Morphological Characterization of Respiratory Neurons in the Pre-Bötzinger Complex

Zavala-Tecuapetla, Cecilia; Tapia, Dagoberto; Rivera-Angulo, Ana Julia; Galarraga, Elvira; Peña‐Ortega, Fernando

doi:10.1016/b978-0-444-63274-6.00003-5

Cited by 13 publications

(12 citation statements)

References 61 publications

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“…We suggest that the reduction in one or several of these microglia‐released modulators, upon microglia inhibition or depletion, might be affecting respiratory rhythm generation (Hutchinson et al, ; Peña‐Ortega, ). We base this hypothesis on the evidence that BDNF (Bouvier et al, ), glutamate (Peña and Ramirez, ; Zavala‐Tecuapetla et al, ), D‐serine (Beltran‐Castillo et al, ), ATP (Zwicker et al, ), hydrogen peroxide (Garcia et al, ), nitric oxide (Pyatin and Miroshnichenko, ), histamine (Dutschmann et al, ), and prostaglandin E2 (Koch et al, ) are either required for or favor respiratory rhythm generation (Peña and García, ; Peña‐Ortega, 2102).…”

Section: Discussionmentioning

confidence: 99%

“…The signal was amplified and filtered (low pass, 0.25 KHz; high pass, 5 Hz) using a wide‐band AC amplifier (Grass Instruments, Quincy, MA). The signal was also rectified and integrated by using an electronic filter (time constant of 30‐50 ms; designed by JFI electronics at The University of Chicago (Zavala‐Tecuapetla et al, 2008, ). The experimental protocol consisted of 30 min of basal recording, followed by bath application of different drugs as independent experiments.…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Microglia modulate respiratory rhythm generation and autoresuscitation

Lorea-Hernández

Morales

Rivera-Angulo

et al. 2015

Glia

Self Cite

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“…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%

“…Several neural circuits produce spontaneous synchronous activity through the interactions of the intrinsic properties of their neurons and the chemical and electrical synapses that link them into assemblies and networks (Ramirez et al, 2004; Carrillo-Reid et al, 2008; Peña, 2009; Jaidar et al, 2010; Zavala-Tecuapetla et al, 2014). Neuronal assembly bursting is an important feature that ensures the reliability of synaptic transmission, plasticity, and information processing (Lisman, 1997).…”

Section: Introductionmentioning

confidence: 99%

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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“…In many previous studies, inspiratory-modulated neurons in the preBötC were assumed to be excitatory in nature because they lacked neurotransmitter identification (Smith et al, 1991;Del Negro et al, 2002;Picardo et al, 2013;Zavala-Tecuapetla et al, 2014). Recently, the structural-functional properties of neurotransmitter-identified inspiratory neurons have been characterized (St-John et al, 2009;Koizumi et al, 2013).…”

Section: Morphological Features Of Prebötc Glycinergic Neuronsmentioning

confidence: 99%