Abstract

Alzheimer's disease (AD) is characterized by the accumulation of soluble amyloid-beta oligomers (A beta Os) in the brain, which disrupt synaptic function and promote cognitive decline. Here, we investigated the effects of A beta Os on excitatory and inhibitory synaptic transmission and plasticity by performing stereotaxic injections of A beta Os directly into the hippocampal CA1 region, followed by hippocampal slice isolation for electrophysiological measurements. A beta Os injections altered basal excitatory synaptic transmission, reducing field excitatory postsynaptic potentials (fEPSPs) and impairing excitatory long-term potentiation (LTP). Additionally, A beta Os injections significantly increased basal inhibitory synaptic transmission, as evidenced by the increased amplitude of field inhibitory postsynaptic potentials (fIPSPs), but impaired the induction and maintenance of inhibitory long-term potentiation (iLTP). Accordingly, we propose that A beta Os injections induce the saturation of the GABAergic system and thus disrupt the hippocampal excitatory-inhibitory balance. These findings highlight the dual impact of A beta Os on both excitatory and inhibitory synapses, generating synaptic dysregulation and possibly worsening cognitive decline in AD. Understanding these mechanisms could provide new insights for developing therapies to restore synaptic balance and hippocampal function in AD.