Long-term potentiation (LTP) in the hippocampus is the most extensive form of long-lasting synaptic plasticity and is widely regarded as the cellular basis of memory formation. The canonical NMDA-receptor (NMDAR)-dependent form of LTP can be differentiated into protein kinase A (PKA)-dependent and -independent forms by the spacing between theta burst stimuli (TBS) induction. Key features of PKA-dependent LTP includes insertion of Ca2+ permeable AMPA receptors (CP-AMPARs) and initiation of de novo protein synthesis. However, the molecular mechanisms that elicit these processes remain unknown. Previous studies suggest PKA can regulate LIM-domain kinase (LIMK) 1, but this regulation has not been demonstrated in synaptic plasticity. Using a combination of electrophysiology, genetic mouse models, and pharmacology, I show that CP-AMPAR-dependent LTP requires PKA regardless of TBS spacing. Furthermore, I demonstrate that LIMK1 is required for PKA-dependent LTP. These findings provide insight into the molecular mechanisms underlying LTP and long-term memory formation.M.Sc.2020-03-21 00:00:0
