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小鼠外侧上橄榄核抑制性和兴奋性主神经元的突触驱动

Synaptic Drive onto Inhibitory and Excitatory Principal Neurons of the Mouse Lateral Superior Olive.

作者信息

Haragopal Hariprakash, Voytek Mara J, Winters Bradley D

机构信息

Department of Biological Sciences and University Hospitals - NEOMED Hearing Research Center, Northeast Ohio Medical University, Rootstown, Ohio, 44272.

Department of Biological Sciences and University Hospitals - NEOMED Hearing Research Center, Northeast Ohio Medical University, Rootstown, Ohio, 44272

出版信息

eNeuro. 2025 May 8;12(5). doi: 10.1523/ENEURO.0106-25.2025. Print 2025 May.

Abstract

Principal neurons (PNs) of the lateral superior olive (LSO) are a critical component of brain circuits that compare information between the two ears to extract sound source-location-related cues. LSO PNs are not a homogenous group but differ in their transmitter type, intrinsic membrane properties, and projection pattern to higher processing centers in the inferior colliculus. Glycinergic inhibitory LSO PNs have higher input resistance than glutamatergic excitatory LSO PNs (∼double). This suggests that the inhibitory cell type has a lower minimum input or signal intensity required to produce an output (activation threshold) which may impact how they integrate binaural inputs. However, cell-type-specific differences in the strength of synaptic drive could offset or accentuate such differences in intrinsic excitability and have not been assessed. To evaluate this possibility, we used a knock-in mouse model to examine spontaneous and electrically stimulated (evoked) synaptic events in LSO PN types using voltage-clamp technique. Both excitatory and inhibitory spontaneous postsynaptic currents were larger in inhibitory LSO PNs, but evoked events were not. Additionally, we found that LSO PN types had inputs with similar short-term plasticity and number of independent fibers. An important contrast was that inhibitory LSO PNs received inhibitory inputs with slower decay kinetics which could impact integrative functions. These data suggest that synaptic inputs onto LSO PNs are unlikely to offset excitability differences. Differences in activation threshold along with transmitter type and projection laterality may allow for distinct roles for LSO PN types in inferior colliculus information processing.

摘要

外侧上橄榄核(LSO)的主神经元(PNs)是脑回路的关键组成部分,该脑回路比较两耳之间的信息以提取与声源位置相关的线索。LSO主神经元不是一个同质群体,而是在其递质类型、内在膜特性以及向下丘更高处理中心的投射模式方面存在差异。甘氨酸能抑制性LSO主神经元的输入电阻高于谷氨酸能兴奋性LSO主神经元(约为两倍)。这表明抑制性细胞类型产生输出所需的最小输入或信号强度较低(激活阈值),这可能会影响它们整合双耳输入的方式。然而,突触驱动强度的细胞类型特异性差异可能会抵消或加剧内在兴奋性的这种差异,而这一点尚未得到评估。为了评估这种可能性,我们使用了一种敲入小鼠模型,采用电压钳技术来检查LSO主神经元类型中的自发和电刺激(诱发)突触事件。抑制性LSO主神经元中的兴奋性和抑制性自发突触后电流均较大,但诱发事件并非如此。此外,我们发现LSO主神经元类型具有具有相似短期可塑性和独立纤维数量的输入。一个重要的对比是,抑制性LSO主神经元接收具有较慢衰减动力学的抑制性输入,这可能会影响整合功能。这些数据表明,作用于LSO主神经元的突触输入不太可能抵消兴奋性差异。激活阈值的差异以及递质类型和投射侧性的差异可能使LSO主神经元类型在下丘信息处理中发挥不同的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cb1/12061355/f8dea3d23607/eneuro-12-ENEURO.0106-25.2025-g001.jpg

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