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 two 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, retinoic acid and atypical PKC 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, 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.
- Fundamental Principles of Veterinary Anatomy
Neuroscience Training Program
Comparative Biomedical Training Program
Physiology Graduate Training Program
- Baertsch NA, Baker TL (2017). Reduced respiratory neural activity elicits a long-lasting decrease in the CO2 threshold for apnea in anesthetized rats. Exp Neurol. Jan;287(Pt 2):235-242.
- Braegelmann KM, Streeter KA, Fields DP, Baker TL (2017). Plasticity in respiratory motor neurons in response to reduced synaptic inputs: A form of homeostatic plasticity in respiratory control? Exp Neurol. Jan;287(Pt 2):225-234.
- Baertsch N, Baker-Herman TL (2015). Intermittent respiratory neural inactivity elicits spinal TNFα-independent, atypical PKC-dependent phrenic motor facilitation. Am J Physiol-Reg I. 308(8):R700-7.
- Streeter KA, Baker-Herman TL (2014). Spinal NMDA receptor activation constrains inactivity-induced phrenic motor facilitation in Charles River Sprague Dawley rats. J Appl Physiol 117:682-93. PMCID: PMC4187051
- Streeter KA, Baker-Herman TL (2014). Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation. Exp Neurol 256:46-56.
- Strey KA, Baertsch NA, Baker-Herman TL (2013). Inactivity-induced respiratory plasticity: protecting the drive to breathe in disorders that reduce respiratory neural activity. Respir Physiol Neurobiol 189:384-95. PMCID: PMC3898815.
- Broytman O, Baertsch NA, Baker-Herman TL (2013). Spinal TNFα is necessary and sufficient for inactivity-induced phrenic motor facilitation. J Physiol 591:5585-98. PMCID: PMC3853497.
- Baertsch NA and Baker-Herman TL (2013). Inactivity-induced phrenic motor facilitation (iPMF) is more efficiently induced by intermittent than sustained periods of neural apnea. J Appl Physiol 114(10):1388-95. PMCID: PMC3656425.
- Strey KA, Nichols NL, Baertsch NA, Broytman O, Baker-Herman TL (2012). Spinal atypical protein kinase C activity is necessary to stabilize inactivity-induced phrenic motor facilitation. J Neurosci 32(46):16510-20.
- Baker-Herman TL, Strey KA (2011). Similarities and differences in mechanisms of phrenic and hypoglossal motor facilitation. Respir Physiol Neurobiol 179:48-56.
- Mahamed S, Strey KA, Mitchell GS, Baker-Herman TL (2011). Reduced respiratory neural activity elicits phrenic motor facilitation. Respir Physiol Neurobiol 175(3):303-9.