Kevin J. Cummings, Ph.D.

  • Associate Professor
  • PhD: University of Victoria (Prof. Nancy M Sherwood)

Email: cummingske@missouri.edu

Phone:
573-882-0283 (office)
573-882-0133 (lab)

 

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 sympathetic nerve activity and blood pressure regulation in adult animals.  Our published findings suggest that serotonin dysfunction may be an underlying cause of neurogenic hypertension.  Ongoing experiments are dedicated to resolving the central pathways underpinning the apparent inhibition provided by serotonin on sympathetic activity.

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.

We also investigate 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. Recently published data from our lab suggests that orexin plays a key role in maintaining breathing in infancy, possibly explaining the association between orexin system defects and SIDS. We have also recently revealed a novel role for orexin in the hypoxic ventilatory response (HVR). Current experiments are utilizing DREADD approaches to reveal the central nuclei in which orexin acts to facilitate the HVR.

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:

  1. 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 PMID: 30763168
  2. Magnusson, J.L., Emter, C.A. and Cummings, K.J. 2020. Sex- and age-based differences in the effect of central serotonin on arterial blood pressure regulation. J Appl Physiol 129: 1310-1323 PMID: 32909922
  3. Cummings, K.J. 2021. Eupnea and gasping in vivo are facilitated by the activation of 5-HT2A receptors. J Neurophys 125:1543-51 PMID: 33760672
  4. Spinieli, R., Ben Musa, R., Kielhofner, J.K., Cornelius-Green, J. and Cummings, K.J. 2021. Orexin contributed to eupnea within a critical period of postnatal development. Am J Physiol Regul Integr and Comp Physiol  in press. PMID: 34405704
  5. Spinieli, R., Ben Musa, R.,Cornelius-Green, J., Hasser, E.M, and Cummings, K.J. 2022. Orexin facilitates the ventilatory and behavioral responses of rats to hypoxia. Am J Physiol Regul Integr and Comp Physiol 1;322(6):R581-R596 PMID: 35380477