PMID- 10492006
OWN - NLM
STAT- MEDLINE
DCOM- 19991019
LR  - 20181113
IS  - 1072-0502 (Print)
IS  - 1072-0502 (Linking)
VI  - 6
IP  - 3
DP  - 1999 May-Jun
TI  - Signaling mechanisms mediating BDNF modulation of synaptic plasticity in the 
      hippocampus.
PG  - 243-56
AB  - Although recent studies indicate that brain-derived neurotrophic factor (BDNF) 
      plays an important role in hippocampal synaptic plasticity, the underlying 
      signaling mechanisms remain largely unknown. Here, we have characterized the 
      signaling events that mediate the BDNF modulation of high-frequency synaptic 
      transmission. Mitogen-associated protein kinase (MAPK), phosphotidylinositol-3 
      kinase (PI3K), and phospholipase C-gamma (PLC-gamma) are the three signaling 
      pathways known to mediate neurotrophin signaling in other systems. In neonatal 
      hippocampal slices, application of BDNF rapidly activated MAPK and PI3K but not 
      PLC-gamma. BDNF greatly attenuated synaptic fatigue at CA1 synapses induced by a 
      train of high-frequency, tetanic stimulation (HFS). Inhibition of the MAPK and 
      PI3K, but not PLC-gamma, prevented the BDNF modulation of high-frequency synaptic 
      transmission. Neurotrophin-3 (NT-3), a close relative of BDNF, did not activate 
      MAPK or PI3K and had no effect on synaptic fatigue in the neonatal hippocampus. 
      Neither forskolin, which activated MAPK but not PI3 kinase, nor ciliary 
      neurotrophic factor (CNTF), which activated PI3K but not MAPK, affected 
      HFS-induced synaptic fatigue. Treatment of the slices with forskolin together 
      with CNTF still had no effect on synaptic fatigue. Thus, although the activation 
      of MAPK and PI3K is required, the two together are not sufficient to mediate the 
      BDNF effect. Inhibition of new protein synthesis by anisomycin or cycloheximide 
      did not prevent the BDNF effect. These data suggest that BDNF modulation of 
      high-frequency transmission is independent of protein synthesis but requires MAPK 
      and PI3K and yet another signaling pathway to act together in the hippocampus.
FAU - Gottschalk, W A
AU  - Gottschalk WA
AD  - Unit on Synapse Development and Plasticity National Institute of Child Health and 
      Development, National Institutes of Health, Bethesda, Maryland 20892-4480, USA.
FAU - Jiang, H
AU  - Jiang H
FAU - Tartaglia, N
AU  - Tartaglia N
FAU - Feng, L
AU  - Feng L
FAU - Figurov, A
AU  - Figurov A
FAU - Lu, B
AU  - Lu B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Learn Mem
JT  - Learning & memory (Cold Spring Harbor, N.Y.)
JID - 9435678
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Isoenzymes)
RN  - 0 (Nerve Tissue Proteins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Electrophysiology
MH  - Hippocampus/*physiology
MH  - Isoenzymes/metabolism
MH  - Nerve Tissue Proteins/biosynthesis
MH  - Neuronal Plasticity/*physiology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phospholipase C gamma
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*physiology
MH  - Synapses/physiology
MH  - Type C Phospholipases/metabolism
PMC - PMC311299
EDAT- 1999/09/24 00:00
MHDA- 1999/09/24 00:01
PMCR- 2000/05/01
CRDT- 1999/09/24 00:00
PHST- 1999/09/24 00:00 [pubmed]
PHST- 1999/09/24 00:01 [medline]
PHST- 1999/09/24 00:00 [entrez]
PHST- 2000/05/01 00:00 [pmc-release]
PST - ppublish
SO  - Learn Mem. 1999 May-Jun;6(3):243-56.