PMID- 25938134
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 2373-2822 (Electronic)
IS  - 2373-2822 (Linking)
VI  - 2
IP  - 2
DP  - 2015 Feb 28
TI  - Role for Endogenous BDNF in Endocannabinoid-Mediated Long-Term Depression at 
      Neocortical Inhibitory Synapses.
LID - e0029-14.2015 [pii]
LID - ENEURO.0029-14.2015
AB  - The endogenous cannabinoid (endocannabinoid) system is an important regulator of 
      synaptic function. Endocannabinoids acutely modulate inhibitory and excitatory 
      transmission, and also mediate long-term depression at GABAergic and 
      glutamatergic synapses. Typically, endocannabinoid synthesis and release is 
      stimulated by depolarization-induced calcium influx and/or activation of 
      phospholipase-C (PLC) signaling triggered by mGluR activation. Recently it has 
      been shown that brain-derived neurotrophic factor (BDNF) can also induce 
      endocannabinoid release. Although there is growing evidence for cross-talk 
      between BDNF and endocannabinoid signaling, little is known about the functional 
      relevance of these interactions. In the present studies, we examined BDNF - 
      endocannabinoid interactions in regulating activity-dependent long-term 
      depression at inhibitory synapses (iLTD). We found that theta burst stimulation 
      (TBS) in layer 2/3 of mouse somatosensory cortical slices can induce a form of 
      endocannabinoid-mediated iLTD that is independent of metabotropic glutamate 
      receptor (mGluR) activation. This endocannabinoid-dependent iLTD, however, 
      requires endogenous BDNF-trkB signaling, as it is blocked by a trk tyrosine 
      kinase inhibitor and by a trkB receptor antagonist, and also requires activation 
      of diacylglycerol lipase (DAG-lipase, DGL). In addition, endocannabinoid-mediated 
      iLTD can be induced by combining a subthreshold concentration of exogenous BDNF 
      with weak TBS stimulation that by itself is insufficient to induce iLTD. Taken 
      together, our results suggest that TBS can induce the release of endogenous BDNF, 
      which triggers DGL-dependent endocannabinoid mobilization and cannabinoid 
      receptor-dependent iLTD at layer 2/3 cortical synapses.
FAU - Zhao, Liangfang
AU  - Zhao L
AD  - Department of Neuroscience, University of Connecticut Health Center, Farmington, 
      Connecticut 06030.
FAU - Yeh, Mason Li-Wen
AU  - Yeh ML
AD  - Department of Neuroscience, University of Connecticut Health Center, Farmington, 
      Connecticut 06030.
FAU - Levine, Eric S
AU  - Levine ES
AD  - Department of Neuroscience, University of Connecticut Health Center, Farmington, 
      Connecticut 06030.
LA  - eng
GR  - R01 MH094896/MH/NIMH NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - eNeuro
JT  - eNeuro
JID - 101647362
PMC - PMC4415885
MID - NIHMS684239
OTO - NOTNLM
OT  - BDNF
OT  - CB1
OT  - endocannabinoid
OT  - inhibitory
OT  - long-term depression
OT  - trkB
COIS- Authors report no conflict of interest.
EDAT- 2015/05/06 06:00
MHDA- 2015/05/06 06:01
PMCR- 2015/04/01
CRDT- 2015/05/05 06:00
PHST- 2015/05/05 06:00 [entrez]
PHST- 2015/05/06 06:00 [pubmed]
PHST- 2015/05/06 06:01 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - e0029-14.2015 [pii]
AID - eN-NWR-0029-14 [pii]
AID - 10.1523/ENEURO.0029-14.2015 [doi]
PST - ppublish
SO  - eNeuro. 2015 Feb 28;2(2):ENEURO.0029-14.2015. doi: 10.1523/ENEURO.0029-14.2015.