PMID- 11880483 OWN - NLM STAT- MEDLINE DCOM- 20020322 LR - 20220309 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 22 IP - 5 DP - 2002 Mar 1 TI - Brain-derived neurotrophic factor induces long-term potentiation in intact adult hippocampus: requirement for ERK activation coupled to CREB and upregulation of Arc synthesis. PG - 1532-40 AB - Brain-derived neurotrophic factor (BDNF) is implicated in long-term synaptic plasticity in the adult hippocampus, but the cellular mechanisms are little understood. Here we used intrahippocampal microinfusion of BDNF to trigger long-term potentiation (BDNF-LTP) at medial perforant path--granule cell synapses in vivo. BDNF infusion led to rapid phosphorylation of the mitogen-activated protein (MAP) kinases ERK (extracellular signal-regulated protein kinase) and p38 but not JNK (c-Jun N-terminal protein kinase). These effects were restricted to the infused dentate gyrus; no changes were observed in microdissected CA3 and CA1 regions. Local infusion of MEK (MAP kinase kinase) inhibitors (PD98059 and U0126) during BDNF delivery abolished BDNF-LTP and the associated ERK activation. Application of MEK inhibitor during established BDNF-LTP had no effect. Activation of MEK-ERK is therefore required for the induction, but not the maintenance, of BDNF-LTP. BDNF-LTP was further coupled to ERK-dependent phosphorylation of the transcription factor cAMP response element-binding protein. Finally, we investigated the expression of two immediate early genes, activity-regulated cytoskeleton-associated protein (Arc) and Zif268, both of which are required for generation of late, mRNA synthesis-dependent LTP. BDNF infusion resulted in selective upregulation of mRNA and protein for Arc. In situ hybridization showed that Arc transcripts are rapidly and extensively delivered to granule cell dendrites. U0126 blocked Arc upregulation in parallel with BDNF-LTP. The results support a model in which BDNF triggers long-lasting synaptic strengthening through MEK-ERK and selective induction of the dendritic mRNA species Arc. FAU - Ying, Shui-Wang AU - Ying SW AD - Department of Physiology and Locus on Neuroscience, University of Bergen, N-5009 Bergen, Norway. FAU - Futter, Marie AU - Futter M FAU - Rosenblum, Kobi AU - Rosenblum K FAU - Webber, Mark J AU - Webber MJ FAU - Hunt, Stephen P AU - Hunt SP FAU - Bliss, Timothy V P AU - Bliss TV FAU - Bramham, Clive R AU - Bramham CR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Cytoskeletal Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (Nerve Tissue Proteins) RN - 0 (RNA, Messenger) RN - 0 (activity regulated cytoskeletal-associated protein) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cyclic AMP Response Element-Binding Protein/*metabolism MH - Cytoskeletal Proteins/genetics/*metabolism MH - Enzyme Activation/drug effects/physiology MH - Enzyme Inhibitors/pharmacology MH - Hippocampus/*drug effects/physiology MH - In Situ Hybridization MH - JNK Mitogen-Activated Protein Kinases MH - Long-Term Potentiation/*drug effects/physiology MH - Male MH - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism MH - Nerve Tissue Proteins/genetics/*metabolism MH - Phosphorylation/drug effects MH - Protein Serine-Threonine Kinases/antagonists & inhibitors MH - RNA, Messenger/metabolism MH - Rats MH - Signal Transduction/drug effects/physiology MH - Up-Regulation/drug effects/physiology MH - p38 Mitogen-Activated Protein Kinases PMC - PMC6758896 EDAT- 2002/03/07 10:00 MHDA- 2002/03/23 10:01 PMCR- 2002/09/01 CRDT- 2002/03/07 10:00 PHST- 2002/03/07 10:00 [pubmed] PHST- 2002/03/23 10:01 [medline] PHST- 2002/03/07 10:00 [entrez] PHST- 2002/09/01 00:00 [pmc-release] AID - 22/5/1532 [pii] AID - 6102 [pii] AID - 10.1523/JNEUROSCI.22-05-01532.2002 [doi] PST - ppublish SO - J Neurosci. 2002 Mar 1;22(5):1532-40. doi: 10.1523/JNEUROSCI.22-05-01532.2002.