Bou-Flores C, Berger A J
Department of Physiology and Biophysics, School of Medicine, University of Washington, Seattle, Washington 98195-7290, USA.
J Neurophysiol. 2001 Apr;85(4):1543-51. doi: 10.1152/jn.2001.85.4.1543.
Interneuronal electrical coupling via gap junctions and chemical synaptic inhibitory transmission are known to have roles in the generation and synchronization of activity in neuronal networks. Uncertainty exists regarding the roles of these two modes of interneuronal communication in the central respiratory rhythm-generating system. To assess their roles, we performed studies on both the neonatal mouse medullary slice and en bloc brain stem-spinal cord preparations where rhythmic inspiratory motor activity can readily be recorded from both hypoglossal and phrenic nerve roots. The rhythmic inspiratory activity observed had two temporal characteristics: the basic respiratory frequency occurring on a long time scale and the synchronous neuronal discharge within the inspiratory burst occurring on a short time scale. In both preparations, we observed that bath application of gap-junction blockers, including 18 alpha-glycyrrhetinic acid, 18 beta-glycyrrhetinic acid, and carbenoxolone, all caused a reduction in respiratory frequency. In contrast, peak integrated phrenic and hypoglossal inspiratory activity was not significantly changed by gap-junction blockade. On a short-time-scale, gap-junction blockade increased the degree of synchronization within an inspiratory burst observed in both nerves. In contrast, opposite results were observed with blockade of GABA(A) and glycine receptors. We found that respiratory frequency increased with receptor blockade, and simultaneous blockade of both receptors consistently resulted in a reduction in short-time-scale synchronized activity observed in phrenic and hypoglossal inspiratory bursts. These results support the concept that the central respiratory system has two components: a rhythm generator responsible for the production of respiratory cycle timing and an inspiratory pattern generator that is involved in short-time-scale synchronization. In the neonatal rodent, properties of both components can be regulated by interneuronal communication via gap junctions and inhibitory synaptic transmission.
已知通过缝隙连接的神经元间电耦合和化学性突触抑制性传递在神经网络活动的产生和同步中发挥作用。关于这两种神经元间通讯模式在中枢呼吸节律产生系统中的作用尚不确定。为了评估它们的作用，我们对新生小鼠延髓切片和整体脑干 - 脊髓标本进行了研究，在这些标本中，可以很容易地从舌下神经根和膈神经根记录到节律性吸气运动活动。观察到的节律性吸气活动有两个时间特征：在长时间尺度上出现的基本呼吸频率，以及在短时间尺度上吸气爆发内的同步神经元放电。在这两种标本中，我们观察到，浴用缝隙连接阻滞剂，包括18α - 甘草次酸、18β - 甘草次酸和生胃酮，均导致呼吸频率降低。相比之下，缝隙连接阻断对膈神经和舌下神经吸气活动的峰值积分没有显著影响。在短时间尺度上，缝隙连接阻断增加了在两条神经中观察到的吸气爆发内的同步程度。相比之下，GABA(A)和甘氨酸受体阻断则产生了相反的结果。我们发现，受体阻断会使呼吸频率增加，同时阻断这两种受体始终会导致在膈神经和舌下神经吸气爆发中观察到的短时间尺度同步活动减少。这些结果支持这样一种概念，即中枢呼吸系统有两个组成部分：一个负责产生呼吸周期定时的节律发生器，以及一个参与短时间尺度同步的吸气模式发生器。在新生啮齿动物中，这两个组成部分的特性均可通过缝隙连接介导的神经元间通讯和抑制性突触传递来调节。
