Nicole L. Nichols, PhD

  • NICHOLS_NicoleAssistant Professor
  • Investigator, Dalton Cardiovascular Research Center
  • PhD: Wright State University
  • Postdoctoral Training: University of Wisconsin-Madison (Prof. Gordon S. Mitchell)
  • Teaching: Multi-Disciplinary Approaches to Biomedical Sciences, Neural Control of the Circulation, Veterinary Microanatomy, Veterinary Endocrinology and Reproductive Physiology
  • Contact:

Email: nicholsn@missouri.edu
Office: Veterinary Medicine Building W145
Lab: Veterinary Medicine Building W146-W151
Phone: 573-882-2534 (office); 573-882-3715 (lab)

 

Understanding how plasticity can be enhanced in models of motor neuron death to restore breathing

Our laboratory focuses on the central nervous system, in particular the control of breathing in models of motor neuron death. Breathing is essential to life and cannot cease for more than the briefest periods, or life will not continue. At the same time, breathing must be continuously adjusted throughout life to maintain homeostasis in response to physiological (for example exercise, pregnancy or high altitude) or pathological (for example disease or disorder) situations. One way the neural system controlling breathing maintains homeostasis is to express plasticity which is defined as a persistent change in the neural control system based on a prior experience. A well-known model of respiratory plasticity is phrenic long-term facilitation (pLTF), a long-lasting increase in phrenic motor output elicited by acute exposure to intermittent hypoxia. Although, we know a great deal about the mechanism that underlies pLTF under normal circumstances, the mechanism that underlies pLTF in models of motor neuron death is not well understood. Determining the mechanism that underlies pLTF and how it can be enhanced in models of motor neuron death to restore breathing is the focus of the laboratory.

We utilize a multidisciplinary approach to elucidate these mechanisms. These include: 1) novel pharmacological injections to induce models of motor neuron death; 2) whole animal plethysmography to measure respiration in unanesthetized animals; 3) in vivo neurophysiology to measure spontaneous nerve output and nerve output in response to targeted drug delivery; and 4) immunohistochemical localization of neurotransmitter receptors and proteins of interest on individual neurons, astrocytes and microglia. Using these techniques, we have recently developed a novel model of motor neuron death that mimics aspects of ALS (amyotrophic lateral sclerosis) related to ventilatory function. Further, using this model, we can study the mechanism that underlies pLTF and how this plasticity can be enhanced following motor neuron death.

  1. Nichols, N.L., Satriotomo, I., Harrigan, D.J. and Mitchell, G.S. (2015). Acute intermittent hypoxia induced phrenic long-term facilitation despite increased SOD1 expression in a rat model of ALS. Exper. Neurol. 273: 138-150.
  2. Nichols, N.L., Vinit, S., Bauernschmidt, L. and Mitchell, G.S. (2015). Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections. Exper. Neurol. 267: 18-29.
  3. Nichols, N.L., Johnson, R.A., Satriotomo, I. and Mitchell, G.S. (2014). Neither serotonin nor adenosine-dependent mechanisms preserve ventilatory capacity in ALS rats. Respir. Physiol. Neurobiol. 197: 19-28.
  4. Huxtable, A.G., MacFarlane, P.M., Vinit, S., Nichols, N.L., Dale, E.A. and Mitchell, G.S. (2014). Adrenergic a1 receptor activation is sufficient, but not necessary for phrenic long-term facilitation. J. Appl. Physiol. 116(11): 1345-1352.
  5. Nichols, N.L. and Sasser, J.M. (2014). The other side of the submit button: how to become a reviewer for scientific journals. Physiologist. 57(2): 88-91.
  6. Nichols, N.L., Powell, F.L., Dean, J.B. and R.W. Putnam. (2014). Substance P differentially modulates firing rate of solitary complex (SC) neurons from control and chronic hypoxia-adapted adult rats. PLoS ONE. 9(2): e88161.
  7. Nichols, N.L., Van Dyke, J., Suzuki, M. and Mitchell, G.S. (2013). Ventilatory control in ALS. Respir. Physiol. Neurobiol. 183(2): 429-437.
  8. Devinney, M.J., Huxtable, A.G., Nichols, N.L. and Mitchell, G.S. (2013). Hypoxia-induced phrenic long-term facilitation: emergent properties. Ann. N Y Acad. Sci. 1279(1): 143-153.
  9. Nichols, N.L., Gowing, G., Satriotomo, I., Nashold, L.J., Dale, E.A., Suzuki, M., Avalo, P., Mulcrone, P.L., McHugh, J., Svendsen, C.N. and Mitchell, G.S. (2013). Intermittent hypoxia and stem cell implants preserve breathing capacity in a rodent model of ALS. Am. J. Resp. Crit. Care Med. 187(5): 535-542.
  10. Nichols, N.L., Punzo, A.M., Duncan, I.D., Mitchell, G.S. and Johnson, R.A. (2013). Cervical spinal demyelination with ethidium bromide impairs respiratory (phrenic) activity and forelimb motor behavior in rats. Neuroscience 229: 77-87.
  11. Strey, K.A., Nichols, N.L., Baertsch, N., Broytman, O. and Baker-Herman, T.L. (2012). Spinal atypical protein kinase C activity is necessary to stabilize inactivity-induced phrenic motor facilitation. J. Neurosci. 32(46): 16510-16520.
  12. Hoffman, M.S., Nichols, N.L., Macfarlane, P.M. and Mitchell, G.S. (2012). Phrenic long term facilitation following acute intermittent hypoxia requires spinal ERK activation but not TrkB synthesis. J. Appl. Physiol. 113(8): 1184-1193.
  13. Nichols, N.L., Dale, E.A. and Mitchell, G.S. (2012). Severe acute intermittent hypoxia elicits phrenic long-term facilitation by a novel adenosine-dependent mechanism. J. Appl. Physiol. 112(10): 1678-1688.
  14. Nichols, N.L., Wilkinson, K.A., Powell, F.L. and Putnam R.W. (2009). Chronic hypoxia suppresses the CO2 response of solitary complex (SC) neurons from rats. Respir. Physiol. Neurobiol.168(3): 272-280.
  15. Nichols, N.L., Mulkey, D.K., Wilkinson, K.A., Powell, F.L., Dean J.B. and Putnam R.W. (2009). Characterization of the chemosensitive response of individual solitary complex (SC) neurons from adult rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296(3): 763-773.
  16. Conrad, S.C., Nichols, N.L., Ritucci, N.A., Dean, J.B. and Putnam R.W. (2009). Development of chemosensitivity in neurons from the nucleus tractus solitarii (NTS) of neonatal rats. Respir. Physiol. Neurobiol.166(1): 4-12.
  17. Nichols, N.L., Hartzler, L.K., Conrad, S.C., Dean, J.B. and R.W. Putnam. (2008). Intrinsic chemosensitivity of individual nucleus tractus solitarius (NTS) and locus coeruleus (LC) neurons from neonatal rats. Adv. Exp. Med. Biol. 605: 348-352.