The role of catecholaminergic neurons in the ventrolateral medulla in the protective arousal response to hypoxia

Project: Research

Investigators

  • Stephen Bruce ABBOTT (PI)

Description

During sleep, acute hypoxia produces intense cardiorespiratory stimulation along with various degrees of cortical arousal. Arousal enhances protective autonomic reflexes and permits corrective behavior to reinstate breathing such as the freeing of airways. These protective mechanisms can also be detrimental to human health if they occur with excessive frequency, as seen in obstructive sleep apnea . Conversely, if protective arousal fails to occur, the result can be fatal, as seen in congenital central hypo-ventilation syndrome. The neural pathways responsible for arousal in response to hypoxia are poorly described. One candidate is the C1 neurons, which are catecholaminergic neurons that reside in the rostral half on the ventrolateral medulla. These neurons are a nodal point for efferent signaling for most cardio-respiratory reflexes, they are robustly activated by hypoxia and they innervate key wake-promoting brain regions.We will evaluate the possibility that increasing the activity of C1 neurons is capable of producing arousal in sleeping rodents. This question will be addressed using an optogenetic approach which will allow us to activate the C1 neurons selectively in unrestrained sleeping rats while recording EEG and neck muscle EMG. We will also investigate whether the C1 innervation of the wake-promoting neurons in the locus coeruelus subserves this potential function. This question will be addressed using an optogenetic approach which will allow us to activate the C1 neurons selectively in anesthetized rats while recording the activity of noradrenergic locus coeruleus neurons.This research will provide a meaningful impetus to current understanding of the mechanisms by which hypoxia causes both sleep disruption and cardiorespiratory stimulation and it should eventually contribute to a better treatment of sleep disordered breathing and its associated pathologies.
Award amount$82,000.00
Award date07/01/2011
Program typePostdoctoral Fellowship
Award ID11POST7170001
Effective start/end date07/01/201106/30/2013
StatusFinished