PMID- 30334291
OWN - NLM
STAT- Publisher
LR  - 20240227
IS  - 1098-2396 (Electronic)
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
DP  - 2018 Oct 17
TI  - Endogenous cannabinoids mediate the effect of BDNF at CA1 inhibitory synapses in 
      the hippocampus.
PG  - e22075
LID - 10.1002/syn.22075 [doi]
AB  - Brain-derived neurotrophic factor (BDNF), traditionally known for promoting 
      neuronal growth and development, is also a modulator of synaptic transmission. In 
      addition to the well-characterized effects at excitatory synapses, BDNF has been 
      shown to acutely suppress inhibitory neurotransmission; however, the underlying 
      mechanisms are unclear. We have previously shown that at inhibitory synapses in 
      layer 2/3 of the somatosensory cortex, BDNF induces the mobilization of 
      endogenous cannabinoids (eCBs) that act retrogradely to suppress GABA release. 
      Here, we hypothesized that in the hippocampus, BDNF acts similarly via eCB 
      signaling to suppress GABAergic transmission. We found that the acute application 
      of BDNF reduced the spontaneous inhibitory postsynaptic currents (sIPSCs) via 
      postsynaptic TrkB receptor activation. The suppressive effects of BDNF required 
      eCB signaling, as this effect on sIPSCs was prevented by a CB1 receptor 
      antagonist. Further, blocking the postsynaptic eCB release prevented the effect 
      of BDNF, whereas eCB reuptake inhibition enhanced the effect of BDNF. These 
      results suggest that BDNF triggers the postsynaptic release of eCBs. To identify 
      the specific eCB release by BDNF, we tested the effects of disrupting the 
      synthesis or degradation of 2-arachidonoylcglycerol (2-AG). Blocking 2-AG 
      synthesis prevented the effect of BDNF and blocking 2-AG degradation enhanced the 
      effect of BDNF. However, there was no change in the effect of BDNF when 
      anandamide degradation was blocked. Collectively, these results suggest that in 
      the hippocampus, BDNF-TrkB signaling induces the postsynaptic release of the 
      endogenous cannabinoid 2-AG, which acts retrogradely on the presynaptic CB1 
      receptors to suppress GABA release.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Selvam, Rajamani
AU  - Selvam R
AD  - Department of Neuroscience, University of Connecticut School of Medicine, 
      Farmington, Connecticut.
FAU - Yeh, Mason L
AU  - Yeh ML
AD  - Department of Neuroscience, University of Connecticut School of Medicine, 
      Farmington, Connecticut.
FAU - Levine, Eric S
AU  - Levine ES
AUID- ORCID: 0000-0002-2535-9509
AD  - Department of Neuroscience, University of Connecticut School of Medicine, 
      Farmington, Connecticut.
LA  - eng
GR  - R01 MH094896/MH/NIMH NIH HHS/United States
GR  - R01 MH094896/National Institute of Mental Health/
PT  - Journal Article
DEP - 20181017
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
PMC - PMC6470051
MID - NIHMS1018356
OTO - NOTNLM
OT  - BDNF
OT  - CB1
OT  - TrkB
OT  - endocannabinoid
OT  - synaptic transmission
EDAT- 2018/10/20 06:00
MHDA- 2018/10/20 06:00
PMCR- 2020/04/17
CRDT- 2018/10/19 06:00
PHST- 2018/06/26 00:00 [received]
PHST- 2018/09/20 00:00 [revised]
PHST- 2018/10/12 00:00 [accepted]
PHST- 2018/10/20 06:00 [pubmed]
PHST- 2018/10/20 06:00 [medline]
PHST- 2018/10/19 06:00 [entrez]
PHST- 2020/04/17 00:00 [pmc-release]
AID - 10.1002/syn.22075 [doi]
PST - aheadofprint
SO  - Synapse. 2018 Oct 17:e22075. doi: 10.1002/syn.22075.