Department of Pharmacology and Physiology, The George Washington University, Washington, DC 20037, USA.
J Neurophysiol. 2013 Aug;110(3):672-9. doi: 10.1152/jn.01054.2012. Epub 2013 May 8.
Cardiovascular function is regulated by a dynamic balance composed of sympathetic and parasympathetic activity. Sympathoexcitatory presympathetic neurons (PSNs) in the rostral ventrolateral medulla project directly to cardiac and vasomotor sympathetic preganglionic neurons in the spinal cord. In proximity to the PSNs in the medulla, there are preganglionic cardiac vagal neurons (CVNs) within the nucleus ambiguus, which are critical for parasympathetic control of heart rate. Both CVNs and PSNs receive GABAergic synaptic inputs that change with challenges such as hypoxia and hypercapnia (H/H). Autonomic control of cardiovascular function undergoes significant changes during early postnatal development; however, little is known regarding postnatal maturation of GABAergic neurotransmission to these neurons. In this study, we compared changes in GABAergic inhibitory postsynaptic currents (IPSCs) in CVNs and PSNs under control conditions and during H/H in postnatal day 2-5 (P5), 16-20 (P20), and 27-30 (P30) rats using an in vitro brainstem slice preparation. There was a significant enhancement in GABAergic neurotransmission to both CVNs and PSNs at age P20 compared with P5 and P30, with a more pronounced increase in PSNs. H/H did not significantly alter this enhanced GABAergic neurotransmission to PSNs in P20 animals. However, the frequency of GABAergic IPSCs in PSNs was reduced by H/H in P5 and P30 animals. In CVNs, H/H elicited an inhibition of GABAergic neurotransmission in all ages studied, with the most pronounced inhibition occurring at P20. In conclusion, there are critical development periods at which significant rearrangement occurs in the central regulation of cardiovascular function.
心血管功能受交感和副交感活动组成的动态平衡调节。延髓头端腹外侧区的交感兴奋节前神经元（PSNs）直接投射到脊髓中的心脏和血管交感节前神经元。在延髓中的 PSNs 附近，有位于疑核内的节前心脏迷走神经元（CVNs），它们对于心率的副交感控制至关重要。CVNs 和 PSNs 都接收 GABA 能突触输入，这些输入会随着缺氧和高碳酸血症（H/H）等挑战而发生变化。心血管自主功能在出生后早期发育过程中会发生重大变化；然而，对于这些神经元的 GABA 能神经传递的出生后成熟过程，人们知之甚少。在这项研究中，我们使用体外脑干切片制备，比较了出生后第 2-5 天（P5）、第 16-20 天（P20）和第 27-30 天（P30）大鼠在对照条件下和 H/H 期间 CVNs 和 PSNs 中 GABA 能抑制性突触后电流（IPSCs）的变化。与 P5 和 P30 相比，P20 时 CVNs 和 PSNs 的 GABA 能神经传递明显增强，PSNs 的增强更为明显。H/H 并没有显著改变 P20 动物 PSNs 中这种增强的 GABA 能神经传递。然而，在 P5 和 P30 动物中，PSNs 中的 GABA 能 IPSC 频率在 H/H 时降低。在 CVNs 中，H/H 在所有研究的年龄中均引起 GABA 能神经传递的抑制，在 P20 时抑制最为明显。总之，在心血管功能的中枢调节中，存在着关键的发育时期，在此期间会发生重大的重新排列。
