Aβ induces acute depression of excitatory glutamatergic synaptic transmission through distinct phosphatase-dependent mechanisms in rat CA1 pyramidal neurons

• 1 μM synthetic Aβ oligomers can cause acute depression of synaptic transmission.
• Both presynaptic and postsynaptic dysfunction exists in this acute depression.
• PP1/2A is involved in Aβ-induced postsynaptic but not presynaptic dysfunction.
• PP2B is implicated in both presynaptic and postsynaptic dysfunction.

Beta-amyloid peptide (Aβ) has a causal role in the pathophysiology of Alzheimer’s disease (AD). Recent studies indicate that Aβ can disrupt excitatory glutamatergic synaptic function at synaptic level. However, the underlying mechanisms remain obscure. In this study, we recorded evoked and spontaneous EPSCs in hippocampal CA1 pyramidal neurons via whole-cell voltage-clamping methods and found that 1 μM Aβ can induce acute depression of basal glutamatergic synaptic transmission through both presynaptic and postsynaptic dysfunction. Moreover, we also found that Aβ-induced both presynaptic and postsynaptic dysfunction can be reversed by the inhibitor of protein phosphatase 2B (PP2B), FK506, whereas only postsynaptic disruption can be ameliorated by the inhibitor of PP1/PP2A, Okadaic acid (OA). These results indicate that PP1/PP2A and PP2B have overlapping but not identical functions in Aβ-induced acute depression of excitatory glutamatergic synaptic transmission of hippocampal CA1 pyramidal neurons.