Intraventricular murine Aβ infusion elicits hippocampal inflammation and disrupts the consolidation, but not retrieval, of conditioned fear in C57BL6/J mice.

Although one of the defining characteristics of Alzheimer’s disease is the presence of amyloid-beta (Aβ) plaques, the early accumulation of soluble Aβ oligomers (AβOs) may disrupt synaptic function and trigger cognitive impairments long before the appearance of plaques. Furthermore, murine models aimed at understanding how AβOs alter formation and retrieval of associative memories are conducted using human Aβ species, which are more neurotoxic in the mouse brain than the native murine species. Unfortunately, there is currently a lack of attention in the literature as to what the murine version of the peptide (mAβ) does to synaptic function and how it impacts the consolidation and retrieval of associative memories. In the current study, adult mice were infused with mAβ 0, 2, 6, or 46 h after contextual-fear conditioning, and were tested 2–48 h later. Interestingly, only mAβ infusions within 2 h of training reduced freezing behavior at test, indicating that mAβ disrupted the consolidation, but not retrieval of fear memory. This consolidation deficit coincided with increased IL-1β and reduced synaptophysin mRNA levels, without disrupting other synaptic signaling-related genes here examined. Despite differences between murine and human Aβ, the deleterious functional outcomes of early-stage synaptic oligomer presence are similar. Thus, models utilizing or inducing the production of mAβ in non-transgenic animals are useful in exploring the role of dysregulated synaptic plasticity and resultant learning deficits induced by Aβ oligomers.