PMID- 12196567 OWN - NLM STAT- MEDLINE DCOM- 20020913 LR - 20200225 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 22 IP - 17 DP - 2002 Sep 1 TI - Brain-derived neurotrophic factor triggers transcription-dependent, late phase long-term potentiation in vivo. PG - 7453-61 AB - Acute intrahippocampal infusion of brain-derived neurotrophic factor (BDNF) leads to long-term potentiation (BDNF-LTP) of synaptic transmission at medial perforant path-->granule cell synapses in the rat dentate gyrus. Endogenous BDNF is implicated in the maintenance of high-frequency stimulation-induced LTP (HFS-LTP). However, the relationship between exogenous BDNF-LTP and HFS-LTP is unclear. First, we found that BDNF-LTP, like HFS-LTP, is associated with enhancement in both synaptic strength and granule cell excitability (EPSP-spike coupling). Second, treatment with a competitive NMDA receptor (NMDAR) antagonist blocked HFS-LTP but had no effect on the development or magnitude of BDNF-LTP. Thus, NMDAR activation is not required for the induction or expression of BDNF-LTP. Formation of stable, late phase HFS-LTP requires mRNA synthesis and is coupled to upregulation of the immediate early gene activity-regulated cytoskeleton-associated protein (Arc). Local infusion of the transcription inhibitor actinomycin D (ACD) 1 hr before or immediately before BDNF infusion inhibited BDNF-LTP and upregulation of Arc protein expression. ACD applied 2 hr after BDNF infusion had no effect, defining a critical time window of transcription-dependent synaptic strengthening. Finally, the functional role of BDNF-LTP was assessed in occlusion experiments with HFS-LTP. HFS-LTP was induced, and BDNF was infused at time points corresponding to early phase (1 hr) or late phase (4 hr) HFS-LTP. BDNF applied during the early phase led to normal BDNF-LTP. In contrast, BDNF-LTP was completely occluded during the late phase. The results strongly support a role for BDNF in triggering transcription-dependent, late phase LTP in the intact adult brain. FAU - Messaoudi, Elhoucine AU - Messaoudi E AD - Department of Physiology and Locus on Neuroscience, University of Bergen, N-5009 Bergen, Norway. FAU - Ying, Shui-Wang AU - Ying SW FAU - Kanhema, Tambudzai AU - Kanhema T FAU - Croll, Susan D AU - Croll SD 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 (Cytoskeletal Proteins) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Immediate-Early Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nucleic Acid Synthesis Inhibitors) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (activity regulated cytoskeletal-associated protein) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacokinetics/*pharmacology MH - Cytoskeletal Proteins MH - Drug Administration Routes MH - Electric Stimulation/methods MH - Excitatory Amino Acid Antagonists/pharmacology MH - Excitatory Postsynaptic Potentials/drug effects/physiology MH - Hippocampus/*drug effects/physiology MH - Immediate-Early Proteins/metabolism MH - Long-Term Potentiation/*drug effects/physiology MH - *Nerve Tissue Proteins MH - Neuronal Plasticity/drug effects/physiology MH - Nucleic Acid Synthesis Inhibitors/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors MH - Synaptic Transmission/drug effects/physiology MH - Tissue Distribution MH - Transcription, Genetic/*drug effects/physiology MH - Up-Regulation/drug effects PMC - PMC6757978 EDAT- 2002/08/28 10:00 MHDA- 2002/09/14 10:01 PMCR- 2003/03/01 CRDT- 2002/08/28 10:00 PHST- 2002/08/28 10:00 [pubmed] PHST- 2002/09/14 10:01 [medline] PHST- 2002/08/28 10:00 [entrez] PHST- 2003/03/01 00:00 [pmc-release] AID - 22/17/7453 [pii] AID - 6728 [pii] AID - 10.1523/JNEUROSCI.22-17-07453.2002 [doi] PST - ppublish SO - J Neurosci. 2002 Sep 1;22(17):7453-61. doi: 10.1523/JNEUROSCI.22-17-07453.2002.