Department of Anatomy and Neuroscience, University of Melbourne, VIC 3010, Australia.
Central Cardiovascular Regulation division, Department of Physiology, University of Melbourne, VIC 3010, Australia.
Neuroscience. 2018 Aug 1;384:1-13. doi: 10.1016/j.neuroscience.2018.05.009. Epub 2018 May 18.
The inhibitory peptide galanin is expressed within the retrotrapezoidal nucleus (RTN) - a key central chemoreceptor site that also contains the active expiratory oscillator. It was previously reported that microinjection of galanin into pre-Bötzinger complex - containing the inspiratory oscillator - exerts inhibitory effects on inspiratory motor output and respiratory rhythm. In neonatal rats, the present study aimed to investigate: (1) expression of galanin within the parafacial respiratory group (pFRG), which overlaps anatomically and functionally with the adult RTN, and; (2) effects of galanin on respiratory rhythm using the in vitro brainstem-spinal cord preparation. We showed that 14 ± 2% of Phox2b-immunoreactive (ir) neurons in the parafacial region were also galanin-ir. Galanin peptide expression was confirmed within 3/9 CO-sensitive, Phox2b-ir Pre-Inspiratory neurons (Pre-I) recorded in parafacial region. Bath application of galanin (0.1-0.2 µM): (1) decreased the duration of membrane depolarization in both Pre-I and inspiratory pFRG neurons, and; (2) decreased the number of C4 bursts that were associated with each burst in Pre-I neurons within the pFRG. In preparations showing episodic breathing at baseline, the respiratory patterning reverted to the 'normal' pattern of single, uniformly rhythmic C4 bursts (n = 10). In preparations with normal respiratory patterning at baseline, slowing of C4 rhythm (n = 7) resulted although rhythmic bursting in recorded Pre-I neurons remained unperturbed (n = 6). This study therefore demonstrates that galanin is expressed within the pFRG of neonatal rats, including neurons that are intrinsically chemosensitive. Overall the peptide has an inhibitory effect on inspiratory motor output, as previously shown in adults.
抑制肽甘丙肽在延髓背外侧核 (RTN) 中表达 - 这是一个关键的中枢化学感受器位点,其中还包含活跃的呼气振荡器。先前的研究表明,将甘丙肽微注射到包含吸气振荡器的 Pre-Bötzinger 复合体中,会对吸气运动输出和呼吸节律产生抑制作用。在新生大鼠中,本研究旨在调查:(1) 在副基底部呼吸组 (pFRG) 中甘丙肽的表达,该组在解剖学和功能上与成人 RTN 重叠;(2) 使用体外脑干-脊髓标本研究甘丙肽对呼吸节律的影响。我们发现,副基底部的 14±2%的 Phox2b 免疫反应性 (ir) 神经元也为甘丙肽-ir。在副基底部记录到的 3/9 对 CO 敏感的 Phox2b-ir 前吸气神经元 (Pre-I) 中,证实了甘丙肽肽的表达。甘丙肽 (0.1-0.2µM) 的浴液应用:(1) 降低了 Pre-I 和吸气 pFRG 神经元膜去极化的持续时间;(2) 降低了与 pFRG 中 Pre-I 神经元每个爆发相关的 C4 爆发的数量。在基线时有阵发性呼吸的标本中,呼吸模式恢复为“正常”的单个、均匀节律性 C4 爆发模式 (n=10)。在基线呼吸模式正常的标本中,尽管记录的 Pre-I 神经元中的节律性爆发仍未受到干扰 (n=6),但 C4 节律会减慢 (n=7)。因此,本研究表明甘丙肽在新生大鼠的 pFRG 中表达,包括内在化学敏感性的神经元。总的来说,该肽对吸气运动输出具有抑制作用,如以前在成人中观察到的那样。