Adrenergic ß receptor activation in the basolateral amygdala, which is intracellular Zn2+-dependent, rescues amyloid ß1-42-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 ß receptor activation in the BLA rescues amyloid ß1-42 (Aß1-42)-induced attenuation of long-term potentiation (LTP) at perforant pathway-dentate granule cell (DGC) synapses. When 500 µM isoproterenol (2 µl), an adrenergic ß 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 ß receptor activation in the BLA. Aß1-42-induced attenuation of LTP, which was induced by Aß1-42 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, Aß1-42-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 ß receptor activation in the BLA, which is linked with intracellular Zn2+ signaling, rescues Aß1-42-induced attenuation of dentate gyrus LTP. It is likely that adrenergic ß receptor activation in the BLA is a strategy for rescuing Aß1-42-induced cognitive decline that is associated with hippocampal synaptic plasticity.

Blockade of intracellular Zn2+ signaling in the basolateral amygdala affects object recognition memory via attenuation of dentate gyrus LTP.

Hippocampus-dependent memory is modulated by the amygdala. However, it is unknown whether intracellular Zn2+ signaling in the amygdala is involved in hippocampus-dependent memory. On the basis of the evidence that intracellular Zn2+ signaling in dentate granule cells (DGC) is necessary for object recognition memory via LTP at medial perforant pathway (PP)-DGC synapses, the present study examined whether intracellular Zn2+ signaling in the amygdala influences object recognition memory via modulation of LTP at medial PP-DGC synapses. When ZnAF-2DA (100 µM, 2 µl) was injected into the basolateral amygdala (BLA), intracellular ZnAF-2 locally chelated intracellular Zn2+ in the amygdala. Recognition memory was affected when training of object recognition test was performed 20 min after ZnAF-2DA injection into the BLA. Twenty minutes after injection of ZnAF-2DA into the BLA, LTP induction at medial PP-DGC synapses was attenuated, while LTP induction at PP-BLA synapses was potentiated and LTP induction at BLA-DGC synapses was attenuated. These results suggest that intracellular Zn2+ signaling in the BLA is involved in BLA-associated LTP and modulates LTP at medial PP-DGC synapses, followed by modulation of object recognition memory.