Hypothalamic and medullary modulation of cardiorespiratory responses to hypoxia and hypercapnia

The role of ventrolateral medullary and caudal hypothalamic neurons in the cardiorespiratory response to hypoxia and hypercapnia was examined. Initial experiments performed on anesthetized rats demonstrated that microinjection into the rostral ventrolateral medulla (VLM) of the excitatory amino acid receptor antagonist kynurenic acid resulted in increased respiratory activity and enhanced respiratory responses to hypoxic and hypercapnic stimuli. Microinjections just caudal, however, typically resulted in apnea. The results suggest that excitatory amino acid transmission in the rostral VLM exerts a tonic inhibitory effect on respiratory activity and responses to hypoxia and hypercapnia. In contrast, excitatory amino acid transmission further caudal in the VLM may be required for the maintenance of respiratory activity. Remaining experiments used in vivo and in vitro preparations to examine responses of caudal hypothalamic neurons to hypoxia and hypercapnia. Hypothalamic single unit activity, phrenic nerve activity, and cervical sympathetic nerve activity were recorded in anesthetized cats. Caudal hypothalamic neurons were likely to be stimulated by hypoxia or hypercapnia, but seldom both stimuli. Computer averaging techniques showed that neurons responsive to these stimuli were more likely than unresponsive neurons to have a discharge related to cardiovascular and/or respiratory activity. Similar results were found in barodenervated, peripherally-chemodenervated cats. The results suggest separate subpopulations of caudal hypothalamic neurons modulate cardiorespiratory responses to hypoxia and hypercapnia. A brain slice preparation was subsequently used in an attempt to determine if caudal hypothalamic neurons are inherently responsive to hypoxia and hypercapnia. In addition, experiments were performed to determine if these types of neurons possess distinct electrophysiological and morphological properties. Results demonstrated that a large percentage of caudal hypothalamic neurons are stimulated by hypoxia in a reduced preparation; the majority of these retain their responsiveness when synaptic transmission is blocked, indicating they are inherently chemoresponsive and may be central hypoxia-sensitive chemoreceptors. A second, distinct population of caudal hypothalamic neurons is inherently responsive to hypercapnia; these neurons may function as traditional central chemoreceptors. Finally, it was found that hypoxia-stimulated, hypercapnia-stimulated, and unstimulated neurons possess several distinct electrophysiological and morphological properties. These properties may relate to how these types of neurons respond to a hypoxic or hypercapnic challenge.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Molecular and Integrative Physiology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Dillon, Glenn Haley

Contributors dc:contributor

• Waldrop, Tony G.

• Biology, Neuroscience
• Biology, Animal Physiology

Statement dc:rights

• Copyright 1993 Dillon, Glenn Haley

Language dc:language

eng

Identifier

AAI9329015
(UMI)AAI9329015

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/22701