GABAergic neurons of the medullary raphe regulate active expiration during hypercapnia

Author(s)

Silva, Josiane do N. ^[1] ; Oliveira, Luiz M. ^[1] ; Souza, Felipe C. ^[1] ; Moreira, Thiago S. ^[2] ; Takakura, Ana C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Farmacol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Neurophysiology; v. 123, n. 5, p. 1933-1943, MAY 2020.
• Web of Science Citations: 0

Abstract

The parafacial respiratory group (pFRG), located in the lateral aspect of the rostroventral lateral medulla, has been described as a conditional expiratory oscillator that emerges mainly in conditions of high metabolic challenges to increase breathing. The convergence of inhibitory and excitatory inputs to pFRG and the generation of active expiration may be more complex than previously thought. We hypothesized that the medullary raphe, a region that has long been described to be involved in breathing activity, is also responsible for the expiratory activity under hypercapnic condition. To test this hypothesis. we performed anatomical and physiological experiments in urethane-anesthetized adult male Wistar rats. Our data showed anatomical projections from serotonergic (5-HT-ergic) and GABAergic neurons of raphe magnus (RMg) and obscurus (ROb) to the pFRG region. Pharmacological inhibition of RMg or ROb with muscimol (60 pmo1/30 nL) did not change the frequency or amplitude of diaphragm activity and did not generate active expiration. However, under hypercapnia (9-10% CO2), the inhibition of RMg or ROb increased the amplitude of abdominal activity, without changing the increased amplitude of diaphragm activity. Depletion of serotonergic neurons with saporin anti-SERT injections into ROb and RMg did not increase the amplitude of abdominal activity during hypercapnia. These results show that the presumably GABAergic neurons within the RMg and ROb may be the inhibitory source to modulate the activity of pFRG during hypercapnia condition. NEW \& NOTEWORTHY Medullary raphe has been involved in the inspiratory response to central chemoreflex; however, these reports have never addressed the role of raphe neurons on active expiration induced by hypercapnia. Here, we showed that a subset of GABA cells within the medullary raphe directly project to the parafacial respiratory region, modulating active expiration under high levels of CO2. (AU)

• FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/23281-3 - Encephalic regions responsible for neuroplasticity observed in respiratory response induced by hypercapnia in a modelo of Parkinson's Disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/23418-3 - Anatomical characterization of the source of inhibition of neurons in the nucleus retrotrapezóide involved in the control of active expiration
• Grantee: Josiane do Nascimento Silva
• Support Opportunities: Scholarships in Brazil - Doctorate