Stephen Johnson

johnsons@svm.vetmed.wisc.edu

Department of Comparative Biosciences
Office: 4462

Education

• M.D., Medicine, 1990 University of Iowa
• Ph.D., Physiology 1990 University of Iowa
• M.S., Biochemistry 1982 University of California at Riverside
• B.A., Biochemistry 1981 University of California at Riverside

Research

Respiratory Rhythm Generation and Plasticity

Breathing is a rhythmic motor behavior produced throughout our entire lifetime, but how neurons in the brainstem generate this behavior is not known. We study isolated brainstems from hypoxia-resistant red-eared slider turtles because the brainstems produce expiratory and inspiratory activity for days under in vitro conditions. Currently, we are testing whether pacemaker neurons play a critical role in rhythm generation using multichannel recordings with silicon microelectrodes. Our major findings are that pacemaker neurons may not be required for respiratory rhythm generation.

Also, bath application of serotonergic and adrenergic drugs produces acute and long-lasting (plasticity) in the timing and clustering of respiratory-related bursting activity. Our major findings are that activation of 5-HT3 and alpha-1 adrenergic receptors increases respiratory burst frequency and reduces episodic breathing.

In addition to studies on isolated turtle brainstems, we are also characterizing how different drugs (e.g., opioids) alter breathing pattern in freely-swimming turtles. Our major findings are that mu-opioid receptor activation causes respiratory depression by decreasing breathing frequency.

• Majewski DM, Wiegel LM, Johnson SM. Respiratory pattern in midline-lesioned brainstems and hemibrainstems from adult turtles. Respir Physiol Neurobiol 164: 338-349, 2008.
   
• Johnson SM, Wiegel LM, Majewski DM. Are pacemaker properties required for respiratory rhythm generation in adult turtle brainstems in vitro? Am J Physiol Regul Integr Comp Physiol 293: R901-R910, 2007.
   
• Mitchell GS, Johnson SM. Invited Review: Neuroplasticity in respiratory motor control. J Appl Physiol 94: 358-374, 2003.
   
• Johnson SM, Wilkerson JER, Wenninger MR, Henderson DR, Mitchell GS. Role of synaptic inhibition in turtle respiratory rhythm generation. J Physiol (Lond) 544: 253-265, 2002.
   
• Johnson SM, Wilkerson JER, Henderson DR, Wenninger MR, Mitchell GS. Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brainstems in vitro. J Appl Physiol 91: 2703-2712, 2001.
   

Delta Opioid Receptor Dependent Neuroprotection

Ischemia during the time of birth is the leading cause of neurological disorders in children. Delta opioid receptor (DOR) activation appears to be a highly conserved (observed in hypoxia-resistant turtles and hibernating ground squirrels) mechanism that protects neurons and other tissues during oxygen-glucose deprivation (OGD). Using neonatal rat brainstem-spinal cord preparations, our major findings are that DOR activation prior to, during, and after onset of spinal OGD protects spinal motoneurons and prolongs spontaneous respiratory motor output.

Current experiments are testing whether DOR dependent neuroprotection occurs in other parts of the brain and whether the magnitude of the neuroprotection increases with development.

Microfluidic Chambers: Controlling Neuronal Microenvironment In Vitro

In collaboration with Dr. Justin Williams (Biomedical Engineering, UW-Madison), our goal is to develop novel microfluidic chambers that allow solutions to be precisely delivered to brain slices or isolated brainstems. Current experiments are determining the factors that regulate how substances penetrate and diffuse within the brain tissue.

• Blake AJ, Pearce TM, Rao NS, Johnson SM, Williams JC. Multilayer PDMS microfluidic chamber for controlling slice microenvironment. Lab on a Chip 7: 842-849, 2007.

Reptile Analgesia Without Respiratory Depression

In collaboration with Dr. Kurt Sladky (Surgical Sciences, UW School of Vet Med), our goal is to test and develop pharmacological approaches for providing pain relief in reptiles with minimal or no respiratory depression. To test for analgesic effects of drugs, noxious thermal stimuli are applied to the hindlimbs of awake turtles before and after drug administration. Breathing in freely-swimming turtles is measured as described above to measure any respiratory depression.

Our major findings are that butorphanol (most widely prescribed drug for pain relief in reptiles) does not provide analgesia, while morphine provides analgesia and causes severe respiratory depression.

Current studies show that tramadol given orally produces long-lasting analgesia (up to 3 days after drug administration) with only modest respiratory depression.

• Sladky KK, Kinney ME, Johnson SM. Mu-opioid (MOR) activation provides antinociception in red-eared slider turtles (Trachemys scripta). Am J Vet Res (in press).
   
• Johnson SM, Kinney ME, Wiegel LM. Inhibitory and excitatory effects of mu (MOR), delta (DOR), and kappa (KOR) opioid receptor activation on breathing in awake turtles (Trachemys scripta). Am J Physiol Regul Integr Comp Physiol 295: R1599-R1612, 2008.
   
• Sladky KK, Kinney ME, Johnson SM. Analgesic efficacy of butorphanol and morphine in bearded dragons (Pogona vitticeps) and corn snakes (Elaphe guttata). J Am Vet Med Assoc 233: 267-273, 2008.
   
• Sladky KK, Miletic V, Paul-Murphy J, Kinney M, Dallwig R, Johnson SM. Analgesic efficacy and respiratory effects of butorphanol and morphine in turtles (Trachemys scripta). J Am Vet Med Assoc 230: 1356-1362, 2007. 

VISIT THE JOHNSON LAB

Responsibilities

Associate Professor

• Principles of Vertebrate Physiology
• Veterinary Physiology

Graduate Training

• Comparative Biomedical Sciences Training Program
• Neuroscience Training Program

Recent Publications

Mitchell GS, Johnson SM. Invited Review: Neuroplasticity in respiratory motor control. J Appl Physiol 94: 358-374, 2003. [Abstract]

Fuller DD, Johnson SM, Olson EB, Mitchell GS. Synaptic pathways to phrenic motoneurons are enhanced by chronic intermittent hypoxia following cervical spinal cord injury. J Neurosci 23: 2993-3000, 2003. [Abstract]

Johnson SM, Wilkerson JER, Wenninger MR, Henderson DR, Mitchell GS. Role of synaptic inhibition in turtle respiratory rhythm generation. J Physiol (Lond) 544: 253-265, 2002. [Abstract]

Johnson SM, Wilkerson JER, Henderson DR, Wenninger MR, Mitchell GS. Serotonin elicits long-lasting enhancement of rhythmic respiratory activity in turtle brainstems in vitro. J Appl Physiol 91: 2703-2712, 2001. [Abstract]

Johnson SM, Mitchell GS. Activity-dependent plasticity of descending synaptic inputs to spinal respiratory motoneurons in an in vitro turtle brainstem-spinal cord preparation. J Neurosci 20: 3487-3495, 2000. [Abstract]