Adrianne Huxtable

Assistant Professor, Department of Human Physiology
Member, ION

Ph.D. University of Alberta
B.Sc. University of British Columbia

huxtable@uoregon.edu
Lab Website
Office: 111 Pacific Hall
Phone: 541-346-9057

 

Overview: Research in the Huxtable laboratory focuses on the neural control of breathing (the central brainstem and spinal cord networks), with a specific focus on how inflammation (throughout the body and/or brain) undermines breathing. Breathing is a “simple”, rhythmic motor behaviour essential to maintaining life and homeostasis of blood gases (oxygen and carbon dioxide). The respiratory system begins generating episodic breathing rhythms in the womb and more regular rhythms abruptly at birth to begin exchange of blood gases, where it remains active until death. Despite the necessary robustness of the system, it is not a hardwired, immutable system even in adulthood. The respiratory system must be plastic (learn from previous experiences) and adapt to changes in state (sleep, wake), activity, aging, and disease or injury. The goal of Huxtable laboratory is to understand how the unstable respiratory network of premature or newborn infants are affected by inflammation, which commonly occurs with illness, infection, injury, and during the normal birthing process. Additionally, Dr. Huxtable’s research has shown a vulnerability of respiratory plasticity (a long-term change in respiratory motor output) in adults to inflammation. The current focus of the lab now is on whether inflammation during the perinatal period alters long-term respiratory network function and motor plasticity into adulthood. Research in the Huxtable laboratory combines concepts from neuroscience, respiratory physiology, and the immune system to answer basic science questions.

Dr. Huxtable currently has undergraduate, graduate and postdoctoral positions open in her laboratory and is happy to discuss research opportunities with interested trainees.

RECENT PUBLICATIONS

Related Articles

Time and dose-dependent impairment of neonatal respiratory motor activity after systemic inflammation.

Respir Physiol Neurobiol. 2019 Oct 12;:103314

Authors: Morrison NR, Johnson SM, Hocker AD, Kimyon RS, Watters JJ, Huxtable AG

Abstract
Neonatal respiratory impairment during infection is common, yet its effects on respiratory neural circuitry are not fully understood. We hypothesized that the timing and severity of systemic inflammation is positively correlated with impairment in neonatal respiratory activity. To test this, we evaluated time- and dose-dependent impairment of in vitro fictive respiratory activity. Systemic inflammation (induced by lipopolysaccharide, LPS, 5⿿mg/kg, i.p.) impaired burst amplitude during the early (1⿿h) inflammatory response. The greatest impairment in respiratory activity (decreased amplitude, frequency, and increased rhythm disturbances) occurred during the peak (3⿿h) inflammatory response in brainstem-spinal cord preparations. Surprisingly, isolated medullary respiratory circuitry within rhythmic slices showed decreased baseline frequency and delayed onset of rhythm only after higher systemic inflammation (LPS 10⿿mg/kg) early in the inflammatory response (1⿿h), with no impairments at the peak inflammatory response (3⿿h). Thus, different components of neonatal respiratory circuitry have differential temporal and dose sensitivities to systemic inflammation, creating multiple windows of vulnerability for neonates after systemic inflammation.

PMID: 31614211 [PubMed - as supplied by publisher]

Viral Mimetic-Induced Inflammation Abolishes Q-Pathway, but Not S-Pathway, Respiratory Motor Plasticity in Adult Rats.

Front Physiol. 2019;10:1039

Authors: Hocker AD, Huxtable AG

Abstract
Inflammation arises from diverse stimuli eliciting distinct inflammatory profiles, yet little is known about the effects of different inflammatory stimuli on respiratory motor plasticity. Respiratory motor plasticity is a key feature of the neural control of breathing and commonly studied in the form of phrenic long-term facilitation (pLTF). At least two distinct pathways can evoke pLTF with differential sensitivities to bacterial-induced inflammation. The Q-pathway is abolished by bacterial-induced inflammation, while the S-pathway is inflammation-resistant. Since viral-induced inflammation is common and elicits distinct temporal inflammatory gene profiles compared to bacterial inflammation, we tested the hypothesis that inflammation induced by a viral mimetic (polyinosinic:polycytidylic acid, polyIC) would abolish Q-pathway-evoked pLTF, but not S-pathway-evoked pLTF. Further, we hypothesized Q-pathway impairment would occur later relative to bacterial-induced inflammation. PolyIC (750 μg/kg, i.p.) transiently increased inflammatory genes in the cervical spinal cord (3 h), but did not alter medullary and splenic inflammatory gene expression, suggesting region specific inflammation after polyIC. Dose-response experiments revealed 750 μg/kg polyIC (i.p.) was sufficient to abolish Q-pathway-evoked pLTF at 24 h (17 ± 15% change from baseline, n = 5, p > 0.05). However, polyIC (750 μg/kg, i.p.) at 3 h was not sufficient to abolish Q-pathway-evoked pLTF (67 ± 21%, n = 5, p < 0.0001), suggesting a unique temporal impairment of pLTF after viral-mimetic-induced systemic inflammation. A non-steroidal anti-inflammatory (ketoprofen, 12.5 mg/kg, i.p., 3 h) restored Q-pathway-evoked pLTF (64 ± 24%, n = 5, p < 0.0001), confirming the role of inflammatory signaling in pLTF impairment. On the contrary, S-pathway-evoked pLTF was unaffected by polyIC-induced inflammation (750 μg/kg, i.p., 24 h; 72 ± 25%, n = 5, p < 0.0001) and was not different from saline controls (65 ± 32%, n = 4, p = 0.6291). Thus, the inflammatory-impairment of Q-pathway-evoked pLTF is generalizable between distinct inflammatory stimuli, but differs temporally. On the contrary, S-pathway-evoked pLTF is inflammation-resistant. Therefore, in situations where respiratory motor plasticity may be used as a tool to improve motor function, strategies targeting S-pathway-evoked plasticity may facilitate therapeutic outcomes.

PMID: 31456699 [PubMed]