Neuronal network properties underlying the generation of gasping

Abstract

1. The pre-Bötzinger complex (PreBötC) generates different inspiratory rhythms. Under control normoxic conditions, a mixture of intrinsic and synaptic properties underlies the generation of eupnoea by the PreBötC. Under hypoxia, those network properties change and modify the respiratory rhythm pattern. Hypoxia can be caused by a reduction in oxygen availability in the environment, inadequate oxygen transport, an inability of tissues to use oxygen or several pathological conditions. 2. During severe hypoxia, the network properties within the PreBötC are reconfigured whereby the network no longer generates eupnoea, but instead generates a new rhythm, named gasping. Such reconfiguration includes changes in synaptic and intrinsic properties triggered by hypoxia itself, as well as the influence of different neuromodulators released during hypoxia. Gasping has been considered an important arousal mechanism that triggers autoresuscitation. Dysregulation of gasping has been proposed to result in failure to autoresuscitate and has been hypothesised to contribute to Sudden Infant Death Syndrome. 3. Precisely which synaptic and/or neuronal intrinsic membrane properties are critical to central respiratory rhythmogenesis, in either normoxia or hypoxia, is still the subject of considerable debate. In the present article I review how hypoxia alters the respiratory network and discuss my hypotheses regarding the cellular and network mechanisms involved in gasping rhythm generation. Finally, I review changes in the hypoxic response during postnatal development and the contribution of several neuromodulators to such a response.

Pacemaker Neurons and Neuronal Networks in Health and Disease

“…Respiratory rhythm commands are generated by two, interacting oscillators, one controlling inspiration (preBötC) and other, located in the parafacial respiratory group (pFRG), possibly controlling active expiration [76][77][78][79]. Neurons with pacemaker properties have been identified in the preBötC [5,80,81; Fig.…”

Possible Role or Respiratory Pacemaker Neurons in the Generation of Different Breathing Patterns

“…Breathing is commanded and regulated by the respiratory centres of the brainstem (Richter, 1982;Bianchi et al, 1995;Feldman, 1995). The central respiratory pattern generator consists of two interacting oscillators, one controlling inspiration (the pre-Bötzinger complex; PreBötC) and other, located in the parafacial respiratory group (pFRG), possibly controlling active expiration (Smith et al, 1991;Onimaru & Homma, 2006;Janczewski & Feldman, 2006;Peña, 2009). In contrast with the pFRG, the vital role of the PreBötC in the generation of respiratory rhythms is supported by a variety of experimental data.…”

“…Another seems to be the scenery during gasping generation. As previously mentioned, the PreBötC undergoes a reconfiguration process during hypoxia to generate gasping (Lieske et al 2000;Peña, 2009). Three major changes occur during hypoxic conditions in this network:…”

“…Indeed, failure to respond to severe hypoxia via gasping and autoresuscitation can result in death. Thus, dysregulation of the generation of gasping rhythm and/or autoresuscitation has been hypothesised to contribute to Sudden Infant Death Syndrome (SIDS; Poets et al, 1999;Sridhar et al, 2003;Peña, 2009). Breathing is commanded and regulated by the respiratory centres of the brainstem (Richter, 1982;Bianchi et al, 1995;Feldman, 1995).…”

“…Ventilation of the lungs as consequence of rhythmic contractions of the respiratory muscles constitutes a complex neuromuscular function that involves several brainstem and spinal cord circuits, several muscles such as the diaphragm, intercostal, laryngeal and pharyngeal muscles, as well as the lungs and the vasculature (Richter, 1982;Bianchi et al, 1995;Feldman, 1995) A reduction in such function can cause hypoxia, that evokes a response of the respiratory network that leads to the generation of gasping, which is considered to be the 'last-resort' respiratory effort to autoresuscitate and sustain life (Poets et al, 1999;Sridhar et al, 2003;Peña, 2009). Indeed, failure to respond to severe hypoxia via gasping and autoresuscitation can result in death.…”