PMID- 28392759
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 11
DP  - 2017
TI  - Calcium-Dependent and Synapsin-Dependent Pathways for the Presynaptic Actions of 
      BDNF.
PG  - 75
LID - 10.3389/fncel.2017.00075 [doi]
LID - 75
AB  - We used cultured hippocampal neurons to determine the signaling pathways 
      mediating brain-derived neurotrophic factor (BDNF) regulation of spontaneous 
      glutamate and GABA release. BDNF treatment elevated calcium concentration in 
      presynaptic terminals; this calcium signal reached a peak within 1 min and 
      declined in the sustained presence of BDNF. This BDNF-induced transient rise in 
      presynaptic calcium was reduced by SKF96365, indicating that BDNF causes 
      presynaptic calcium influx via TRPC channels. BDNF treatment increased the 
      frequency of miniature excitatory postsynaptic currents (mEPSCs). This response 
      consisted of two components: a transient component that peaked within 1 min of 
      initiating BDNF application and a second component that was sustained, at a lower 
      mEPSC frequency, for the duration of BDNF application. The initial transient 
      component was greatly reduced by removing external calcium or by treatment with 
      SKF96365, as well as by Pyr3, a selective blocker of TRPC3 channels. In contrast, 
      the sustained component was unaffected in these conditions but was eliminated by 
      U0126, an inhibitor of the MAP kinase (MAPK) pathway, as well as by genetic 
      deletion of synapsins in neurons from a synapsin triple knock-out (TKO) mouse. 
      Thus, two pathways mediate the ability of BDNF to enhance spontaneous glutamate 
      release: the transient component arises from calcium influx through TRPC3 
      channels, while the sustained component is mediated by MAPK phosphorylation of 
      synapsins. We also examined the ability of these two BDNF-dependent pathways to 
      regulate spontaneous release of the inhibitory neurotransmitter, GABA. BDNF had 
      no effect on the frequency of spontaneous miniature inhibitory postsynaptic 
      currents (mIPSCs) in neurons from wild-type (WT) mice, but surprisingly did 
      increase mIPSC frequency in synapsin TKO mice. This covert BDNF response was 
      blocked by removal of external calcium or by treatment with SKF96365 or Pyr3, 
      indicating that it results from calcium influx mediated by TRPC3 channels. Thus, 
      the BDNF-activated calcium signaling pathway can also enhance spontaneous GABA 
      release, though this effect is suppressed by synapsins under normal physiological 
      conditions.
FAU - Cheng, Qing
AU  - Cheng Q
AD  - Department of Neurobiology, Duke University Medical Center Durham, NC, USA.
FAU - Song, Sang-Ho
AU  - Song SH
AD  - Center for Functional Connectomics, Korea Institute of Science and 
      TechnologySeoul, South Korea; Lee Kong Chian School of Medicine, Nanyang 
      Technological UniversitySingapore, Singapore; Institute of Molecular and Cell 
      BiologySingapore, Singapore.
FAU - Augustine, George J
AU  - Augustine GJ
AD  - Center for Functional Connectomics, Korea Institute of Science and 
      TechnologySeoul, South Korea; Lee Kong Chian School of Medicine, Nanyang 
      Technological UniversitySingapore, Singapore; Institute of Molecular and Cell 
      BiologySingapore, Singapore.
LA  - eng
PT  - Journal Article
DEP - 20170324
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC5364187
OTO - NOTNLM
OT  - TRP channels
OT  - neurotransmitter release
OT  - neurotrophins
OT  - synapsins
EDAT- 2017/04/11 06:00
MHDA- 2017/04/11 06:01
PMCR- 2017/01/01
CRDT- 2017/04/11 06:00
PHST- 2016/11/10 00:00 [received]
PHST- 2017/03/02 00:00 [accepted]
PHST- 2017/04/11 06:00 [entrez]
PHST- 2017/04/11 06:00 [pubmed]
PHST- 2017/04/11 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2017.00075 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2017 Mar 24;11:75. doi: 10.3389/fncel.2017.00075. 
      eCollection 2017.