Phrenic Long-Term Facilitation Requires PKC{theta} Activity within Phrenic Motor Neurons

Acute intermittent hypoxia (AIH) induces a form of spinal motor plasticity known as phrenic long-term facilitation (pLTF); pLTF is a prolonged increase in phrenic motor output after AIH has ended. In anesthetized rats, we demonstrate that pLTF requires activity of the novel PKC isoform, PKC, and that the relevant PKC is within phrenic motor neurons. Whereas spinal PKC inhibitors block pLTF, inhibitors targeting other PKC isoforms do not. PKC is highly expressed in phrenic motor neurons, and PKC knockdown with intrapleural siRNAs abolishes pLTF. Intrapleural siRNAs targeting PKC, an atypical PKC isoform expressed in phrenic motor neurons that underlies a distinct form of phrenic motor plasticity, does not affect pLTF. Thus, PKC plays a critical role in spinal AIH-induced respiratory motor plasticity, and the relevant PKC is localized within phrenic motor neurons. Intrapleural siRNA delivery has considerable potential as a therapeutic tool to selectively manipulate plasticity in vital respiratory motor neurons.