CONTROL OF DIAPHRAGM ACTIVITY AFTER SCI IN THE ABSENCE OF SUPRASPINAL INPUT: THE CONTRIBUTION OF INTERNEURONS

CONTROL OF DIAPHRAGM ACTIVITY AFTER SCI IN THE ABSENCE OF SUPRASPINAL INPUT: THE CONTRIBUTION OF INTERNEURONS

Jared Cregg at Asilomar California 2015 ISNR Conference during posters

Jared Cregg at Asilomar California 2015 ISNR Conference during poster presentations


Respiratory drive is relayed to phrenic motor neurons via bulbospinal projections. Spinal cord injury at or above cervical level 4 disrupts these descending projections and causes permanent loss of diaphragm function. In this study we examined whether cervical spinal cord circuitry— circuitry that retains local connectivity after high cervical spinal cord injury—can be mobilized to control the diaphragm in the absence of descending input from bulbospinal premotor nuclei. Using an in situ model of cervical spinal cord injury we demonstrate that in the absence of supraspinal input, tonic inhibitory synaptic transmission suppresses phrenic motor output. Pharmacological blockade of GABAergic/glycinergic transmission relieves inhibitory synaptic input to phrenic motor neurons, and furthermore, uncovers an excitatory propriospinal circuit capable of driving synchronous right/left phrenic motor output. Under conditions of disinhibition, we find that we can precisely control phrenic motor output by optogenetic stimulation of excitatory interneurons at defined frequencies. These results identify spinal cord circuitry that can coordinate right/left phrenic motor output in the absence of descending command from bulbospinal premotor nuclei. We further show that this circuit can be mobilized to promote hemidiaphragm function after lateral C2 hemisection in vivo. Thus, taken together, we demonstrate that pre-phrenic spinal cord interneurons can be exploited to allow function of an otherwise paralyzed muscle required for sustaining life.

Cregg JM1, Landmesser LT1, Silver J1 1Department of Neurosciences, Case Western Reserve University, Cleveland OH 44106

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