Gasping Generation in Developing Swiss–Webster Mice In Vitro and In Vivo

Peña, Fernando; Meza-Andrade, Roberto; Páez-Zayas, Victor; González-Marín, M.C.

doi:10.1007/s11064-008-9616-x

Cited by 23 publications

(54 citation statements)

References 33 publications

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“…The observed re-arrangements of network interactions among the respiratory elements is consistent with a previous report that a brief application of cyanide (chemical hypoxia) induced the retraction of neuronal processes of respiratory neurons, which was interpreted as a reduction in connectivity among respiratory neurons (Mironov, 2009). Moreover, this change in the strength of interactions within the respiratory network in hypoxia can be related to the uncoupling of preBötC activity from one of its motor outputs (the hypoglossal nucleus) during fictive-gasping generation (Ramirez et al, 1998; Peña et al, 2008). However, the activity of the phrenic nerve is also uncoupled from hypoglossal nerve activity in hypoxia, which may explain why, under hypoxic conditions, the amplitude of the phrenic output is not reduced (St-John et al, 2004; St. John and Leiter, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Details of the slice preparation have been previously reported (Peña et al, 2004, 2008). Briefly, animals were anesthetized and decapitated, and the brainstem was quickly removed and placed in ice-cold artificial cerebrospinal fluid (ACSF) constantly bubbled with carbogen (95% O2 and 5% CO2).…”

Section: Methodsmentioning

confidence: 99%

“…A single slice (550 μm thick; Peña and Ramirez, 2002) per animal was obtained and transferred into a recording chamber with a total volume of 2 ml and containing a MEA at the bottom (Multi-Channel Systems; Reutlingen, Germany; Figure 1A). There, the slice was continuously perfused by recirculating 200 ml ACSF at a flow rate of 10 ml/min and constantly bubbled with carbogen to ensure efficient oxygenation and exchange of the solution (Peña et al, 2004, 2008; Zavala-Tecuapetla et al, 2008, 2014). A temperature controller (Multi-Channel Systems; Reutlingen, Germany) maintained the temperature at 30 ± 1°C.…”

Section: Methodsmentioning

confidence: 99%

“…To allow long-term recordings of rhythmic population activity, extracellular KCl was elevated from 3 to 8 mM over a span of 75 min before starting the recordings (Tryba et al, 2003; Figure 1A). Hypoxic conditions were induced by removing carbogen and bubbling the ACSF for 15 min with 95% N2 and 5% CO2 (Peña et al, 2004, 2008 Figure 1A). Our experimental conditions are almost identical to those used and characterized by Hill et al (2011).…”

Section: Methodsmentioning

confidence: 99%

“…To evaluate the population burst pattern of preBötC activity we measured the peak-to-peak amplitude of the raw signal every 45 ms. By averaging the amplitude signals for several bursts, it is possible to clearly distinguish the changes in burst pattern occurring during the transition from fictive-eupnea to fictive-gasping (Figure 1A, inset; Lieske et al, 2000; Lieske and Ramirez, 2003; Peña et al, 2008) Recordings were pass-band filtered (250–7000 Hz) with MC_Rack Software (Multi-Channel Systems, Reutlingen, Germany). The channels exhibiting respiratory activity were selected (an average of 25 channels covering an area of 400 by 400 μm; Figure 1A; Carroll and Ramirez, 2013).…”

Section: Methodsmentioning

confidence: 99%

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Change in network connectivity during fictive-gasping generation in hypoxia: prevention by a metabolic intermediate

et al. 2014

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Change in network connectivity during fictive-gasping generation in hypoxia: prevention by a metabolic intermediate

et al. 2014

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The Cellular Building Blocks of Breathing

Ramirez

Doi

Garcia

et al. 2012

Comprehensive Physiology

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Respiratory brainstem neurons fulfill critical roles in controlling breathing: they generate the activity patterns for breathing and contribute to various sensory responses including changes in O2 and CO2. These complex sensorimotor tasks depend on the dynamic interplay between numerous cellular building blocks that consist of voltage-, calcium-, and ATP-dependent ionic conductances, various ionotropic and metabotropic synaptic mechanisms, as well as neuromodulators acting on G-protein coupled receptors and second messenger systems. As described in this review, the sensorimotor responses of the respiratory network emerge through the state-dependent integration of all these building blocks. There is no known respiratory function that involves only a small number of intrinsic, synaptic, or modulatory properties. Because of the complex integration of numerous intrinsic, synaptic, and modulatory mechanisms, the respiratory network is capable of continuously adapting to changes in the external and internal environment, which makes breathing one of the most integrated behaviors. Not surprisingly, inspiration is critical not only in the control of ventilation, but also in the context of “inspiring behaviors” such as arousal of the mind and even creativity. Far-reaching implications apply also to the underlying network mechanisms, as lessons learned from the respiratory network apply to network functions in general.

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Microglia modulate respiratory rhythm generation and autoresuscitation

Lorea-Hernández

Morales

Rivera-Angulo

et al. 2015

Glia

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Inflammation has been linked to the induction of apneas and Sudden Infant Death Syndrome, whereas proinflammatory mediators inhibit breathing when applied peripherally or directly into the CNS. Considering that peripheral inflammation can activate microglia in the CNS and that this cell type can directly release all proinflammatory mediators that modulate breathing, it is likely that microglia can modulate breathing generation. It might do so also in hypoxia, since microglia are sensitive to hypoxia, and peripheral proinflammatory conditions affect gasping generation and autoresuscitation. Here, we tested whether microglial activation or inhibition affected respiratory rhythm generation. By measuring breathing as well as the activity of the respiratory rhythm generator (the preBötzinger complex), we found that several microglial activators or inhibitors, applied intracisternally in vivo or in the recording bath in vitro, affect the generation of the respiratory rhythms both in normoxia and hypoxia. Furthermore, microglial activation with lipopolysaccharide affected the ability of the animals to autoresuscitate after hypoxic conditions, an effect that is blocked when lipopolysaccharide is co-applied with the microglial inhibitor minocycline. Moreover, we found that the modulation of respiratory rhythm generation induced in vitro by microglial inhibitors was reproduced by microglial depletion. In conclusion, our data show that microglia can modulate respiratory rhythm generation and autoresuscitation.

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Gasping Generation in Developing Swiss–Webster Mice In Vitro and In Vivo

Cited by 23 publications

References 33 publications

Change in network connectivity during fictive-gasping generation in hypoxia: prevention by a metabolic intermediate

Change in network connectivity during fictive-gasping generation in hypoxia: prevention by a metabolic intermediate

The Cellular Building Blocks of Breathing

Microglia modulate respiratory rhythm generation and autoresuscitation

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