Lateral parafacial region neurons: electrophysiological characteristics, active expiration generation and modulation of sympathetic activity and cardiovascular function

Author(s)

Karolyne Silva Magalhães

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2024-02-28

Examining board members

Davi José de Almeida Moraes; Luiz Guilherme de Siqueira Branco; Thiago dos Santos Moreira; Daniel Breseghello Zoccal

• Advisor: Davi José de Almeida Moraes

Abstract

Active expiration is essential to increase pulmonary ventilation during increased respiratory demand (hypercapnia). Several studies have shown that the lateral parafacial region (pFL), which contains expiratory neurons, controls the activity of the abdominal muscles during active expiration in response to hypercapnia. However, the electrophysiological properties and synaptic mechanisms that determine the activity of expiratory neurons in the pFL region, as well as the specific conditions for their activity, are not fully understood. Using whole-cell patch clamp and single-cell qRT-PCR techniques, we describe the intrinsic electrophysiological properties, phenotype and respiratory-related synaptic inputs to the expiratory neurons of the pFL region, as well as the mechanisms for the expression of their expiratory activity under conditions of hypercapnia-induced active expiration, in in situ preparations of young rats. We also evaluated whether these neurons have intrinsic CO2/[H+] sensitivity and intrinsic burst-generating properties. GABAergic and glycinergic inhibition during inspiration and expiration suppress the activity of expiratory glutamatergic neurons in the pFL region in normocapnia. In hypercapnia, these neurons escape from glycinergic inhibition and generate bursts at the end of expiration. We present evidence of the contribution of post-inhibitory rebound, the CaV3.2 isoform of T-type Ca2+ channels and intracellular [Ca2+]. Intrinsic burst properties, mediated by persistent Na+ current, CO2/[H+] sensitivity or expression of CO2/[H+] sensitive ion channels/receptors (TASK or GPR4) were not observed. On the other hand, currents mediated by hyperpolarization-activated or cyclic nucleotide-gated channels and leak channels for K+ were recorded. Postsynaptic disinhibition and the intrinsic electrophysiological properties of glutamatergic neurons play important roles in the generation of expiratory oscillations in the pFL region during hypercapnia in rats. (AU)

• FAPESP's process: 19/24060-9 - Contribution of the parafacial Respiratory Group to the inspiratory, expiratory and cardiovascular responses of rats to muscle afferent fiber stimulation
• Grantee: Karolyne Silva Magalhães
• Support Opportunities: Scholarships in Brazil - Doctorate