Involvement of isoproterenol-induced intracellular Zn2+ dynamics in the basolateral amygdala in conditioned fear memory.

Beta-adrenergic receptors in the basolateral amygdala play an essential role in fear memory, while the physiological role of intracellular Zn2+ remains to be clarified. Intracellular Zn2+ level was decreased 5 min after local injection of 500 μM isoproterenol (2 μl), a nonselective beta-adrenergic receptor agonist into the basolateral amygdala, suggesting that intracellular Zn2+ dynamic is linked with beta-adrenergic receptor signaling in the basolateral amygdala. When isoproterenol was injected into the basolateral amygdala 20 min prior to long-term potentiation (LTP) induction, LTP at perforant pathway-basolateral amygdala was enhanced and conditioned fear memory was also augmented, suggesting that isoproterenol leads to utilization of Zn2+ to consolidate fear memory followed by lowering intracellular Zn2+. We postulated that synaptic Zn2+ dynamics under conditioned fear experience regulates conditioned fear memory in cooperation with beta-adrenergic receptor signaling. When either intracellular Zn2+ chelator (ZnAF-2DA) or extracellular Zn2+ chelator (CaEDTA) was locally injected into the basolateral amygdala in the same manner, LTP was also enhanced. The local injection of ZnAF-2DA augmented fear memory. It is likely that the decrease in availability of intracellular Zn2+ by Zn2+ chelators under fear experience affects the function of Zn2+-required proteins followed by augmentation of fear memory and its related LTP. The present study suggests that beta-adrenergic receptor signaling is linked with intracellular Zn2+ signaling in the basolateral amygdala to consolidate conditioned fear memory. Because intracellular Zn2+ signaling is required for fear memory, the decrease in availability of intracellular Zn2+ may augment fear memory and its related LTP under non-physiological condition.