Poster Title

Exploring Approaches to Promote Respiratory Motor Plasticity Through Varied and Fixed Interval Intermittent Hypoxia

Grade Level at Time of Presentation

Senior

Major

Neuroscience

Minor

Violin Performance

2nd Grade Level at Time of Presentation

Senior

2nd Student Major

Psychology

Institution

University of Kentucky

KY House District #

75

KY Senate District #

13

Department

Dept. of Neuroscience, College of Medicine

Abstract

In the human population, spinal cord injury (SCI) most commonly occurs at the cervical level. Interruptions of descending pathways here can result in breathing motor deficits through paralysis of the diaphragm, sometimes necessitating mechanical ventilation for survival which greatly decreases patients’ quality of life. Fixed interval intermittent hypoxia (FIH) treatment is utilized in rat models to attenuate breathing motor deficits resulting from cervical SCI. FIH consists of the repeated, alternating exposure of a subject to consistent and equal durations of hypoxic and normoxic conditions. Specifically, this treatment induces a prolonged increase in phrenic motor output, a type of respiratory motor plasticity known as phrenic Long Term Facilitation. FIH exhibits similarity to the psychological construct of operant conditioning in which the increased incidence and persistence of a desired, spontaneous behavior is trained through reinforcement. As such, each interval of hypoxia can be construed as the period during which the subject responds with heightened respiratory drive and is subsequently reinforced by an interval of normoxia. Provided that FIH procedure is a form of operant conditioning, it can be optimized. Using the fixed or variable duration of the hypoxic interval as our independent variable, we hypothesize that Varied Interval Hypoxia (VIH) treatment will induce a greater, more prolonged increase in phrenic motor output than FIH. To test this hypothesis, we utilized electromyographic recording to assess our dependent variable of diaphragmatic activity. Rats treated by VIH after C2 Hemisection injury exhibited diaphragmatic output achieving 33.87±7.29% of maximum induced by nasal occlusion, compared to 19.20±5.63% in FIH treated animals. These data suggest that VIH may induce greater recovery than FIH after injury, though this trend is insignificant by unpaired t-test (p=0.1588). Further exploration will focus on timepoint of treatment post injury and on the greater optimization of FIH using ratio schedules of normoxic reinforcement.

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Exploring Approaches to Promote Respiratory Motor Plasticity Through Varied and Fixed Interval Intermittent Hypoxia

In the human population, spinal cord injury (SCI) most commonly occurs at the cervical level. Interruptions of descending pathways here can result in breathing motor deficits through paralysis of the diaphragm, sometimes necessitating mechanical ventilation for survival which greatly decreases patients’ quality of life. Fixed interval intermittent hypoxia (FIH) treatment is utilized in rat models to attenuate breathing motor deficits resulting from cervical SCI. FIH consists of the repeated, alternating exposure of a subject to consistent and equal durations of hypoxic and normoxic conditions. Specifically, this treatment induces a prolonged increase in phrenic motor output, a type of respiratory motor plasticity known as phrenic Long Term Facilitation. FIH exhibits similarity to the psychological construct of operant conditioning in which the increased incidence and persistence of a desired, spontaneous behavior is trained through reinforcement. As such, each interval of hypoxia can be construed as the period during which the subject responds with heightened respiratory drive and is subsequently reinforced by an interval of normoxia. Provided that FIH procedure is a form of operant conditioning, it can be optimized. Using the fixed or variable duration of the hypoxic interval as our independent variable, we hypothesize that Varied Interval Hypoxia (VIH) treatment will induce a greater, more prolonged increase in phrenic motor output than FIH. To test this hypothesis, we utilized electromyographic recording to assess our dependent variable of diaphragmatic activity. Rats treated by VIH after C2 Hemisection injury exhibited diaphragmatic output achieving 33.87±7.29% of maximum induced by nasal occlusion, compared to 19.20±5.63% in FIH treated animals. These data suggest that VIH may induce greater recovery than FIH after injury, though this trend is insignificant by unpaired t-test (p=0.1588). Further exploration will focus on timepoint of treatment post injury and on the greater optimization of FIH using ratio schedules of normoxic reinforcement.