Isoproterenol injected into the basolateral amygdala rescues amyloid β1-42-induced conditioned fear memory deficit via reducing intracellular Zn2+ toxicity

Abstract

On the basis of amyloid β (Aβ) peptides as triggers in atrophy of structures in the limbic system, here we postulated that Aβ1-42-induced intracellular Zn2+ toxicity in the basolateral amygdala contributes to conditioned fear memory. Aβ1-42 increased intracellular Zn2+ level in the amygdala after local injection of Aβ1-42 into the basolateral amygdala, resulting in conditioned fear memory deficit via attenuated LTP at perforant pathway-basolateral amygdala synapses. Co-injection of isoproterenol, a beta-adrenergic receptor agonist, reduced Aβ1-42-mediated increase in intracellular Zn2+, resulting in rescue of the memory deficit and attenuated LTP. The present study suggests that beta-adrenergic activity induced by isoproterenol in the basolateral amygdala rescues the impairment of conditioned fear memory by Aβ1-42. The rescuing effect may be linked with reducing Aβ1-42-induced intracellular Zn2+ toxicity. Furthermore, Aβ1-42 injection into the basolateral amygdala also attenuated LTP at perforant pathway-dentate granule cell synapses, while co-injection of isoproterenol rescued it, suggesting that Aβ1-42 toxicity in the basolateral amygdala also affects hippocampus-dependent memory. It is likely that beta-adrenergic receptor activation in the basolateral amygdala rescues the limbic system exposed to Aβ1-42 toxicity.