Project Summary Studies in neurophysiology have historically excluded female participants. This has resulted in a well encompassing understanding of the neural control of movement in males, and a poor understanding of mechanisms underlying motor control differences in females. There is great need to study female motor physiology, as many neurological diseases progress differently between the sexes. In recent years, studies that have included adequate numbers of female participants have found motoneuronal discharge patterns and neuromuscular fatigue differ between the sexes but the mechanisms underlying these differences are unknown. Descending monoaminergic input from brainstem nuclei provide and modify motoneuronal discharge and is broadly understudied in the motor system. Our lab, however, has developed robust methods to quantify these monoaminergic influences on motoneuron discharge in humans. Thus, to understand if monoaminergic input is responsible for sex differences in motoneuron properties, I will indirectly quantify the amount of monoaminergic input to motoneurons in females and males. Motor commands consist of excitation, inhibition, and a lesser known neuromodulatory component that result in their subsequent discharge and activation of innervated muscle fibers. Neuromodulation is induced by release of two monoamines, serotonin and norepinephrine, from the brainstem to the spinal cord, which substantially alter discharge patterns of motoneurons. Sex hormones have extensive effects on many physiological systems in the human body and differ between the sexes. Females have levels of estradiol and progesterone that fluctuate regularly across the menstrual cycle and these fluctuations are associated with aspects motor control, including motoneuron discharge rates and fatigue. Additionally, neurons throughout the body, including the brainstem and spinal cord, contain estradiol and progesterone receptors. This suggests that fluctuating sex hormones may impact motoneuron function, but, again, underlying mechanisms have not been studied. Thus, to accurately assess sex differences in motoneuron discharge, hormonal cycles must be considered. I will use surface EMG arrays to quantify motoneuron discharge patterns during voluntary isometric contractions to determine 1) if monoaminergic input to motoneurons differs between males and females, and 2) whether motoneuron discharge patterns fluctuate across the menstrual cycle in females. This study will assess whether the amount of monoaminergic input motoneurons receive differs between the sexes to test a possible explanation for known sex differences, while also assessing other aspects of motoneuron discharge. Whether or not these studies identify sex-differences, findings from this work will not only further the scientific knowledge of how these sex hormones influence nervous system function but will highlight the critical importance for additional studies focusing on female participants out of need, necessity, and equity.

Project Narrative The study proposed in this application exhibits substantial promise to quantify motoneuron physiology in the underrepresented population of females and identify a mechanism behind sex differences in motoneuron discharge. Additionally, this is the first quantitative study to examine motoneuron discharge properties across the menstrual cycle. The proposed paradigm is positioned to increase knowledge on female motoneuron physiology, and aid in the understanding of what causes sex differences in the progression of neurological disease.