PMID- 24335212
OWN - NLM
STAT- MEDLINE
DCOM- 20141030
LR  - 20220408
IS  - 1522-1598 (Electronic)
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 111
IP  - 5
DP  - 2014 Mar
TI  - BDNF-endocannabinoid interactions at neocortical inhibitory synapses require 
      phospholipase C signaling.
PG  - 1008-15
LID - 10.1152/jn.00554.2013 [doi]
AB  - Endogenous cannabinoids (endocannabinoids) and neurotrophins, particularly 
      brain-derived neurotrophic factor (BDNF), are potent synaptic modulators that are 
      expressed throughout the forebrain and play critical roles in many behavioral 
      processes. Although the effects of BDNF at excitatory synapses have been well 
      characterized, the mechanisms of action of BDNF at inhibitory synapses are not 
      well understood. Previously we have found that BDNF suppresses presynaptic GABA 
      release in layer 2/3 of the neocortex via postsynaptic tropomyosin-related kinase 
      receptor B (trkB) receptor-induced release of endocannabinoids. To examine the 
      intracellular signaling pathways that underlie this effect, we used 
      pharmacological approaches and whole cell patch-clamp techniques in layer 2/3 
      pyramidal neurons of somatosensory cortex in brain slices from juvenile Swiss CD1 
      mice. Our results indicated that phospholipase Cgamma (PLCgamma) is involved in the CB1 
      receptor-mediated synaptic effect of BDNF, because the BDNF effect was blocked in 
      the presence of the broad-spectrum PLC inhibitors U-73122 and edelfosine, whereas 
      the inactive analog U-73343 did not alter the suppressive effect of BDNF at 
      inhibitory synapses. Endocannabinoid release can also be triggered by 
      metabotropic glutamate receptor (mGluR)-mediated activation of PLCbeta, and BDNF has 
      been shown to enhance spontaneous glutamate release. An mGluR antagonist, E4CPG, 
      however, did not block the BDNF effect. In addition, the effect of BDNF was 
      independent of other signaling pathways downstream of trkB receptor activation, 
      namely, mitogen-activated protein kinase and phosphoinositide 3-kinase pathways, 
      as well as protein kinase C signaling.
FAU - Zhao, Liangfang
AU  - Zhao L
AD  - Department of Neuroscience, University of Connecticut Health Center, Farmington, 
      Connecticut.
FAU - Levine, Eric S
AU  - Levine ES
LA  - eng
GR  - R01 MH094896/MH/NIMH NIH HHS/United States
GR  - MH-094896/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131211
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cannabinoid Receptor Antagonists)
RN  - 0 (Piperidines)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 3I4FA44MAI (AM 251)
RN  - EC 3.1.4.11 (Phospholipase C beta)
RN  - EC 3.1.4.3 (Phospholipase C gamma)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Cannabinoid Receptor Antagonists/pharmacology
MH  - *Inhibitory Postsynaptic Potentials/drug effects
MH  - Mice
MH  - Neurons/drug effects/*metabolism
MH  - Phospholipase C beta/metabolism
MH  - Phospholipase C gamma/*metabolism
MH  - Piperidines/pharmacology
MH  - Pyrazoles/pharmacology
MH  - Receptor, Cannabinoid, CB1/antagonists & inhibitors/*metabolism
MH  - Somatosensory Cortex/drug effects/*metabolism
PMC - PMC3949235
OTO - NOTNLM
OT  - BDNF
OT  - cannabinoid
OT  - cerebral cortex
OT  - phospholipase C
EDAT- 2013/12/18 06:00
MHDA- 2014/10/31 06:00
PMCR- 2015/03/01
CRDT- 2013/12/17 06:00
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/10/31 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - jn.00554.2013 [pii]
AID - JN-00554-2013 [pii]
AID - 10.1152/jn.00554.2013 [doi]
PST - ppublish
SO  - J Neurophysiol. 2014 Mar;111(5):1008-15. doi: 10.1152/jn.00554.2013. Epub 2013 
      Dec 11.