PMID- 23674394
OWN - NLM
STAT- MEDLINE
DCOM- 20141223
LR  - 20140408
IS  - 1098-1063 (Electronic)
IS  - 1050-9631 (Linking)
VI  - 23
IP  - 10
DP  - 2013 Oct
TI  - Blockade of BDNF signaling turns chemically-induced long-term potentiation into 
      long-term depression.
PG  - 879-89
LID - 10.1002/hipo.22144 [doi]
AB  - Long-term potentiation (LTP) is accompanied by increased spine density and 
      dimensions triggered by signaling cascades involving activation of the 
      neurotrophin brain-derived neurotrophic factor (BDNF) and cytoskeleton 
      remodeling. Chemically-induced long-term potentiation (c-LTP) is a widely used 
      cellular model of plasticity, whose effects on spines have been poorly 
      investigated. We induced c-LTP by bath-application of the N-methyl-d-aspartate 
      receptor (NMDAR) coagonist glycine or by the K(+) channel blocker 
      tetraethylammonium (TEA) chloride in cultured hippocampal neurons and compared 
      the changes in dendritic spines induced by the two models of c-LTP and determined 
      if they depend on BDNF/TrkB signaling. We found that both TEA and glycine induced 
      a significant increase in stubby spine density in primary and secondary apical 
      dendrites, whereas a specific increase in mushroom spine density was observed 
      upon TEA application only in primary dendrites. Both TEA and glycine increased 
      BDNF levels and the blockade of tropomyosin-receptor-kinase receptors (TrkRs) by 
      the nonselective tyrosine kinase inhibitor K-252a or the selective allosteric 
      TrkB receptor (TrkBR) inhibitor ANA-12, abolished the c-LTP-induced increase in 
      spine density. Surprisingly, a blockade of TrkBRs did not change basal 
      spontaneous glutamatergic transmission but completely changed the synaptic 
      plasticity induced by c-LTP, provoking a shift from a long-term increase to a 
      long-term depression (LTD) in miniature excitatory postsynaptic current (mEPSC) 
      frequency. In conclusion, these results suggest that BDNF/TrkB signaling is 
      necessary for c-LTP-induced plasticity in hippocampal neurons and its blockade 
      leads to a switch of c-LTP into chemical-LTD (c-LTD).
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Montalbano, A
AU  - Montalbano A
AD  - Department of Life Sciences and B.R.A.I.N., Centre for Neuroscience, University 
      of Trieste, Trieste, Italy.
FAU - Baj, G
AU  - Baj G
FAU - Papadia, D
AU  - Papadia D
FAU - Tongiorgi, E
AU  - Tongiorgi E
FAU - Sciancalepore, M
AU  - Sciancalepore M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130626
PL  - United States
TA  - Hippocampus
JT  - Hippocampus
JID - 9108167
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glycine Agents)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 66-40-0 (Tetraethylammonium)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/*metabolism
MH  - Cells, Cultured
MH  - Dendritic Spines/drug effects/*physiology
MH  - Excitatory Postsynaptic Potentials/drug effects
MH  - Glycine/pharmacology
MH  - Glycine Agents/pharmacology
MH  - Hippocampus/cytology/*metabolism
MH  - Long-Term Potentiation/drug effects/*physiology
MH  - Long-Term Synaptic Depression/drug effects/*physiology
MH  - Patch-Clamp Techniques
MH  - Potassium Channel Blockers/pharmacology
MH  - Rats, Wistar
MH  - Receptor, trkB/antagonists & inhibitors/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/agonists
MH  - Signal Transduction/drug effects/*physiology
MH  - Tetraethylammonium/pharmacology
OTO - NOTNLM
OT  - TEA; glycine
OT  - chemical LTD
OT  - chemical LTP
OT  - spine remodeling
EDAT- 2013/05/16 06:00
MHDA- 2014/12/24 06:00
CRDT- 2013/05/16 06:00
PHST- 2013/05/01 00:00 [accepted]
PHST- 2013/05/16 06:00 [entrez]
PHST- 2013/05/16 06:00 [pubmed]
PHST- 2014/12/24 06:00 [medline]
AID - 10.1002/hipo.22144 [doi]
PST - ppublish
SO  - Hippocampus. 2013 Oct;23(10):879-89. doi: 10.1002/hipo.22144. Epub 2013 Jun 26.