- PhD: University of Victoria (Prof. Nancy M Sherwood)
- Postdoctoral Training: University of Calgary (Prof. Richard JA Wilson); La Trobe University (Prof. Peter B Frappell); Dartmouth College (Prof. Eugene E Nattie)
Dalton Cardiovascular Research Center
134 Research Park Drive
Columbia, MO 652103
Our lab interested in how the central nervous system (CNS) controls breathing and cardiovascular function. Specifically, our NIH-funded research program investigates the role of serotonin and orexin neurons in respiratory and arterial blood pressure regulation in sleep and wakefulness. To do this we utilize novel methodologies to measure breathing, heart rate, arterial blood pressure and vigilance state in freely-behaving animals, focal application of drugs to specific nuclei of the CNS, and novel DREADD (designer receptors activated by designer drugs) technologies. Our ultimate goal is to resolve how defects in the serotonergic and orexinergic systems of the CNS make infants susceptible to Sudden Infant Death Syndrome (SIDS), a leading cause of infant death occurring during periods of sleep and involves acute and chronic cardiorespiratory dysfunction.
We have several on-going projects. We are studying the role of serotonin in the control of breathing and cardiovascular function in infancy, during wakefulness, REM and NREM sleep. Our recently published study shows that reduced brain stem serotonin leads to apnea (no breathing), as well as reduced blood pressure and bradycardia, phenotypes that appear specifically in REM or non-REM sleep. We are now attempting to resolve the mechanisms responsible for the state-dependency of serotonin’s effects on cardiorespiratory function in early life.
We are also investigating the role of serotonin in blood pressure regulation in adult animals, and our preliminary findings suggest that serotonin dysfunction may be an underlying cause of neurogenic hypertension. An associated project investigates the possibility that serotonin dysfunction contributes to some forms of heart failure, research that is being conducted in collaboration with Dr. Craig Emter.
We also study the role of serotonin in the coordinated cardiovascular, autonomic and respiratory responses to severe hypoxia, a process called “autoresuscitation”. Autoresuscitation allows young mammals to survive conditions of oxygen deprivation, and there is evidence that this process is defective in SIDS cases. Our lab has shown that infant animals lacking brain stem serotonin have compromised autoresuscitation, and we are currently investigating the underlying mechanisms by which serotonin acts to promote the autonomic and respiratory response to severe hypoxia that allow for autoresuscitation.
Finally, we have embarked on a new project exploring the role of orexin in the control of breathing during sleep and wakefulness, in both infant and adult animals. Orexin is a hypothalamic neuropeptide traditionally known for its role in keeping us awake. New data from our lab suggests that orexin plays a key role in maintaining breathing specifically in infancy, possibly explaining the association between orexin system defects and SIDS.
Our laboratory is located at the Dalton Cardiovascular Research Center, where we have active collaborations with other Investigators interested in the neural control of breathing, cardiovascular and autonomic function. If you are a highly-motivated person who is interested in joining our research team, I encourage you to get in touch with me by phone or email. Thanks for your interest in our research!
Recent publications demonstrating our interests and techniques:
- Davis, M.R., Magnusson, J.L. and Cummings, K.J. 2019. Increased central cholinergic drive contributes to the apneas of serotonin-deficient rat pups during active sleep. J Appl Physiol 126:1175-1183
- Magnusson, J.L. and Cummings, K.J. 2018. Central serotonin and the control of arterial blood pressure and heart rate in infant rats: influence of sleep state and sex. Am J Physiol Regul Integr and Comp Physiol Am J Physiol Regul Integr and Comp Physiol 314: R313-R321
- Young, J.O, J., Guerts, A., Hodges, M.R. and Cummings, K.J. 2017. Active sleep unmasks apnea and delayed arousal in infant rat pups lacking central serotonin. J Appl Physiol J Appl Physiol 123: 825-834 PMID: 28775068
- Givan, S.A., Cummings, K.J. 2016. Intermittent severe hypoxia and serotonin depletion induce cellular and transcriptomic plasticity in the neonatal rat ventrolateral medulla. J Appl Physiol 120: 1277-87. PMID: 26968026
- Magnusson, J., and Cummings, K.J. 2015. Plasticity in breathing and arterial blood pressure following acute intermittent hypercapnic hypoxia in infant rat pups with a partial loss of 5-HT neurons. Am J Physiol Regul Integr Comp Physiol 309:R1273-84. PMID:26354844