Intrinsic physiology of inhibitory neurons changes over auditory development

Intrinsic physiology of inhibitory neurons changes over auditory development
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DOI:
10.1152/jn.00447.2017
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发表时间:
2018-01-01
影响因子:
2.5
通讯作者:
Hyson, Richard L.
Hyson, Richard L.
中科院分区:
医学3区
文献类型:
--
作者:
Carroll, Briana J.;Bertram, Richard;Hyson, Richard L.

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在听觉发育过程中,膜特性的变化促进了脑干兴奋性神经元编码声音方面的能力,包括刺激的水平和时间。其中一些变化与听力的开始相吻合,这表明声音驱动的神经活动产生了离子通道表达的发育可塑性。虽然已知兴奋性神经元的编码特性在成熟系统中受到抑制的调节,但尚不清楚脑干抑制神经元的膜特性是否也存在发育性变化。我们研究了鸟类听觉脑干,上橄榄核(SON)的主要抑制来源。目前的研究验证了这一假设,即与兴奋性神经元一样,这些抑制性神经元的膜特性在听力开始后发生变化。我们研究了听觉发育的不同阶段的SON神经元:胚胎14-16天(E14-E16),耳蜗神经节神经元刚刚开始对声音做出反应的时间;胚胎后期(E18-E19);以及孵化后(P0-P2)。我们采用体外全细胞膜片电生理学的方法来探讨SON的生理变化。在单穗水平和多穗行为水平上观察到了与年龄相关的变化。特别是,紧张性行为,即神经元在一系列当前步骤中维持紧张性放电的能力,在发育后期变得更加常见。电压钳记录和生物物理模型被用来研究与年龄相关的离子电流增加如何增强SON的兴奋性。我们的发现表明,钠和钾电流的同时增加是紧张性行为出现的基础。新&值得注意的是,本文首次研究了鸟类听觉系统抑制核中神经元生理学的异质性,并证明了这里出现的紧张性放电超过了发育。通过将计算机模拟与生理数据配对,我们表明在发育过程中钠通道和钾通道的增加对于紧张性放电的出现是必要的。
During auditory development, changes in membrane properties promote the ability of excitatory neurons in the brain stem to code aspects of sound, including the level and timing of a stimulus. Some of these changes coincide with hearing onset, suggesting that sound-driven neural activity produces developmental plasticity of ion channel expression. While it is known that the coding properties of excitatory neurons are modulated by inhibition in the mature system, it is unknown whether there are also developmental changes in the membrane properties of brain stem inhibitory neurons. We investigated the primary source of inhibition in the avian auditory brain stem, the superior olivary nucleus (SON). The present studies test the hypothesis that, as in excitatory neurons, the membrane properties of these inhibitory neurons change after hearing onset. We examined SON neurons at different stages of auditory development: embryonic days 14-16 (E14-E16), a time at which cochlear ganglion neurons are just beginning to respond to sound; later embryonic stages (E18-E19); and after hatching (P0 -P2). We used in vitro whole cell patch electrophysiology to explore physiological changes in SON. Age-related changes were observed at the level of a single spike and in multispiking behavior. In particular, tonic behavior, measured as a neuron's ability to sustain tonic firing over a range of current steps, became more common later in development. Voltage-clamp recordings and biophysical models were employed to examine how age-related increases in ion currents enhance excitability in SON. Our findings suggest that concurrent increases in sodium and potassium currents underlie the emergence of tonic behavior.NEW & NOTEWORTHY This article is the first to examine heterogeneity of neuronal physiology in the inhibitory nucleus of the avian auditory system and demonstrate that tonic firing here emerges over development. By pairing computer simulations with physiological data, we show that increases in both sodium and potassium channels over development are necessary for the emergence of tonic firing.