Synaptic Correlates of Anterograde Amnesia and Intact Retrograde Memory in a Mouse Model of Alzheimer’s Disease

Abstract

Background: Clinical evidence indicates that patients affected by Alzheimer's Disease (AD) fail to form new memories although their memories for old events are intact. This amnesic pattern depends on the selective vulnerability to AD-neurodegeneration of the hippocampus, the brain region that sustains the formation of new memories, while cortical regions that store remote memories are spared. Objective: To identify the cellular mechanisms underlying impaired recent memories and intact remote memories in a mouse model of AD. Method: Glutamatergic synaptic currents were recorded by patch-clamp in acute hippocampal and anterior Cingulate Cortical (aCC) slices of AD-like Tg2576 mice and Wild-type (Wt) littermates subjected to the Contextual Fear Conditioning (CFC) task or in naïve conditions. Results: Glutamatergic synaptic currents were recorded by patch-clamp in acute hippocampal and anterior Cingulate Cortical (aCC) slices of AD-like Tg2576 mice and Wild-type (Wt) littermates subjected to the Contextual Fear Conditioning (CFC) task or in naïve conditions. Conclusion: Our data suggest that in the early AD stages synaptic plasticity of CA1 synapses, crucial to form new memories, is lost, while plasticity of aCC synapses is intact and contributes to the persistence of long-term memories.