The vestibulo- and preposito-cerebellar cholinergic neurons of a ChAT-tdTomato transgenic rat exhibit heterogeneous firing properties and the expression of various neurotransmitter receptors.
The vestibulo- and preposito-cerebellar cholinergic neurons of a ChAT-tdTomato transgenic rat exhibit heterogeneous firing properties and the expression of various neurotransmitter receptors.
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ChAT-tdTomato 转基因大鼠的前庭和前小脑胆碱能神经元表现出异质放电特性和各种神经递质受体的表达。
DOI：
10.1111/ejn.12509
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Saito Y.
中科院分区：
文献类型：
--
作者：
Zhang Y;Kaneko R;Yanagawa Y;Saito Y.
小脑的功能是由胆碱能苔藓纤维的输入，主要来自前庭内侧核（MVN）和前置舌下核（PHN）的调节。与越来越多的证据表明胆碱能传递及其在小脑中的功能意义相反，胆碱能投射神经元（ChPN）的内在和突触特性尚未得到澄清。在这项研究中，我们产生了胆碱乙酰转移酶（ChAT）-tdTomato转基因大鼠，它在胆碱能神经元中特异性表达荧光蛋白tdTomato，并使用它们来研究通过脑干切片中的全细胞记录逆行标记鉴定的ChPN的反应特性。在响应电流脉冲，ChPN表现出两个afterhyperpolarisation（AHP）的配置文件和三个射击模式，主要的AHP和射击性能之间的MVN和PHN不同。形态学上，ChPN根据其索马大小和树突延伸分为两种类型。对时变正弦电流刺激的放电响应的分析表明，ChPN根据输入频率表现出不同的放电模式。观察到每个放电模式的最大频率在表现出不同放电模式的神经元之间是不同的。对应用神经递质受体激动剂的电流反应分析显示，ChPN表达（i）AMPA和NMDA型谷氨酸受体，（ii）GABA和甘氨酸受体，以及（iii）毒蕈碱和烟碱乙酰胆碱受体。MVN ChPN的这些受体介导的电流反应与PHN ChPN的这些受体介导的电流反应没有差异。这些发现表明，ChPN接收各种突触输入，并在不同频率下对这些输入进行适当编码。
Cerebellar function is regulated by cholinergic mossy fiber inputs that are primarily derived from the medial vestibular nucleus (MVN) and prepositus hypoglossi nucleus (PHN). In contrast to the growing evidence surrounding cholinergic transmission and its functional significance in the cerebellum, the intrinsic and synaptic properties of cholinergic projection neurons (ChPNs) have not been clarified. In this study, we generated choline acetyltransferase (ChAT)‐tdTomato transgenic rats, which specifically express the fluorescent protein tdTomato in cholinergic neurons, and used them to investigate the response properties of ChPNs identified via retrograde labeling using whole‐cell recordings in brainstem slices. In response to current pulses, ChPNs exhibited two afterhyperpolarisation (AHP) profiles and three firing patterns; the predominant AHP and firing properties differed between the MVN and PHN. Morphologically, the ChPNs were separated into two types based on their soma size and dendritic extensions. Analyses of the firing responses to time‐varying sinusoidal current stimuli revealed that ChPNs exhibited different firing modes depending on the input frequencies. The maximum frequencies in which each firing mode was observed were different between the neurons that exhibited distinct firing patterns. Analyses of the current responses to the application of neurotransmitter receptor agonists revealed that the ChPNs expressed (i) AMPA‐ and NMDA‐type glutamate receptors, (ii) GABAAand glycine receptors, and (iii) muscarinic and nicotinic acetylcholine receptors. The current responses mediated by these receptors of MVN ChPNs were not different from those of PHN ChPNs. These findings suggest that ChPNs receive various synaptic inputs and encode those inputs appropriately across different frequencies.