Measurement and State-dependent Modulation of the Excitability of a Brainstem Motoneuron Pool In-Vivo

Measuring the excitability of a central motoneuron pool in-vivo across behavioural states to identify mechanisms of control is difficult, and accordingly studies are few. Here I applied ‘optogenetics’ to optically control genetically targeted motoneurons in mice and determine their net excitability from measures of motor output. I applied this tool to a motor circuit critical to the pathogenesis of obstructive sleep apnea (OSA). OSA is caused by airway closure in sleep due to relaxation of tongue muscles. The hypoglossal motoneuron pool (HMN) is the source of motor output to the tongue, and strategies to measure and modulate its activity are needed to identify and test new pharmacological treatments for OSA. This thesis identifies that (1) an optogenetic protocol can be used to measure the endogenous excitability of the HMN in-vivo, and (2) endogenous HMN excitability is significantly reduced in rapid eye movement (REM) sleep compared to non-REM sleep and wakefulness.M.Sc