaptic modulation by α2-adrenergic receptors in auditory neurons.

机构信息

Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, Portland, United States.

Department of Physiology, Kitasato University School of Medicine, Sagamihara, Japan.

出版信息

Elife. 2024 Jan 10;12:RP89520. doi: 10.7554/eLife.89520.

DOI:10.7554/eLife.89520
PMID:38197879
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10945507/
Abstract

Cartwheel interneurons of the dorsal cochlear nucleus (DCN) potently suppress multisensory signals that converge with primary auditory afferent input, and thus regulate auditory processing. Noradrenergic fibers from locus coeruleus project to the DCN, and α2-adrenergic receptors inhibit spontaneous spike activity but simultaneously enhance synaptic strength in cartwheel cells, a dual effect leading to enhanced signal-to-noise for inhibition. However, the ionic mechanism of this striking modulation is unknown. We generated a glycinergic neuron-specific knockout of the Na leak channel NALCN in mice and found that its presence was required for spontaneous firing in cartwheel cells. Activation of α2-adrenergic receptors inhibited both NALCN and spike generation, and this modulation was absent in the NALCN knockout. Moreover, α2-dependent enhancement of synaptic strength was also absent in the knockout. GABA receptors mediated inhibition through NALCN as well, acting on the same population of channels as α2 receptors, suggesting close apposition of both receptor subtypes with NALCN. Thus, multiple neuromodulatory systems determine the impact of synaptic inhibition by suppressing the excitatory leak channel, NALCN.

摘要

耳蜗背核（DCN）中的车轮神经元强烈抑制与初级听觉传入输入会聚的多感觉信号，从而调节听觉处理。来自蓝斑的去甲肾上腺素能纤维投射到 DCN，α2-肾上腺素能受体抑制自发尖峰活动，但同时增强车轮细胞中的突触强度，这种双重作用导致抑制的信噪比增强。然而，这种显著调节的离子机制尚不清楚。我们在小鼠中生成了甘氨酸能神经元特异性 NALCN 钠泄漏通道敲除，并发现其存在是车轮细胞自发放电所必需的。α2-肾上腺素能受体的激活抑制了 NALCN 和尖峰产生，而在 NALCN 敲除中不存在这种调制。此外，在敲除体中也不存在 α2 依赖性的突触强度增强。GABA 受体也通过 NALCN 介导抑制，作用于与 α2 受体相同的通道群体，表明两种受体亚型与 NALCN 紧密接近。因此，通过抑制兴奋性泄漏通道 NALCN，多种神经调制系统决定了突触抑制的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e23/10945507/68e45623a7e8/elife-89520-fig8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e23/10945507/68e45623a7e8/elife-89520-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e23/10945507/271b29f23340/elife-89520-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e23/10945507/79a562e246e8/elife-89520-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e23/10945507/3ec6bfad9565/elife-89520-fig1-figsupp2.jpg
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