Inactivity-induced phrenic motor facilitation requires PKCζ activity within phrenic motor neurons

Area of Science:

• Neuroscience
• Respiratory Physiology
• Molecular Biology

Background:

• Prolonged inhibition of respiratory neural activity induces lasting plasticity.
• Inactivity-induced phrenic motor facilitation (iPMF) and inspiratory intercostal motor facilitation (iIMF) are forms of this plasticity.
• Atypical protein kinase C (PKC) activity is crucial, but the specific isoform and location are unknown.

Purpose of the Study:

• To investigate the role of the atypical PKC zeta isoform (PKCζ) in phrenic and intercostal motor neurons.
• To determine if PKCζ in phrenic motor neurons is necessary for iPMF.
• To assess if PKCζ in intercostal motor neurons is necessary for iIMF.

Main Methods:

• RNA interference (siRNA) was used to target PKCζ in rat phrenic and intercostal motor neurons.
• Rats were subjected to neural apnea (respiratory inactivity) or a time control.
• Phrenic nerve activity and intercostal electromyographic (EMG) activity were measured.

Main Results:

• Knockdown of PKCζ in phrenic motor neurons abolished iPMF.
• PKCζ knockdown attenuated iIMF, indicating a partial role.
• PKCζ inhibition also blocked the enhanced phrenic response to hypercapnia after neural inactivity.

Conclusions:

• PKCζ within phrenic motor neurons is essential for long-lasting iPMF.
• PKCζ in intercostal motor neurons contributes to, but is not required for, transient iIMF.
• These findings elucidate key molecular mechanisms underlying respiratory motor plasticity.