Figure 7.

Schematic of postulated three-stage compensatory respiratory plasticity in end-stage SOD1^G93A rats; the figure is based on current and previous findings (Nichols et al., 2013a; Nichols et al., 2014; Nichols and Mitchell, 2016; Nichols et al., 2015). Phrenic motor neuron death is compensated by two distinct mechanisms: 1) spinal synaptic plasticity, amplifying translation of descending respiratory drive into the activity of the spared phrenic motor neurons; and 2) amplification of phrenic-diaphragm electrical transmission, preserving diaphragm electrical activity via unknown mechanisms that may include motor neuron sprouting and/or other mechanisms of enhanced neuromuscular junction transmission. Because of diaphragm dysfunction (reflected in a reduced Pdi), the third step is to increase the relative contributions of accessory inspiratory muscles, despite (lesser) intercostal motor neuron death. In concert, these forms of plasticity preserve breathing ability.