Protein kinase A activators produce a short-term, but not long-term, increase in respiratory-drive transmission at the hypoglossal motor nucleus in vivo

Abstract

Synaptic plasticity is an intrinsic and conserved feature of neuronal activity that has been most extensively studied in the context of learning and memory in Aplysia and the mammalian hippocampus. However, the intracellular mechanisms underlying plasticity at motor nuclei, influencing motor behaviour, are less well studied. In vitro experiments in neonatal rodents indicate that protein kinase A (PKA) modulates respiratory-drive transmission at the hypoglossal motor nucleus (HMN), which innervates the genioglossus muscle of the tongue. We hypothesised that PKA activators at the HMN would increase genioglossus activity in vivo, whereas a PKA inhibitor would suppress activity indicative of constitutive PKA activation. Since PKA activators are importantly involved in models of long-term augmentation of neuronal activity following massed stimulation [16], we also hypothesised that application of PKA activators to the HMN would produce long-term facilitation of genioglossus activity. Experiments were performed in 25 isoflurane-anaesthetised, tracheotomised, spontaneously breathing adult rats. Microdialysis perfusion of 8-Br-cAMP (direct PKA activator) into the HMN increased genioglossus activity compared to baseline levels with artificial cerebrospinal fluid ( P < 0.001). Application of forskolin (indirect PKA activator) had a similar effect ( P < 0.002). Genioglossus activity progressively decreased back to baseline during a 90-min washout with artificial cerebrospinal fluid, demonstrating a lack of long-term facilitation of genioglossus activity. Similar to massed application of 8-Br-cAMP to the HMN, intermittent application produced a short-term ( P < 0.001), but not long-term, increase in genioglossus activity in vivo. Application of Rp-8-Cl-cAMPS (PKA inhibitor) did not decrease genioglossus activity, indicating a lack of constitutive PKA activation.