In vivo and in vitro responses of neurons in the ventrolateral medulla to hypoxia

Abstract

Neurons in the ventrolateral medulla (VLM) are known to be involved in several cardiorespiratory reflexes and to provide tonic drive to sympathetic preganglionic neurons. Recent studies have suggested that VLM neurons modulate the respiratory responses to hypoxia and to hypercapnia. The purpose of the present study was to determine with electrophysiological techniques if the discharge of these neurons is altered by hypoxia and/or by hypercapnia both in vivo and in vitro. Extracellular single-unit activity of VLM neurons ( n = 39) was recorded during inhalation of a hypoxic gas (10% O 2) and during inhalation of a hypercapnic gas (5% CO 2) in anesthetized, spontaneously breathing rats ( n = 16). Hypoxia elicited an increase in the discharge frequency in 64% of the VLM neurons studied; hypercapnia stimulated 42% of the neurons. Fifty-two percent of the neurons were stimulated by both hypoxia and hypercapnia. Signal averaging revealed that 76% of the hypoxia-stimulated neurons had a resting discharge related to the cardiac and/or respiratory cycle. Similar percentages of VLM neurons (35/54) were stimulated by hypoxia in a second group of animals ( n = 14) that were studied after sinoaortic denervation. A rat brain slice preparation was then used to determine if hypoxia exerts a direct effect upon neurons in the VLM. Perfusing a hypoxic gas over the surface of medullary slices evoked an increase in the discharge frequency in the majority (39/49) of VLM neurons studied; responses were graded in relation to the magnitude of the hypoxic stimulus. Similar responses to hypoxia were observed in VLM neurons studied during perfusion with a synaptic blockade medium. Retrograde labeling of VLM neurons with rhodamine tagged microspheres injected into the thoracic intermediolateral cell column demonstrated that the hypoxia sensitive neurons were located in a region of the VLM that projects to the thoracic spinal cord. These results demonstrate that neurons in the ventrolateral medulla are excited by a direct effect of hypoxia; these neurons may play a critical role in the cardiorespiratory responses to hypoxia.