Cyclic AMP-dependent attenuation of oscillatory-activity-induced intercortical strengthening of horizontal pathways between insular and parietal cortices.

Cyclic AMP (cAMP) is a key intracellular second messenger, and the intracellular cAMP signaling pathway acts to modulate various brain functions. We have previously reported that low-frequency insular cortex stimulation in rat brain slices switches on a voltage oscillator in the parietal cortex that delivers signals horizontally back and forth under caffeine application. The oscillatory activities are N-methyl-D-aspartate (NMDA) receptor-dependent, and the role of oscillation is to strengthen functional intercortical connections. The present study investigated actions of the cAMP signaling pathway on caffeine-induced strengthening of intercortical connections and tried to confirm the role of oscillation on intercortical strengthening by focusing on the cAMP pathway. After induction of parietal oscillation by insular cortex stimulation in caffeine-containing medium, application of membrane-permeable cAMP analog, bromo-cAMP, diminished oscillatory signal delivery from the parietal cortex, but initial insulo-parietal signal propagation remained strong. When oscillatory activities were reduced with co-application of caffeine and bromo-cAMP from the beginning, initial insulo-parietal propagation was established, but amplitudes of propagating wavelets and propagating velocity were reduced. Thus, cAMP-dependent diminution of caffeine-induced NMDA-receptor-dependent oscillatory signal delivery causes attenuation of intercortical strengthening of horizontal pathways between insular and parietal cortices. This finding suggests that the intracellular cAMP signaling pathway has the ability to regulate extracellular communications at the network level, and also that full expression of strengthened intercortical signal communication requires sufficient NMDA-receptor-dependent oscillatory neural activities.