Lieske Steven P, Ramirez Jan-Marino
Committee on Neurobiology, The University of Chicago, 1027 E. 57th St., Chicago, IL 60637-1508, USA.
J Neurophysiol. 2006 Mar;95(3):1334-44. doi: 10.1152/jn.00506.2004.
The in vitro respiratory network contained in the transverse brain stem slice of mice simultaneously generates fast (approximately 15 min(-1)) and slow ( approximately 0.5 min(-1)) rhythmic activities corresponding to fictive eupnea ("normal" breathing) and fictive sighs. We show that these two activity patterns are differentially controlled through the modulatory actions of metabotropic glutamate receptors (mGluRs). Sighs were selectively inhibited by agonists of the group III mGluRs according to a pharmacological profile most consistent with activation of mGluR8. Sighs were also blocked by the supposedly inactive L-isomer of the widely used N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanoic acid (L-AP5, 5 microM), an effect that was abolished in the presence of group III mGluR antagonists. Excitatory postsynaptic potentials (EPSPs) were recorded in pre-Bötzinger Complex neurons after stimulation of the contralateral ventral respiratory group (VRG); evoked EPSP amplitude was variably reduced after bath application of the group III agonist L-serine-O-phosphate (L-SOP), with an average reduction of 15%. Therefore although group III mGluRs do play a role in regulating synapse strength, this seems to be only a minor factor in the regulation of synapses made by midline-crossing axons. Intrinsic modulation of the respiratory central pattern generator by mGluRs appears to be an essential component of the multifunctionality that characterizes this network.
小鼠横断脑干切片中包含的体外呼吸网络同时产生对应于虚构的平静呼吸（“正常”呼吸）和虚构叹息的快速（约15次/分钟）和缓慢（约0.5次/分钟）节律性活动。我们表明，这两种活动模式通过代谢型谷氨酸受体（mGluRs）的调节作用受到不同的控制。根据与mGluR8激活最一致的药理学特征，III组mGluRs的激动剂选择性地抑制叹息。广泛使用的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂2-氨基-5-磷酸戊酸（L-AP5，5 microM）的所谓无活性L-异构体也能阻断叹息，在存在III组mGluR拮抗剂的情况下这种作用被消除。在刺激对侧腹侧呼吸组（VRG）后，在前包钦格复合体神经元中记录到兴奋性突触后电位（EPSPs）；在浴用III组激动剂L-丝氨酸-O-磷酸（L-SOP）后，诱发的EPSP幅度有不同程度的降低，平均降低15%。因此，尽管III组mGluRs确实在调节突触强度中起作用，但这似乎只是调节中线交叉轴突形成的突触的一个次要因素。mGluRs对呼吸中枢模式发生器的内在调节似乎是该网络多功能性的一个重要组成部分。
