Respiratory Rhythm Generation and Plasticity, Neuroprotection
Office Phone: (608) 263-2996, (608) 263-5013
Coupling and Reconfiguration of Rhythmic Motor Networks
Neural networks that generate behaviors, such as walking and breathing, are hypothesized to consist of coupled rhythmic motor networks that undergo reconfiguration to produce different motor behaviors (i.e., multifunctional). In collaboration with Dr. Justin Williams (UW Dept of Biomedical Engineering), our goal is to determine how coupling and reconfiguration in mammalian rhythmic motor networks contribute to behavior. Currently, we are constructing a versatile research tool called a ‘microfluidic chamber’ to study neurophysiology in brain slices in vitro. Microfluidic chambers permit high spatiotemporal control of slice extracellular space in combination with multichannel recording via multielectrode arrays. Rhythmically active medullary slices cut from neonatal rat brainstems are being used because they contain rhythmic respiratory-related, synaptically-coupled motor networks (i.e., preBötzinger Complex [preBötC]) located bilaterally in the ventrolateral medulla. Acquiring mechanistic systems-level information on rhythmic motor networks may lead to therapeutic insights for treating pathological conditions affecting rhythmic networks, such as stroke, spinal cord injury, cerebral palsy, Parkinson’s disease, etc.
Mechanisms of Respiratory Rhythm Generation
Our goal is to understand how the vertebrate respiratory rhythm is generated at the cellular, synaptic and network levels. Turtles were chosen as the animal model because, as reptiles, they represent an important phylogenetic intermediate between mammals and lower vertebrates. The central hypothesis is that the chelonian respiratory rhythm is produced by multiple interconnected brainstem oscillatory networks that are driven by a specific subclass of respiratory neurons with endogenous pacemaker properties. It is important to understand how respiratory activity is produced because breathing is required for life and principles underlying network organization and mechanisms may apply to other rhythmic motor networks controlling locomotion, chewing and swallowing.
Respiratory Frequency Plasticity
Long-term changes in frequency (i.e., frequency plasticity) may enable animals to adapt to various physiological and pathophysiological conditions. We recently developed an in vitro model of breathing frequency plasticity in an adult vertebrate to study underlying cellular mechanisms. In isolated turtle brainstems, bath-applied phenylbiguanide (PBG, 5-HT3 receptor agonist) increases respiratory frequency and causes a long-lasting (>2 hr) frequency increase that persists during drug washout. Currently, we are investigating the pharmacology of chelonian respiratory frequency plasticity and testing whether adrenergic receptor activation induces similar frequency plasticity.
- Johnson S.M., L.M. Wiegel, and D.M. Majewski. 2007. Are pacemaker properties required for respiratory rhythm generation in adult turtle brainstems in vitro? Am. J. Physiol. Regul. Integr. Comp. Physiol. In press
- Blake A.J., T.M. Pearce, N.S. Rao, S.M. Johnson, and J.C. Williams. 2007. Multilayer PDMS microfluidic chamber for controlling slice microenvironment. Lab Chip 7: 842-849
- Sladky K.K., V. Miletic, J. Paul-Murphy, M. Kinney, R. Dallwig, and S.M. Johnson. Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles (Trachemys scripta). J. Am. Vet. Med. Assoc. 230: 1356-1362
- Lovett-Barr M.R., G.S. Mitchell, I. Satriotomo, and S.M. Johnson. 2006. Serotonin-induced in vitro long-term facilitation exhibits differential pattern sensitivity in cervical and thoracic inspiratory motor output. Neuroscience 142: 885-892
- Johnson S.M., and R.J. Creighton. 2005. Spinal cord injury-induced changes in breathing are not due to supraspinal plasticity in turtles (Pseudemys). Am. J. Physiol. Regul. Integr. Comp. Physiol. 289: R1550-R1561
- Fuller, D.D., S.M. Johnson, E.B. Olson, and G.S. Mitchell. 2003. Synaptic pathways to phrenic motoneurons are enhanced by chronic intermittent hypoxia following cervical spinal cord injury. J. Neurosci. 23: 2993-3000.
- Mitchell G.S. and S.M. Johnson. 2003. Neuroplasticity in respiratory motor control. J. Appl. Physiol. 94: 358-374.
- Johnson, S.M., G.S. Mitchell. 2002. Activity-dependent plasticity in descending synaptic inputs to respiratory spinal motoneurons. Respir. Physiol. Neurobiol. 131: 79-90.
- Johnson, S.M., J.E.R. Wilkerson, M.R.Wenninger, D.R. Henderson, and G.S. Mitchell. 2002. Role of synaptic inhibition in turtle respiratory rhythm generation. J. Physiol. (Lond) 544: 253-265.
- Johnson, S.M., J.E.R. Wilkerson, D.R. Henderson, M.R.Wenninger, G.S. Mitchell. 2001. Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brainstems in vitro. J. Appl. Physiol. 91: 2703-2712.