Hyperexcitability and plasticity induced by sustained hypoxia on rectus abdominis motoneurons

Author(s)

da Silva, Melina P. ^[1] ; Moraes, Davi Jose A. ^[1] ; Bonagamba, Leni G. H. ^[1] ; Mecawi, Andre de Souza ^[2] ; Varanda, Wamberto A. ^[1] ; Machado, Benedito H. ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Fed Sao Paulo, Paulista Sch Med, Dept Biophys, Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF PHYSIOLOGY-LONDON; v. 597, n. 7, p. 1935-1956, APR 2019.
• Web of Science Citations: 0

Abstract

Key points Acute hypoxia induces active expiration in rectus abdominis (RA) muscles in conscious freely moving rats, although its overall contribution is smaller than in internal oblique (IO) muscles. Tonically active and silent RA motoneurons were identified in in vitro preparations of rat spinal cords. Sustained hypoxia (SH) increased the synaptic strength and induced morphological changes in tonically active RA motoneurons. Expiratory RA motoneurons were recorded in the in situ preparation and SH enhanced both the excitability and the synaptic transmission in those firing during the stage 2 expiration. The present study contributes to a better understanding of the mechanisms involved in SH recruitment of RA motoneurons to induce active expiration in rats. Rectus abdominis (RA) motoneurons translate the complex respiratory brainstem inputs into effective muscle contractions. Despite their fundamental role in respiration, their functional and morphological properties are not fully understood. In the present study, we investigated for the first time the contribution of RA muscle to active expiration and characterized RA motoneurons regarding their electrical, molecular and morphological profiles in control rats and in rats submitted to sustained hypoxia (SH), which induces chronic recruitment of abdominal muscles. Electromyographic experiments in conscious freely moving control rats and SH rats showed that RA contributes to active expiration induced by acute hypoxia, although its contribution is smaller than in internal oblique muscles. in vitro whole-cell patch clamp recordings from RA motoneurons revealed two populations of cells: tonically active and silent. SH induced hyperexcitability in the tonically active cells by changing their action potential properties, and EPSCs. Three-dimensional morphological reconstructions of these cells showed that SH increased the dendritic complexity, stimulated the appearance of dendrite spines, and increased the somatic area and volume. Physiologically identified RA motoneurons, firing in two distinct phases of expiration, were recorded in the brainstem-spinal cord in situ preparation of rats. SH increased the firing frequency and EPSCs of neurons firing during stage 2 expiration. Taken together, our results show that RA motoneurons reconfigure their biophysical properties, morphology and synaptic strength to produce an appropriate expiratory drive in response to SH in rats. (AU)

• FAPESP's process: 13/06077-5 - Changes in the neural networks involved with the generation and control of sympathetic and respiratory activities in different experimental models of hypoxia
• Grantee: Benedito Honorio Machado
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/10484-5 - Electrophysiological and molecular characterization of neurons involved in the generation of respiratory rhythm and pattern of rats during postnatal development
• Grantee: Davi José de Almeida Moraes
• Support Opportunities: Research Grants - Young Investigators Grants