Development and Mechanism of Oxygen Sensitivity in Caudal Hypothalamic Neurons

The goals of the studies described in this thesis were to elucidate the development of the hypoxic responses of rat caudal hypothalamic neurons and to determine the specific membrane properties responsible for these responses. Male Sprague-Dawley rats aged postnatal day 3 (P3) through P56 were exposed to hypoxia for a period of 3 hours. When compared to their normoxic counterparts, the rats exposed to hypoxia displayed a significant increase in the density of caudal hypothalamic neurons expressing the protein Fos. This increase, however, was not apparent until P12 and continued throughout P56. Peripheral chemoreceptor input was not required for this increase since a similar increase in the density of Fos protein induced by hypoxia was observed following section of the carotid sinus nerves in a subset of rats. Similarly, caudal hypothalamic neurons from more mature rats were more likely to respond to a brief period of hypoxia when compared to cells from immature rats in a brain slice preparation. The response of these cells to hypoxia was a depolarization and increased firing frequency that was due to a sustained inward current. Interestingly, this inward current response was no different in magnitude between neurons from immature and mature rats. Pharmacological analyses demonstrated that this inward current response was due to sodium and not calcium current. This sodium current was then studied in greater detail in acutely dissociated caudal hypothalamic neurons from mature rats. Whole-cell patch clamp recordings determined that both the fast-inactivating and persistent sodium current were significantly increased during hypoxia in these neurons. Taken together, hypoxia activates caudal hypothalamic neurons in conscious rats throughout development in a manner consistent with the development of the respiratory responses to hypoxia. This activation involves an inward current that is prevalent in a greater portion of mature caudal hypothalamic neurons. Enhancement of two types of sodium current is the likely mechanism of this hypoxia-induced inward current and most likely underlies the depolarization and increased firing frequency observed in these cells during hypoxia. This developmental activation of caudal hypothalamic neurons likely modulates the development of the respiratory responses to hypoxia.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Horn, Eric Michael

Contributors dc:contributor

• Waldrop, Tony G.

• Biology, Animal Physiology

Language dc:language

eng

Identifier

(MiAaPQ)AAI9971099

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/82542