LTP mechanisms in the dentate gyrus in vivo: BDNF signaling, translation control, and gene function

This book illustrates some of the various molecular mechanisms underlying synaptic plasticity in a subfield of the rat hippocampus called dentate gyrus (DG). Long-term potentiation (LTP) is a well- known model for studying strengthening of synaptic plasticity. In this study, LTP was induced in the DG by intrahippocampal infusion of brain-derived neurotrophic factor (BDNF-LTP). Alternatively, LTP was induced at medial perforant path-granule cell synapses by high frequency stimulation (HFS-LTP). The aim of the study was investigation of transcriptional and translational changes of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) as well as changes in activation of the translation factors eIF4E (eukaryotic initiation factor 4E) and eEF2 (eukaryotic elongation factor-2) during LTP. We have demonstrated rapid activation of both translation factors and upregulation of Arc protein during BDNF-LTP. Additionally, an approach based on intrahippocampal infusion of Arc antisense oligodeoxynucleotides showed the importance of sustained Arc translation for the maintenance of both BDNF-LTP and HFS-LTP during a restricted time window.