Inhibitory control of active expiration by the Botzinger complex in rats

Autor(es)

Flor, Karine C. ^[1] ; Barnett, William H. ^[2] ; Karlen-Amarante, Marlusa ^[1] ; Molkov, I, Yaroslav ; Zoccal, Daniel B. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ, Sch Dent Araraquara, Dept Physiol & Pathol, UNESP, Rua Humaita 1680, BR-14801903 Araraquara, SP - Brazil

^[2] I, Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PHYSIOLOGY-LONDON; v. 598, n. 21 JUL 2020.
• Citações Web of Science: 3

Resumo

Key points Contraction of abdominal muscles at the end of expiration during metabolic challenges (such as hypercapnia and hypoxia) improves pulmonary ventilation. The emergence of this active expiratory pattern requires the recruitment of the expiratory oscillator located on the ventral surface of the medulla oblongata. Here we show that an inhibitory circuitry located in the Botzinger complex is an important source of inhibitory drive to the expiratory oscillator. This circuitry, mediated by GABAergic and glycinergic synapses, provides expiratory inhibition that restrains the expiratory oscillator under resting condition and regulates the formation of abdominal expiratory activity during active expiration. By combining experimental and modelling approaches, we propose the organization and connections within the respiratory network that control the changes in the breathing pattern associated with elevated metabolic demand. The expiratory neurons of the Botzinger complex (BotC) provide inhibitory inputs to the respiratory network, which, during eupnoea, are critically important for respiratory phase transition and duration control. Here, we investigated how the BotC neurons interact with the expiratory oscillator located in the parafacial respiratory group (pFRG) and control the abdominal activity during active expiration. Using the decerebrated, arterially perfusedin situpreparations of juvenile rats, we recorded the activity of expiratory neurons and performed pharmacological manipulations of the BotC and pFRG during hypercapnia or after the exposure to short-term sustained hypoxia - conditions that generate active expiration. The experimental data were integrated in a mathematical model to gain new insights into the inhibitory connectome within the respiratory central pattern generator. Our results indicate that the BotC neurons may establish mutual connections with the pFRG, providing expiratory inhibition during the first stage of expiration and receiving excitatory inputs during late expiration. Moreover, we found that application of GABAergic and glycinergic antagonists in the BotC caused opposing effects on abdominal expiratory activity, suggesting complex inhibitory circuitry within the BotC. Using mathematical modelling, we propose that the BotC network organization and its interactions with the pFRG restrain abdominal activity under resting conditions and contribute to abdominal expiratory pattern formation during active expiration observed during hypercapnia or after the exposure to short-term sustained hypoxia. (AU)

• Processo FAPESP: 18/21000-2 - Mecanismos iônicos recrutados durante a resposta ventilatória ao ATP: entendendo a interação entre sensores centrais para oxigênio e os neurônios geradores do ritmo respiratório
• Beneficiário: Daniel Breseghello Zoccal
• Modalidade de apoio: Bolsas no Exterior - Pesquisa
• Processo FAPESP: 15/23568-8 - Controle inibitório do padrão de expiração ativa em ratos submetidos à hipóxia crônica
• Beneficiário: Karine Correa Flor
• Modalidade de apoio: Bolsas no Brasil - Mestrado