Kang Jun-Jun, Liang Wei-Hua, Lam Chun-Sing, Huang Xiao-Feng, Yang Shou-Jing, Wong-Riley Margaret T T, Fung Man-Lung, Liu Ying-Ying
Institute of Neurosciences, The Fourth Military Medical University, Xi'an 710032, PR China.
Department of Pathology and Pathophysiology, The Fourth Military Medical University, Xi'an 710032, PR China.
Exp Neurol. 2017 Jan;287(Pt 2):165-175. doi: 10.1016/j.expneurol.2016.05.035. Epub 2016 May 27.
The rostral ventrolateral medulla (RVLM) contains cardiovascular-related catecholaminergic neurons and respiratory-related pre-Bötzinger complex (pre-BötC) neurons, which are intermingled and functionally connected for coordinating cardiorespiratory activities. Daily acute intermittent hypoxia (dAIH) is known to elicit respiratory plasticity. However, it is unclear if the catecholaminergic neurons directly synapse onto pre-BötC neurons, and if the local circuitry exhibits plasticity when exposed to dAIH. The present study was aimed to determine the synaptic phenotypes between dopamine-β-hydroxylase (DβH)-immunoreactive (ir) catecholaminergic neurons and neurokinin 1 receptor (NK1R)-ir pre-BötC neurons, and the effect of dAIH on the neuronal network. Immunofluorescence histochemistry was used to reveal immunoreactivities of DβH and NK1R in the RVLM of normoxic and dAIH rats. Synaptic phenotypes were examined with double-labeling immunoelectron microscopy. We found that DβH immunoreactivity was expressed in somata and processes, some of which were in close apposition to NK1R-ir pre-BötC neurons. DβH-ir gold particles were localized to somata, dendrites, and axonal terminals. DβH-ir terminals formed asymmetric synapses, and occasionally, symmetric synapses in the pre-BötC, featuring the local circuitry. Of the synapses, 28% in normoxic and 29.6% in dAIH groups were apposed to NK1R-ir dendrites. Significant increases in DβH expression and NK1R-ir processes were found in the dAIH group. Moreover, the area and number of processes in close appositions were significantly elevated, strongly suggesting that dAIH induced plasticity with increased connections and interactions between the cardiovascular- and respiratory-related neurons in the local circuitry. In conclusion, asymmetric synapses are predominant in the crosstalk between catecholaminergic and pre-BötC neurons in the RVLM, elaborating excitatory transmission driving the coupling of cardiorespiratory activities. The neural network manifests plasticity in response to dAIH challenge.
延髓头端腹外侧区（RVLM）包含与心血管相关的儿茶酚胺能神经元和与呼吸相关的前包钦格复合体（pre-BötC）神经元，它们相互交织并在功能上相连，以协调心肺活动。已知每日急性间歇性缺氧（dAIH）会引发呼吸可塑性。然而，尚不清楚儿茶酚胺能神经元是否直接与pre-BötC神经元形成突触，以及当暴露于dAIH时局部神经回路是否表现出可塑性。本研究旨在确定多巴胺-β-羟化酶（DβH）免疫反应性（ir）儿茶酚胺能神经元与神经激肽1受体（NK1R）-ir pre-BötC神经元之间的突触表型，以及dAIH对神经网络的影响。免疫荧光组织化学用于揭示常氧和dAIH大鼠RVLM中DβH和NK1R的免疫反应性。用双标记免疫电子显微镜检查突触表型。我们发现DβH免疫反应性在胞体和突起中表达，其中一些与NK1R-ir pre-BötC神经元紧密相邻。DβH-ir金颗粒定位于胞体、树突和轴突终末。DβH-ir终末在pre-BötC中形成不对称突触，偶尔也形成对称突触，具有局部神经回路的特征。在这些突触中，常氧组有28%、dAIH组有29.6%与NK1R-ir树突相邻。在dAIH组中发现DβH表达和NK1R-ir突起显著增加。此外，紧密相邻的突起的面积和数量显著增加，强烈表明dAIH诱导了可塑性，增加了局部神经回路中与心血管和呼吸相关神经元之间的连接和相互作用。总之，不对称突触在RVLM中儿茶酚胺能神经元和pre-BötC神经元之间的相互作用中占主导地位，阐述了驱动心肺活动耦合的兴奋性传递。神经网络在应对dAIH挑战时表现出可塑性。
