Perturbations of Respiratory Rhythm and Pattern by Disrupting Synaptic Inhibition within Pre-Botzinger and Botzinger Complexes
Perturbations of Respiratory Rhythm and Pattern by Disrupting Synaptic Inhibition within Pre-Botzinger and Botzinger Complexes
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DOI：
10.1523/eneuro.0011-16.2016
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发表时间：
2016-03-01
期刊：
影响因子：
3.4
通讯作者：
Smith, Jeffrey C.
中科院分区：
文献类型：
--
作者：
Marchenko, Vitaliy;Koizumi, Hidehiko;Smith, Jeffrey C.
前波青格（pre-Botzinger）和波青格（Botzinger）复合体是包含中间神经元的脑干隔室，被认为在哺乳动物的呼吸节律和运动模式的产生中起关键作用。目前的模型假设，节奏的产生和吸气-呼气模式的协调都涉及这些区域内部和之间的抑制性突触相互作用。这两个区域都含有甘氨酸能和gaba能神经元，这些区域的节律性活跃神经元接受适当协调的相抑制，这是正常三相呼吸模式产生所必需的。然而，最近的实验试图破坏成年大鼠btc前和btc突触后的甘氨酸能和gaba能抑制，这些实验质疑突触抑制在这些区域的关键作用，以及btc的重要性，这与之前的生理和药理学研究相矛盾。为了进一步评估突触抑制和BotC的作用，我们将GABA(A)受体拮抗剂加巴嗪和甘氨酸受体拮抗剂士的宁双侧微注射到麻醉成年大鼠的BotC前或BotC中，并将其灌注到幼年大鼠的原位脑干脊髓制剂中。微注射Muscimol以抑制BotC前或BotC的神经元活性。在这两种制剂中，破坏pre-BotC或BotC内的抑制会引起主要的位点特异性节律扰动，并破坏三相运动模式，在一些实验中终止节律性运动输出。抑制BotC的活动也会严重扰乱节律和运动模式。我们的结论是，抑制回路在前BotC和BotC内部和之间的相互作用对节律发生起着关键的调节作用，并且是正常呼吸运动模式产生所必需的。
The pre-Botzinger (pre-BotC) and Botzinger (BotC) complexes are the brainstem compartments containing interneurons considered to be critically involved in generating respiratory rhythm and motor pattern in mammals. Current models postulate that both generation of the rhythm and coordination of the inspiratory-expiratory pattern involve inhibitory synaptic interactions within and between these regions. Both regions contain glycinergic and GABAergic neurons, and rhythmically active neurons in these regions receive appropriately coordinated phasic inhibition necessary for generation of the normal three-phase respiratory pattern. However, recent experiments attempting to disrupt glycinergic and GABAergic postsynaptic inhibition in the pre-BotC and BotC in adult rats in vivo have questioned the critical role of synaptic inhibition in these regions, as well as the importance of the BotC, which contradicts previous physiological and pharmacological studies. To further evaluate the roles of synaptic inhibition and the BotC, we bilaterally microinjected the GABA(A) receptor antagonist gabazine and glycinergic receptor antagonist strychnine into the pre-BotC or BotC in anesthetized adult rats in vivo and in perfused in situ brainstem-spinal cord preparations from juvenile rats. Muscimol was microinjected to suppress neuronal activity in the pre-BotC or BotC. In both preparations, disrupting inhibition within pre-BotC or BotC caused major site-specific perturbations of the rhythm and disrupted the three-phase motor pattern, in some experiments terminating rhythmic motor output. Suppressing BotC activity also potently disturbed the rhythm and motor pattern. We conclude that inhibitory circuit interactions within and between the pre-BotC and BotC critically regulate rhythmogenesis and are required for normal respiratory motor pattern generation.