Takakura Ana C, Moreira Thiago S, West Gavin H, Gwilt Justin M, Colombari Eduardo, Stornetta Ruth L, Guyenet Patrice G
Department of Pharmacology, University of Virginia Health System, Charlottesville, VA 22908-0735, USA.
J Neurophysiol. 2007 Jul;98(1):374-81. doi: 10.1152/jn.00322.2007. Epub 2007 Apr 25.
The retrotrapezoid nucleus (RTN) contains central respiratory chemoreceptors that are inhibited by activation of slowly adapting pulmonary stretch receptors (SARs). Here we examine whether RTN inhibition by lung inflation could be mediated by a direct projection from SAR second-order neurons (pump cells). Pump cells (n = 56 neurons, 13 rats) were recorded in the nucleus of solitary tract (NTS) of halothane-anesthetized rats with intact vagus nerves. Pump cells had discharges that coincided with lung inflation as monitored by the tracheal pressure. Their activity increased when end-expiratory pressure was raised and stopped instantly when ventilation was interrupted in expiration. Many pump cells could be antidromically activated from RTN (12/36). Nine of those were labeled with biotinamide. Of these nine cells, eight contained glutamic acid decarboxylase 67 (GAD67) mRNA and seven were found to reside in the lower half of the interstitial subnucleus of NTS (iNTS). Using the retrograde tracer cholera toxin-B, we confirmed that neurons located in or close to iNTS innervate RTN (two rats). Many such neurons contained GAD67 mRNA and a few contained glycine transporter2 (GLYT2) mRNA. Anterograde tract tracing with biotinylated dextranamide (four rats) applied to iNTS also confirmed that this region innervates RTN by a predominantly GABAergic projection. This work confirms that many rat NTS pump cells are located in and around the interstitial subnucleus at area postrema level. We demonstrate that a GABAergic subset of these pump cells innervates the RTN region. We conclude that these inhibitory neurons probably contact RTN chemoreceptors and mediate their inhibition by lung inflation.
延髓后梯形核（RTN）包含中枢呼吸化学感受器，这些感受器会被慢适应性肺牵张感受器（SARs）的激活所抑制。在此，我们研究肺部充气对RTN的抑制作用是否可由SAR二级神经元（泵细胞）的直接投射介导。在迷走神经完整的氟烷麻醉大鼠的孤束核（NTS）中记录泵细胞（n = 56个神经元，13只大鼠）。泵细胞的放电与通过气管压力监测的肺部充气同步。当呼气末压力升高时其活动增加，而在呼气过程中通气中断时立即停止。许多泵细胞可被来自RTN的逆向激活（12/36）。其中9个用生物素酰胺标记。在这9个细胞中，8个含有谷氨酸脱羧酶67（GAD67）mRNA，7个位于NTS间质亚核（iNTS）的下半部分。使用逆行示踪剂霍乱毒素-B，我们证实位于iNTS内或附近的神经元支配RTN（2只大鼠）。许多这样的神经元含有GAD67 mRNA，少数含有甘氨酸转运体2（GLYT2）mRNA。将生物素化葡聚糖胺应用于iNTS进行顺行束路追踪（4只大鼠）也证实该区域通过主要为GABA能的投射支配RTN。这项工作证实许多大鼠NTS泵细胞位于最后区水平的间质亚核及其周围。我们证明这些泵细胞的一个GABA能亚群支配RTN区域。我们得出结论，这些抑制性神经元可能与RTN化学感受器接触，并介导肺部充气对它们的抑制作用。
