Breathing responses produced by optogenetic stimulation of adrenergic C1 neurons are dependent on the connection with preBotzinger complex in rats

Autor(es)

Malheiros-Lima, Milene R. ^[1] ; Totola, Leonardo T. ^[1] ; Lana, Marlous V. G. ^[2] ; Strauss, Bryan E. ^[2] ; Takakura, Ana C. ^[3] ; Moreira, Thiago S. ^[1]

Afiliação do(s) autor(es)

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

^[2] Univ Sao Paulo, Sch Med, Canc Inst Sao Paulo, Ctr Translat Invest Oncol, LIM24, BR-01246000 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY; v. 470, n. 11, p. 1659-1672, NOV 2018.
• Citações Web of Science: 4

Resumo

Optogenetic stimulation of the adrenergic C1 neurons produces cardiorespiratory activation, and selective depletion of these cells attenuates breathing responses induced by hypoxia. The preBotzinger complex (preBotC) is a group of neurons located in the intermediate aspect of the ventrolateral medulla, critical for respiratory rhythmogenesis, and is modulated by glutamate and catecholamines. Our hypothesis is that selective activation of C1 neurons leads to breathing responses by excitatory connections with the preBotC neurons. Anatomical connection between C1 cells and preBotC was evaluated using retrograde (Cholera Toxin b; preBotC) and anterograde (LVV-PRSx8-ChR2-eYFP; C1 region) tracers. LVV-PRSx8-ChR2-eYFP (viral vector that expresses channelrhodopsin-2 (ChR2) under the control of the catecholaminergic neuron-preferring promoter (PRSx8) was also injected into the C1 region of male Wistar rats for the functional experiments. Anatomical results demonstrated that preBotC neurons receive projections from C1 cells, and these projections express tyrosine hydroxylase and vesicular glutamate transporter 2. Functional connection between C1 cells and preBotC was evaluated by photostimulation of ChR2-transduced C1 neurons before and after unilateral injection of the ionotropic glutamate antagonist, kynurenic acid (kyn), or cocktail of adrenergic antagonists in the preBotC. Kyn injection into preBotC blocked the increase in Dia(EMG) frequency without changing the MAP increase elicited by photostimulation of C1 neurons, while the injection of adrenergic antagonists into the preBotC did not change Dia(EMG) frequency and MAP increase induced by photostimulation of C1 cells. Our results suggest that the increase in breathing produced by photostimulation of C1 neurons can be caused by a direct glutamatergic activation of preBotC neurons. (AU)

• Processo FAPESP: 14/07698-6 - Envolvimento dos neurônios catecolaminérgicos do bulbo ventrolateral rostral no controle da atividade respiratória
• Beneficiário: Milene Rodrigues Malheiros Lima
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• 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: 16/23281-3 - Regiões encefálicas responsáveis pela neuroplasticidade observada na resposta respiratória induzida por hipercapnia em modelo animal de Doença de Parkinson
• Beneficiário: Ana Carolina Takakura Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/22069-0 - Melhora nos mecanismos de regulação do fluxo sanguíneo encefálico em animais espontaneamente hipertensos: participação do exercício físico
• Beneficiário: Thiago dos Santos Moreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular