synaptic plasticity of respiratory motor output
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.
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.
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.
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.