Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México Querétaro, México.
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México México D.F., México.
Front Physiol. 2014 Jul 23;5:265. doi: 10.3389/fphys.2014.00265. eCollection 2014.
The neuronal circuit in charge of generating the respiratory rhythms, localized in the pre-Bötzinger complex (preBötC), is configured to produce fictive-eupnea during normoxia and reconfigures to produce fictive-gasping during hypoxic conditions in vitro. The mechanisms involved in such reconfiguration have been extensively investigated by cell-focused studies, but the actual changes at the network level remain elusive. Since a failure to generate gasping has been linked to Sudden Infant Death Syndrome (SIDS), the study of gasping generation and pharmacological approaches to promote it may have clinical relevance. Here, we study the changes in network dynamics and circuit reconfiguration that occur during the transition to fictive-gasping generation in the brainstem slice preparation by recording the preBötC with multi-electrode arrays and assessing correlated firing among respiratory neurons or clusters of respiratory neurons (multiunits). We studied whether the respiratory network reconfiguration in hypoxia involves changes in either the number of active respiratory elements, the number of functional connections among elements, or the strength of these connections. Moreover, we tested the influence of isocitrate, a Krebs cycle intermediate that has recently been shown to promote breathing, on the configuration of the preBötC circuit during normoxia and on its reconfiguration during hypoxia. We found that, in contrast to previous suggestions based on cell-focused studies, the number and the overall activity of respiratory neurons change only slightly during hypoxia. However, hypoxia induces a reduction in the strength of functional connectivity within the circuit without reducing the number of connections. Isocitrate prevented this reduction during hypoxia while increasing the strength of network connectivity. In conclusion, we provide an overview of the configuration of the respiratory network under control conditions and how it is reconfigured during fictive-gasping. Additionally, our data support the use of isocitrate to favor respiratory rhythm generation under normoxia and to prevent some of the changes in the respiratory network under hypoxic conditions.
负责产生呼吸节律的神经元回路位于 Pre-Bötzinger 复合体（preBötC）中，在常氧条件下配置为产生虚拟呼吸，在体外缺氧条件下重新配置为产生虚拟喘息。通过细胞聚焦研究广泛研究了这种重新配置的机制，但网络水平的实际变化仍难以捉摸。由于未能产生喘息与婴儿猝死综合征（SIDS）有关，因此研究喘息的产生和促进其产生的药理学方法可能具有临床意义。在这里，我们通过使用多电极阵列记录脑干切片中的 preBötC，并评估呼吸神经元或呼吸神经元簇（多单位）之间的相关放电，来研究在向虚拟喘息产生过渡期间网络动力学和电路重新配置的变化。我们研究了呼吸网络在缺氧时的重新配置是否涉及活跃呼吸元件的数量、元件之间功能连接的数量或这些连接的强度的变化。此外，我们测试了异柠檬酸对呼吸网络配置的影响，异柠檬酸是一种三羧酸循环中间体，最近已被证明可促进呼吸，在常氧条件下和缺氧条件下测试其对 preBötC 电路重新配置的影响。我们发现，与基于细胞聚焦研究的先前建议相反，在缺氧期间，呼吸神经元的数量和整体活性仅略有变化。然而，缺氧会降低电路内功能连接的强度，而不会减少连接的数量。异柠檬酸可防止缺氧期间这种减少，同时增加网络连接的强度。总之，我们提供了在对照条件下呼吸网络配置的概述，以及在虚拟喘息期间如何重新配置。此外，我们的数据支持使用异柠檬酸在常氧下促进呼吸节律产生，并防止缺氧条件下呼吸网络的一些变化。
