Long‐lasting substance‐P‐mediated modulation of NMDA‐induced rhythmic activity in the lamprey locomotor network involves separate RNA‐ and protein‐synthesis‐dependent stages

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Abstract
Bath application of the tachykinin neuropeptide substance P (1 μm) for 10 min causes long‐lasting (> 24 h) modulation of the frequency and regularity of NMDA‐evoked locomotor bursts in the lamprey. The change in burst frequency has an induction phase (< 2 h), which depends on the potentiation of NMDA responses and an increase in intracellular calcium levels, and a maintenance phase (> 2 h), that is blocked by translational protein synthesis inhibitors. Here, the maintenance phase has been examined further. Unlike translation inhibitors, the transcription inhibitors actinomycin D and 5,6‐dichlorobenzimidazole riboside (DRB) failed to reverse the change in burst frequency 2–3 h after substance P application, suggesting that the protein synthesized at this time does not require de novo RNA synthesis. Transcription inhibitors, however, reversed the change in burst frequency 15–24 h after substance P application, as did brefeldin A, which disrupts the Golgi complex and thus interferes with the post‐translational transport of proteins. The change in burst regularity was unaffected by transcription or translation inhibitors, but was partially reversed by protein kinase A inhibitors applied 2.5–8 h after substance P. The glycoprotein synthesis inhibitor 2‐deoxygalactose did not affect the changes in burst frequency or burst regularity. These results suggest that there are two phases to the maintenance of the change in burst frequency: an intermediate protein‐, but not RNA‐, synthesis‐dependent phase, and a final RNA‐synthesis‐dependent phase. The change in burst regularity is protein‐synthesis‐independent, but may depend on activation of protein kinase A for at least 8 h after substance P application.