Interfering with the Actin Network and Its Effect on Long-Term Potentiation and Synaptic Tagging in Hippocampal CA1 Neurons in SlicesIn Vitro

Abstract

Long-term potentiation (LTP) is a cellular correlate for memory formation, which requires the dynamic changes of the actin cytoskeleton. As shown by others, the polymerization of the actin network is important for early stages of LTP. Here, we investigated the role of actin dynamics in synaptic tagging and particularly in the induction of protein synthesis-dependent late-LTP in the CA1 region in hippocampal slices in vitro. We found that the inhibition of actin polymerization affects protein synthesis-independent early-LTP, prevents late-LTP, and interferes with synaptic tagging in apical dendrites of hippocampal CA1. The transformation of early-LTP into late-LTP was blocked by the application of the structurally different actin polymerization inhibitors latrunculin A or cytochalasin D. We suggest that the actin network is required for early "housekeeping" processes to induce and maintain early-LTP. Furthermore, inhibition of actin dynamics negatively interacts with the setting of the synaptic tagging complex. We propose actin as a further tag-specific molecule in apical CA1 dendrites where it is directly involved in the tagging/capturing machinery. Consequently, inhibition of the actin network prevents the interaction of tagging complexes with plasticity-related proteins. This results in the prevention of late-LTP by inhibition of the actin network during LTP induction.