Induction of β-adrenergic metaplasticity of LTP requires intact anchoring of PKA

Abstract

Beta-adrenergic receptors (β-ARs) prime hippocampal synapses to stabilize long-term potentiation (LTP). This “metaplasticity” can persist for 1–2 h after pharmacologic activation of β-ARs. It requires activation of PKA (cAMP-dependent protein kinase) during β-AR priming. A-kinase anchoring proteins (AKAPs) tether PKA to downstream signaling proteins. We hypothesized that induction of this metaplasticity requires intact functioning of AKAPs. Acute application of stearated ht31, a membrane-permeant inhibitor of AKAPs, either during β-AR activation 30 min prior to LTP induction or during LTP induction, attenuated the persistence of LTP. A control, inactive ht31 peptide did not affect β-AR-mediated metaplasticity. These findings implicate PKA anchoring in the induction of β-adrenergic metaplasticity of LTP.