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

• Published in: Biometals Vol. 35; no. 5; pp. 1023 - 1031
• Main Authors: Itoh, Ryusei, Ishikawa, Yudai, Tamano, Haruna, Takeda, Atsushi
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.10.2022; Springer Nature B.V
• Subjects: Adrenergic receptors; Amygdala; Animal memory; Availability; Biochemistry; Biomedical and Life Sciences; Cell Biology; Chelating agents; Cooperativity; Fear; Fear conditioning; Injection; Intracellular; Intracellular signalling; Isoproterenol; Life Sciences; Long-term potentiation; Medicine/Public Health; Microbiology; Pharmacology/Toxicology; Physiology; Plant Physiology; Receptors (physiology); Signaling; Zinc; Basolateral amygdala; Fear memory; LTP; signaling; Zn; Isoproterenol
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1007/s10534-022-00420-6

Beta-adrenergic receptors in the basolateral amygdala play an essential role in fear memory, while the physiological role of intracellular Zn 2+ remains to be clarified. Intracellular Zn 2+ 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 Zn 2+ 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 Zn 2+ to consolidate fear memory followed by lowering intracellular Zn 2+ . We postulated that synaptic Zn 2+ dynamics under conditioned fear experience regulates conditioned fear memory in cooperation with beta-adrenergic receptor signaling. When either intracellular Zn 2+ chelator (ZnAF-2DA) or extracellular Zn 2+ 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 Zn 2+ by Zn 2+ chelators under fear experience affects the function of Zn 2+ -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 Zn 2+ signaling in the basolateral amygdala to consolidate conditioned fear memory. Because intracellular Zn 2+ signaling is required for fear memory, the decrease in availability of intracellular Zn 2+ may augment fear memory and its related LTP under non-physiological condition.