Developmental nicotine exposure alters AMPA neurotransmission in the hypoglossal motor nucleus and pre-Botzinger complex of neonatal rats.
Developmental nicotine exposure alters AMPA neurotransmission in the hypoglossal motor nucleus and pre-Botzinger complex of neonatal rats.
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DOI：
10.1523/jneurosci.3711-12.2013
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发表时间：
2013-02-06
期刊：
影响因子：
--
通讯作者：
Fregosi RF
中科院分区：
文献类型：
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作者：
Jaiswal SJ;Pilarski JQ;Harrison CM;Fregosi RF
发育性尼古丁暴露（DNE）会影响吸烟母亲所生新生儿的中枢呼吸控制。我们之前表明，DNE 增强了脑干对 AMPA 浴应用的呼吸运动反应，尽管尚不清楚哪些脑干呼吸神经元介导了这些作用。在这里，我们研究了 DNE 如何影响前 Bötzinger 复合体 (pre-BötC) 和舌下运动核 (XIIMN) 中的 AMPA 型谷氨酸神经传递，这些神经元群位于延髓中，是正常呼吸所必需的。使用新生大鼠的节律性脑干切片，我们将 AMPA 显微注射到前 BötC 或 XIIMN 中，同时记录 XII 神经根 (XIIn) 作为呼吸运动输出的指数。 AMPA 显微注射到 XIIMN 后，DNE 增加了强直活动的持续时间并降低了节律爆发幅度。此外，在将 AMPA 注射到预 BötC 中后，DNE 导致呼吸爆发频率增加。 XII 运动神经元的全细胞膜片钳记录表明，DNE 增加了运动神经元的兴奋性，但没有改变内向电流。免疫组织化学研究表明，DNE 降低了 XIIMN 和 pre-BötC 中谷氨酸受体亚基 2 和 3 (GluR2/3) 的表达。我们的数据表明，DNE 改变 XIIMN 和前 BötC 中的 AMPAergic 突触传递，尽管发生这种情况的机制尚不清楚。我们认为 DNE 诱导的 GluR2/3 减少可能代表了补偿细胞兴奋性增加的尝试，这与稳态可塑性的机制一致。
Developmental nicotine exposure (DNE) impacts central respiratory control in neonates born to smoking mothers. We previously showed that DNE enhances the respiratory motor response to bath application of AMPA to the brainstem, although it was unclear which brainstem respiratory neurons mediated these effects. Here we examine how DNE influences AMPA-type glutamatergic neurotransmission in the pre-Bötzinger complex (pre-BötC) and the hypoglossal motor nucleus (XIIMN), which are neuronal populations located in the medulla that are necessary for normal breathing. Using rhythmic brainstem slices from neonatal rats, we microinjected AMPA into the pre-BötC or the XIIMN while recording from XII nerve rootlets (XIIn) as an index of respiratory motor output. DNE increased the duration of tonic activity and reduced rhythmic burst amplitude after AMPA microinjection into the XIIMN. Also, DNE led to an increase in respiratory burst frequency after AMPA injection into the pre-BötC. Whole-cell patch-clamp recordings of XII motoneurons showed that DNE increased motoneuron excitability but did not change inward currents. Immunohistochemical studies indicate that DNE reduced the expression of glutamate receptor subunits 2 and 3 (GluR2/3) in the XIIMN and the pre-BötC. Our data show that DNE alters AMPAergic synaptic transmission in both the XIIMN and pre-BötC, although the mechanism by which this occurs is unclear. We suggest that the DNE-induced reduction in GluR2/3 may represent an attempt to compensate for increased cell excitability, consistent with mechanisms underlying homeostatic plasticity.