Education

• Ph.D. Neuroscience Training Program, University of Wisconsin-Madison, 2001

• M.S. in Biology, University of Texas at Arlington, 1997

• B.S. in Biology, University of Texas at Arlington, 1994

Research

The primary focus of the Baker-Herman laboratory is to understand mechanisms of plasticity in the respiratory control system. The neural circuits giving rise to breathing must be stable enough to produce an effective pattern of respiratory muscle activation, yet be plastic enough to accommodate ever-changing physiological and environmental conditions as an animal grows, matures and ages. Our research focuses on determining how respiratory motor neurons adjust to persistent changes in descending drive from brainstem networks generating breathing to enable optimal levels of ventilation. We focus on three primary areas of research:

Homeostatic synaptic plasticity of respiratory motor output

 In normal animals, the pattern of respiratory muscle activation remains largely the same throughout development, from birth until old age. Yet, the excitability of the neurons driving breathing may change dramatically throughout life, as changes occur in cell size, intrinsic excitability, dendritic field, synaptic number or synaptic strength. How does the respiratory control system maintain the appropriate pattern and strength of respiratory muscle activation in the face of continual physiological and environmental pressures that alter neuronal excitability? The hypothesis guiding our efforts in this direction is that local negative feedback mechanisms sense respiratory motor neuron activity and adjust synaptic efficacy to maintain motor output within an optimal range. This “self-tuning” ability may stabilize neural output in the face of internal and external perturbations while preserving the capacity for plasticity.

Current research efforts are directed at understanding the role of glial-derived TNFa and all-trans retinoic acid synthesis within respiratory motor neurons in homeostatic regulation of respiratory motor output. This research has direct implications for understanding compensatory mechanisms that help to preserve respiratory motor output following the onset ventilatory control disorders (i.e, obstructive sleep apnea, neurodegenerative disease, spinal injury), and may identify promising therapeutic targets to restore ventilation when endogenous mechanisms of plasticity are insufficient.

Recovery of respiratory motor output following spinal injury 

Our goal is to use endogenous mechanisms of plasticity to elicit functional recovery of respiratory motor output following spinal injury. The fundamental hypothesis guiding our efforts in this direction is that disruption of descending inspiratory drive to phrenic motor neurons following spinal injury initiates homeostatic increases in synaptic efficacy designed to “ramp up” phrenic motor output. When spinal injuries are incomplete, these homeostatic mechanisms may strengthen spared pathways and/or reveal previously silent crossed phrenic pathways. Other forms of respiratory plasticity, such as long-term facilitation following intermittent hypoxia, may then be used to further strengthen these residual pathways, thereby leading to a partial functional recovery of ventilation following high cervical spinal injuries.  

Ventilatory control following prenatal alcohol exposure

Infants exposed to ethanol during gestation may develop Fetal Alcohol Spectrum Disorder (FASD). Infants with FASD have an increased risk for catastrophic health disorders, such as sudden death syndrome (SIDS). However, very little is known regarding the effects of early chronic ethanol exposure on the control of breathing in any model system. We are investigating the mechanisms that underlie long-term deficits in the ventilatory control system following developmental ethanol exposure.

Responsibilities

Assistant Professor

• Fundamental Principles of Veterinary Anatomy

Recent Publications

 Baker-Herman TL, Mitchell GS (2008). Determinants of frequency long-term facilitation following acute intermittent hypoxia in vagotomized rats. Respir. Physiol. & Neurobiol. 162:8-17. (Abstract)

 Golder FJ, Ranganathan L, Satriotomo I, Hoffman M, Baker-Herman TL, Watters JJ, Mitchell GS (2008). A2a receptors transactivate cervical spinal TrkB receptors and improve respiratory function following cervical spinal injury. J Neurosci 28:2033-42. (Abstract)

 Wilkerson JER, MacFarlane PM, Satriotomo I, Baker-Herman TL, Mitchell GS (2008). Okadaic acid-sensitive protein phosphatases constrain phrenic long-term facilitation following sustained hypoxia. J Neurosci. 28:2949-58. (Abstract)

 Fuller DD, Baker-Herman TL, Golder FJ, Doperalski NJ, Watters JJ, Mitchell GS (2005). Cervical Spinal Cord Injury Upregulates Ventral Spinal 5-HT(2A) Receptors. J Neurotrauma 22:203-13. (Abstract)

 Golder FJ, Zabka AG, Bavis RW, Baker-Herman T, Fuller DD, Mitchell GS (2005). Differences in time-dependent hypoxic phrenic responses among inbred rat strains. J Appl Physiol 98:838-44. (Abstract)

 Baker-Herman TL, Fuller DD, Bavis RW, Zabka AG, Golder FJ, Doperalski NJ, Johnson RA, Watters JJ, Mitchell GS (2004). BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia. Nat Neurosci 7:48-55. (Abstract)

 Baker-Herman TL, Mitchell GS (2002). Phrenic long-term facilitation requires spinal serotonin receptor activation and protein synthesis. J Neurosci 22:6239-46. (Abstract)

 Baker TL, Fuller DD, Zabka AG, Mitchell GS (2001). Respiratory plasticity: differential actions of continuous and episodic hypoxia and hypercapnia. Respir Physiol 129:25-35.  (Abstract)

 Fuller DD, Baker TL, Behan M, Mitchell GS (2001). Expression of hypoglossal long-term facilitation differs between sub-strains of Sprague-Dawley rat. Physiol Genomics 4:175-181. (Abstract)

 Fuller DD, Zabka A, Baker TL, Mitchell GS (2001). Physiological and Genomic Consequences of Intermittent Hypoxia: Selected Contribution: Phrenic long-term facilitation requires 5-HT receptor activation during but not following episodic hypoxia. J Appl Physiol 90:2001-2006. (Abstract)

 Mitchell GS, Baker TL, Nanda SA, Fuller DD, Zabka AG,. Hodgeman BA, Bavis RW, Mack KJ, Olson EB, Jr (2001). Physiological and Genomic Consequences of Intermittent Hypoxia: Invited Review: Intermittent hypoxia and respiratory plasticity. J Appl Physiol 90:2466-2475. (Abstract)

 Baker TL, Mitchell GS (2000). Episodic but not continuous hypoxia elicits long-term facilitation of phrenic motor output in rats. J Physiol 529:215-219. (Abstract)