Plasticity in Diaphragm and Intercostal Motor Control in a Rat ALS Model

Ventilatory capacity is preserved in rat models of ALS until late in disease progression despite major respiratory motor neuron (MN) loss (~80% cervical and ~65% thoracic) and reduced phrenic activity (~50%). However, mechanisms preserving ventilatory capacity are not known. We hypothesized that external intercostal (IC) EMG activity is enhanced in late stage ALS rats to preserve ventilatory function. EMG activities of diaphragm (DIA), second (IC2) and fifth (IC5) IC muscles were recorded in anesthetized, spontaneously breathing rats during regulated normoxia (Nox: arterial PO 2 ~90mmHg), room air breathing, maximal chemoreceptor stimulation (MCS: 10% O 2 /7% CO 2 ), spontaneous sighs and tracheal occlusion. SOD1 G93A transgenic rats were tested at 20% weight loss and compared to age‐matched, wild‐type littermates. During Nox, room air breathing, DIA and IC2 root‐mean‐squared (RMS) EMG activities were comparable, whereas IC5 RMS EMG was significantly increased in mutant rats (p<0.01). EMG activities of all muscles were reduced during sighs and occlusion in mutant rats (p<0.05). Reserve capacity (Peak RMS EMG during sighs normalized to Nox) was reduced by 40%, 64% and 82% in DIA, IC2 and IC5, respectively. Sigh frequency increased >2‐fold in mutant rats during MCS. To summarize, in late stage ALS, caudal IC muscle activity is selectively enhanced to preserve ventilatory function, suggesting plasticity in the utilization of respiratory muscles. Conserved DIA EMG activity despite reduced phrenic MN numbers and activity suggests DIA neuromuscular junction plasticity and/or MN branching. Supported by NIH 69064, K99 HL119606 and DoD W81XWH‐13‐1‐0410.