Differential BDNF signaling in dentate gyrus and perirhinal cortex during consolidation of recognition memory in the rat.

Consolidation of long-term memory is dependent on synthesis of new proteins in the hippocampus and associated cortical regions. The neurotrophin brain-derived neurotrophic factor (BDNF) is tightly regulated by activity-dependent cellular processes and is strongly linked with mechanisms underlying learning and memory. BDNF activation of tyrosine receptor kinase (TrkB) stimulates intracellular signaling cascades implicated in plasticity, including the extracellular-signal related kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositide-3-kinase (PI3K)/Akt pathway. Here, we investigate the role of BDNF, ERK/MAPK, and PI3K/AKT signaling cascade in recognition memory in the rat. We report that recognition memory was associated with increased release of BDNF in the dentate gyrus and perirhinal cortex. This was associated with significant increases in p44ERK activation and c-fos expression in the dentate gyrus and PI3K activation and c-fos expression in the perirhinal cortex. Furthermore, both recognition memory and the associated cell signaling events in dentate gyrus and perirhinal cortex were blocked by intraperitoneal injection of the Trk receptor inhibitor tyrphostin AG879. These data are consistent with the hypothesis that BDNF-stimulated intracellular signaling plays a role in consolidation of recognition memory in the rat.