Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons.
Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons.
复制标题
发育期尼古丁暴露对节律性活跃舌下运动神经元谷氨酸能神经传递的影响。
DOI：
10.1016/j.expneurol.2016.07.023
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发表时间：
2017
影响因子：
5.3
通讯作者：
Fregosi,RalphF
中科院分区：
文献类型：
--
作者：
Cholanian,Marina;Powell,GregoryL;Levine,RichardB;Fregosi,RalphF
发育性尼古丁暴露（DNE）与新生儿心肺、智力和行为异常的风险增加有关，是早产呼吸暂停、觉醒反应改变和婴儿猝死综合征的危险因素。DNE后尼古丁乙酰胆碱受体信号（nAChRs）的改变导致控制呼吸的神经网络中的兴奋性神经传递的改变，包括对舌下运动核注射AMPA的兴奋性反应增强。在这里，我们报告了旨在探索可能的突触后和突触前机制的实验，这些机制可能是这种可塑性的基础。在妊娠第5天，通过微型渗透泵将怀孕母鼠暴露于尼古丁或生理盐水中。我们使用全细胞膜片钳电生理技术记录了新生大鼠幼崽（对照组26个，DNE细胞24个）厚髓片舌下运动神经元（XIIMNs）。为了将我们的研究结果转化为DNE的呼吸相关后果，我们只研究了接受呼吸中枢模式发生器节律性兴奋驱动的xiimn。利用河蟹毒素从突触前输入中分离XIIMNs，并在电压箝位下研究其对谷氨酸（glutamate）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）的突触后反应。DNE对谷氨酸和AMPA诱发的内向电流无影响。然而，在DNE动物的细胞中，AMPA溶液应用与振幅分布右移相关（P= 0.0004），但没有改变微型兴奋性突触后电流（mEPSCs）的事件间间隔分布。DNE对谷氨酸应用或（非刺激）基线条件下诱发的mEPSC振幅或频率没有影响。因此，在AMPA存在的情况下，DNE与量子大小的微小但显著的增加有关，但谷氨酸释放的概率没有变化。
Developmental nicotine exposure (DNE) is associated with increased risk of cardiorespiratory, intellectual, and behavioral abnormalities in neonates, and is a risk factor for apnea of prematurity, altered arousal responses and Sudden Infant Death Syndrome. Alterations in nicotinic acetylcholine receptor signaling (nAChRs) after DNE lead to changes in excitatory neurotransmission in neural networks that control breathing, including a heightened excitatory response to AMPA microinjection into the hypoglossal motor nucleus. Here, we report on experiments designed to probe possible postsynaptic and presynaptic mechanisms that may underlie this plasticity. Pregnant dams were exposed to nicotine or saline via an osmotic mini-pump implanted on the 5th day of gestation. We used whole-cell patch clamp electrophysiology to record from hypoglossal motoneurons (XIIMNs) in thick medullary slices from neonatal rat pups (N= 26 control and 24 DNE cells). To enable the translation of our findings to breathing-related consequences of DNE, we only studied XIIMNs that were receiving rhythmic excitatory drive from the respiratory central pattern generator. Tetrodotoxin was used to isolate XIIMNs from presynaptic input, and their postsynaptic responses to bath application ofl-glutamic acid (glutamate) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were studied under voltage clamp. DNE had no influence on inward current magnitude evoked by either glutamate or AMPA. However, in cells from DNE animals, bath application of AMPA was associated with a right shift in the amplitude distribution (P= 0.0004), but no change in the inter-event interval distribution of miniature excitatory postsynaptic currents (mEPSCs). DNE had no influence on mEPSC amplitude or frequency evoked by glutamate application, or under (unstimulated) baseline conditions. Thus, in the presence of AMPA, DNE is associated with a small but significant increase in quantal size, but no change in the probability of glutamate release.