PROJECT SUMMARY/ABSTRACT
CANDIDATE: Dr. Streeter’s career objective is to improve human medicine through translational, basic
science by establishing an independent research program focused on mechanisms of respiratory control, and
developing therapeutic strategies to treat pulmonary insufficiencies that occur during neuromuscular
impairments. The research and career development plans have been carefully designed to provide the
necessary skills for Dr. Streeter to establish a novel, independent line of research and include the following
objectives: 1) acquire core knowledge in respiratory neurobiology and cardiovascular control, 2) gain further
expertise in research methodology, techniques, and scientific writing, and 3) develop academic leadership
skills. ENVIRONMENT: Drs. Fuller and Davenport are exceptional mentors, with a track record of successful
mentees. Dr. Fuller has expertise in spinal cord injury (SCI) and neuroplasticity, and Dr. Davenport is an
authority on phrenic afferents and respiratory control. Both have NIH funding and productive laboratories, and
will provide the resources to assist the candidate in her research project. The sponsoring institution, the
University of Florida, is an ideal place to conduct the mentored studies due to outstanding faculty mentors, top-
notch facilities, and opportunities within the Center for Respiratory Research and Rehabilitation. RESEARCH:
The proposed research will determine the contribution of phrenic afferents to respiratory control in spinal intact
and injured rodents. Cervical SCI disrupts descending drive to the primary inspiratory muscle, the diaphragm,
and results in a profound breathing impairment. Diaphragm (phrenic) sensory afferent neurons are a novel
target due to their role in the regulation of respiratory activity. The fundamental goal of this proposal is to
determine the functional contribution of phrenic afferents to respiratory motor output following cervical SCI.
Three specific aims are proposed in rats with sub-acute (3-4 wks) cervical SCI: AIM 1: To test the hypothesis
that acute activation of phrenic afferents increases phrenic motor output; AIM 2: To test the hypothesis that
repeated activation of phrenic afferents induces phrenic motor plasticity associated with altered functional
connectivity in the spinal cord; AIM 3: To test the hypothesis that activation of phrenic afferents during the
clinically used strategy of diaphragm pacing, improves respiratory neuromuscular control. Since individuals
with cervical SCI are also at the highest risk for developing abhorrent driven cardiovascular responses (e.g.,
autonomic dysreflexia) and activation of phrenic afferents can be powerful regulator of heart rate and arterial
blood pressure, we will evaluate these variables during each aim. The added focus on cardiovascular
regulation provides an additional career development opportunity for Dr. Streeter, and we recruited an expert in
this area (Dr. Hayward) to serve on the mentoring team. We propose to use an established rodent model of
cervical SCI (C2 hemisection) and a multi-disciplinary approach including in vivo neurophysiology, electrical
stimulation, multi-electrode recordings, immunohistochemistry and chronic EMG recordings/stimulation.