Adrenergic β receptor activation in the basolateral amygdala, which is intracellular Zn2+-dependent, rescues amyloid β1-42-induced attenuation of dentate gyrus LTP.
On the basis of the evidence that the basolateral amygdala (BLA) modulates hippocampal memory processes via synaptic plasticity, here we report that adrenergic β receptor activation in the BLA rescues amyloid β1-42 (Aβ1-42)-induced attenuation of long-term potentiation (LTP) at perforant pathway-dentate granule cell (DGC) synapses. When 500 μM isoproterenol (2 μl), an adrenergic β receptor agonist, was injected into the BLA 20 min before LTP induction, LTP was enhanced. Isoproterenol-mediated enhancement of LTP was blocked by co-injection with 100 μM ZnAF-2DA, an intracellular Zn2+ chelator, suggesting that intracellular Zn2+ is required for the intracellular signaling cascade after adrenergic β receptor activation in the BLA. Aβ1-42-induced attenuation of LTP, which was induced by Aβ1-42 injection into the dentate gyrus 60 min before LTP induction, was rescued by isoproterenol injection into the BLA 20 min before LTP induction, but not by 500 μM phenylephrine (2 μl), an adrenergic α1 receptor agonist, injection into the BLA, which did not enhance LTP unlike the case of isoproterenol injection. Interestingly, Aβ1-42-induced attenuation of LTP was also rescued by 100 μM isoproterenol injection into the BLA 20 min before LTP induction, which did not enhance LTP. The present study demonstrates that adrenergic β receptor activation in the BLA, which is linked with intracellular Zn2+ signaling, rescues Aβ1-42-induced attenuation of dentate gyrus LTP. It is likely that adrenergic β receptor activation in the BLA is a strategy for rescuing Aβ1-42-induced cognitive decline that is associated with hippocampal synaptic plasticity.
['Tamano|Haruna|H|', 'Kubota|Mitsuyasu|M|', 'Fujise|Yuki|Y|', 'Shimaya|Ryota|R|', 'Itoh|Ryusei|R|', 'Suzuki|Miki|M|', 'Adlard|Paul A|PA|', 'Bush|Ashley I|AI|', 'Takeda|Atsushi|A|']
D016229:Amyloid beta-Peptides D000818:Animals D066272:Basolateral Nuclear Complex D002614:Chelating Agents D018891:Dentate Gyrus D006624:Hippocampus D017774:Long-Term Potentiation D008297:Male D008568:Memory D009474:Neurons D010446:Peptide Fragments D017208:Rats, Wistar D018342:Receptors, Adrenergic, beta-1 D013569:Synapses
Amygdala Dentate gyrus LTP Isoproterenol Amyloid β(1-42) Zinc