5 noradrenergic-projecting C1 neurons activate sympathetic and breathing outputs in anaesthetized rat

Autor(es)

Malheiros-Lima, Milene R. ^[1] ; Silva, Talita M. ^[1] ; Takakura, Ana C. ^[2] ; Moreira, Thiago S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Physiol & Biophys, Av Prof Lineu Prestes, 1524, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Pharmacol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Physiology; v. 107, n. 2 DEC 2021.
• Citações Web of Science: 1

Resumo

New Findings What is the central question of this study? C1 neurons innervate pontine noradrenergic cell groups, including the A5 region: do A5 noradrenergic neurons contribute to the activation of sympathetic and respiratory responses produced by selective activation of the C1 group of neurons. What is the main finding and its importance? The increase in sympathetic and respiratory activities elicited by selective stimulation of C1 neurons is reduced after blockade of excitatory amino acid within the A5 region, suggesting that the C1-A5 pathway might be important for sympathetic-respiratory control. Adrenergic C1 neurons innervate and excite pontine noradrenergic cell groups, including the ventrolateral pontine noradrenergic region (A5). Here, we tested the hypothesis that C1 activates A5 neurons through the release of glutamate and this effect is important for sympathetic and respiratory control. Using selective tools, we restricted the expression of channelrhodopsin2 under the control of the artificial promoter PRSx8 to C1 neurons (69%). Transduced catecholaminergic terminals within the A5 region are in contact with noradrenergic A5 neurons and the C1 terminals within the A5 region are predominantly glutamatergic. In a different group of animals, we performed retrograde lesion of C1 adrenergic neurons projecting to the A5 region with unilateral injection of the immunotoxin anti-dopamine beta-hydroxylase-saporin (anti-D beta H-SAP) directly into the A5 region during the hypoxic condition. As expected, hypoxia (8% O-2, 3 h) induced a robust increase in fos expression within the catecholaminergic C1 and A5 regions of the brainstem. Depletion of C1 cells projecting to the A5 regions reduced fos immunoreactivity induced by hypoxia within the C1 region. Physiological experiments showed that bilateral injection of kynurenic acid (100 mM) into the A5 region reduced the rise in mean arterial pressure, and sympathetic and phrenic nerve activities produced by optogenetic stimulation of C1 cells. In conclusion, the C1 neurons activate the ventrolateral pontine noradrenergic neurons (A5 region) possibly via the release of glutamate and might be important for sympathetic and respiratory outputs in anaesthetized rats. (AU)

• Processo FAPESP: 17/08696-5 - Sinalização purinérgica na região do Núcleo Retrotrapezóide: contribuição para o controle respiratório no modelo de epilepsia do lobo temporal
• Beneficiário: Milene Rodrigues Malheiros Lima
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/01236-4 - Efeitos de tratamentos farmacológicos e não farmacológicos nas alterações respiratórias observadas em um modelo murino da Doença de Parkinson
• Beneficiário: Ana Carolina Takakura Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/23376-1 - Núcleo retrotrapezóide, quimiossensibilidade central e automaticidade respiratória
• Beneficiário: Thiago dos Santos Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/12678-2 - Participação dos astrócitos localizados na superfície ventrolateral do bulbo nas respostas ventilatórias à hipercapnia e hipóxia
• Beneficiário: Talita de Melo e Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado